Background and ObjectivesLimb-girdle muscular dystrophy R2 (LGMDR2) is characterized by progressive muscle weakness usually leading to severe disability. The rate of progression and disease severity is variable among patients, although factors influencing this variability are not completely understood. The Dysferlinopathy Clinical Outcome Study is a natural history study that followed patients with LGMDR2 for 3 consecutive years using functional outcome measures and skeletal muscle MRI.The aim of our study was to develop statistical models able to describe fat fraction (FF) progression of the lower limbs in patients with LGMDR2 using clinical and radiologic variables to better understand which factors influence disease progression and improve the design of future clinical trials.Background and ObjectivesLimb-girdle muscular dystrophy R2 (LGMDR2) is characterized by progressive muscle weakness usually leading to severe disability. The rate of progression and disease severity is variable among patients, although factors influencing this variability are not completely understood. The Dysferlinopathy Clinical Outcome Study is a natural history study that followed patients with LGMDR2 for 3 consecutive years using functional outcome measures and skeletal muscle MRI.The aim of our study was to develop statistical models able to describe fat fraction (FF) progression of the lower limbs in patients with LGMDR2 using clinical and radiologic variables to better understand which factors influence disease progression and improve the design of future clinical trials.MethodsWe used linear-mixed modeling to analyze changes in FF over time according to patients' age. We calculated the average FF trajectory for each muscle of the lower limbs. We built 2 multivariate models for each segment adding other clinical factors and using likelihood ratio test and residuals' analysis to determine whether they better fitted observed FF values.ResultsMuscles that participated in the same joint movement progressed similarly over time. FF was expected to be higher the older patients were and the earlier the age at symptom onset. Women had absolute FF values 8.8% higher than men in the lower leg. No differences in FF trajectory were seen based on ethnic groups (White, Asian, Black, or Hispanic), genetic variants, or residual dysferlin expression. Although multivariate models showed a better global fit to the data, there was no improvement in representing individual patient variability.DiscussionIn conclusion, this study provides a better understanding of skeletal muscle fat replacement progression in the lower limb muscles of patients with LGMDR2, highlighting the influence of age at symptom onset, sex, and baseline motor function, which should be considered in the design and analysis of clinical trials. Although complex models improved the overall data fit, they did not improve the accuracy in identifying changes at a patient level, underlying the need for further research and validation and the fact that other variables we have not measured are probably influencing progression.

Walking and cycling (active travel) are an important carbon neutral means for accessing new development which improves public health and maximises the opportunities created for all of society. Across northern England’s rustbelt, local authorities seek to reinvigorate their economies, but it is presently unclear how active travel supports these efforts. This article explores these issues by evaluating how promises of active travel improvements have been taken up by planners in two contrasting local authorities in northern England; one an economically vibrant metropolitan city and the other a struggling deindustrialised town. Drawing on testimony of planners and evaluation using the delivery = context, intelligence and behaviour (D=CIB) framework, we find considerable variation in how active travel is regarded and prioritised while planners in both areas grapple with common problems on resourcing planning and design of planning instruments.

Background and Objectives:Limb-girdle muscular dystrophy R2 (LGMDR2) is characterized by progressive muscle weakness usually leading to severe disability. The rate of progression and disease severity is variable among patients, although factors influencing this variability are not completely understood. The Dysferlinopathy Clinical Outcome Study is a natural history study that followed patients with LGMDR2 for 3 consecutive years using functional outcome measures and skeletal muscle MRI.The aim of our study was to develop statistical models able to describe fat fraction (FF) progression of the lower limbs in patients with LGMDR2 using clinical and radiologic variables to better understand which factors influence disease progression and improve the design of future clinical trials. Methods:We used linear-mixed modeling to analyze changes in FF over time according to patients' age. We calculated the average FF trajectory for each muscle of the lower limbs. We built 2 multivariate models for each segment adding other clinical factors and using likelihood ratio test and residuals' analysis to determine whether they better fitted observed FF values. Results:Muscles that participated in the same joint movement progressed similarly over time. FF was expected to be higher the older patients were and the earlier the age at symptom onset. Women had absolute FF values 8.8% higher than men in the lower leg. No differences in FF trajectory were seen based on ethnic groups (White, Asian, Black, or Hispanic), genetic variants, or residual dysferlin expression. Although multivariate models showed a better global fit to the data, there was no improvement in representing individual patient variability. Discussion:In conclusion, this study provides a better understanding of skeletal muscle fat replacement progression in the lower limb muscles of patients with LGMDR2, highlighting the influence of age at symptom onset, sex, and baseline motor function, which should be considered in the design and analysis of clinical trials. Although complex models improved the overall data fit, they did not improve the accuracy in identifying changes at a patient level, underlying the need for further research and validation and the fact that other variables we have not measured are probably influencing progression.

Transportation and accessibility remain an important consideration in land use planning decision-making if modal shifts towards sustainable forms of transport are to be encouraged. Land value capture (LVC) mechanisms which gather developer contributions can provide new transport infrastructure which supports such a shift. Within England, this has traditionally been pursued through negotiated section 106 agreements, yet data suggest a significant decline in the value of these contributions for transport measures since 2010. This paper investigates the reduction to understand the reasons behind it and then considers the resulting implications for policy and LVC practices using a qualitative synthesis.

This study aims to identify two critical components required for pharmaceutical cleaning verification when an FTIR is used: (a) the number of scans required per hard-to-clean location, and (b) the limit of quantification (LOQ) of the FTIR instrument when measuring the surface contamination. The current practice in pharmaceutical manufacturing does not require multiple samples as it is standard practice to collect a single swab sample from a 25 × 25 cm area from a difficult-to-reach area of the manufacturing equipment. However, since the FTIR will only scan a tiny portion of the surface compared to the swab, a sufficient number of samples (data points) are required to provide enough confidence to ensure that the measurement results are close to the true value with a maximum degree of certainty. Similarly, calculating the LOQ for a linear regression could be straightforward. However, complexity arises when the experimental data are complex; in this case, the complexity arises due to the nature of the measurement and the lack of the defined peak in the pre-processed spectra. Therefore, this study uses the practical approach of calculating the sample size and the LOQ.

Purpose: Chemical shift-encoded MRI (CSE-MRI) is well-established to quantify proton density fat fraction (PDFF) as a quantitative biomarker of hepatic steatosis. However, temperature is known to bias PDFF estimation in phantom studies. In this study, strategies were developed and evaluated to correct for the effects of temperature on PDFF estimation through simulations, temperature-controlled experiments, and a multi-center, multi-vendor phantom study. Theory and Methods: A technical solution that assumes and automatically estimates a uniform, global temperature throughout the phantom is proposed. Computer simulations modeled the effect of temperature on PDFF estimation using magnitude-, complex-, and hybrid-based CSE-MRI methods. Phantom experiments were performed to assess the temperature correction on PDFF estimation at controlled phantom temperatures. To assess the temperature correction method on a larger scale, the proposed method was applied to data acquired as part of a nine-site multi-vendor phantom study and compared to temperature-corrected PDFF estimation using an a priori guess for ambient room temperature. Results: Simulations and temperature-controlled experiments show that as temperature deviates further from the assumed temperature, PDFF bias increases. Using the proposed correction method and a reasonable a priori guess for ambient temperature, PDFF bias and variability were reduced using magnitude-based CSE-MRI, across MRI systems, field strengths, protocols, and varying phantom temperature. Complex and hybrid methods showed little PDFF bias and variability both before and after correction. Conclusion: Correction for temperature reduces temperature-related PDFF bias and variability in phantoms across MRI vendors, sites, field strengths, and protocols for magnitude-based CSE-MRI, even without a priori information about the temperature.

Quality in MR imaging is a comprehensive process that encompasses scanner performance, clinical processes for efficient scanning and reporting, as well as data-driven improvement involving measurement of key performance indicators. In this paper, the authors review this entire process. This article provides a framework for establishing a successful MR quality program. The collective experiences of the authors across a spectrum of pediatric hospitals is summarized here.

Human norovirus (NoV) is the leading cause of foodborne illness in the United States and Canada. Bivalve molluscan shellfish is one commodity commonly identified as being a vector of NoV. Bivalve molluscan shellfish are grown in waters that may be affected by contamination events, tend to bioaccumulate viruses, and are frequently eaten raw. In an effort to better assess the elements that contribute to potential risk of NoV infection and illness from consumption of bivalve molluscan shellfish, the U.S. Department of Health and Human Services/Food and Drug Administration (FDA), Health Canada (HC), the Canadian Food Inspection Agency (CFIA), and Environment and Climate Change Canada (ECCC) collaborated to conduct a quantitative risk assessment for NoV in bivalve molluscan shellfish, notably oysters. This study describes the model and scenarios developed and results obtained to assess the risk of NoV infection and illness from consumption of raw oysters harvested from a quasi-steady-state situation. Among the many factors that influence the risk of NoV illness for raw oyster consumers, the concentrations of NoV in the influent (raw, untreated) and effluent (treated) of wastewater treatment plants (WWTP) were identified to be the most important. Thus, mitigation and control strategies that limit the influence from human waste (WWTP outfalls) in oyster growing areas have a major influence on the risk of illness from consumption of those oysters.

Noncontrast magnetic resonance imaging techniques for measuring brain perfusion include arterial spin labeling (ASL) and intravoxel incoherent motion (IVIM). These techniques provide noninvasive and repeatable assessment of cerebral blood flow or cerebral blood volume without the need for intravenous contrast. This article discusses the technical aspects of ASL and IVIM with a focus on normal physiologic variations, technical parameters, and artifacts. Multiple pediatric clinical applications are presented, including tumors, stroke, vasculopathy, vascular malformations, epilepsy, migraine, trauma, and inflammation.

Introduction MRI and MR spectroscopy (MRS) provide early biomarkers of brain injury and treatment response in neonates with hypoxic-ischaemic encephalopathy). Still, there are challenges to incorporating neuroimaging biomarkers into multisite randomised controlled trials. In this paper, we provide the rationale for incorporating MRI and MRS biomarkers into the multisite, phase III high-dose erythropoietin for asphyxia and encephalopathy (HEAL) Trial, the MRI/S protocol and describe the strategies used for harmonisation across multiple MRI platforms. Methods and analysis Neonates with moderate or severe encephalopathy enrolled in the multisite HEAL trial undergo MRI and MRS between 96 and 144 hours of age using standardised neuroimaging protocols. MRI and MRS data are processed centrally and used to determine a brain injury score and quantitative measures of lactate and n-acetylaspartate. Harmonisation is achieved through standardisation—thereby reducing intrasite and intersite variance, real-time quality assurance monitoring and phantom scans. Ethics and dissemination IRB approval was obtained at each participating site and written consent obtained from parents prior to participation in HEAL. Additional oversight is provided by an National Institutes of Health-appointed data safety monitoring board and medical monitor. Trial registration number NCT02811263; Pre-result.

There are limited MRI studies of craniofacial and velopharyngeal features in children with 22q11.2 deletion syndrome (22q11.2DS) and to date, none have explored the potential relationship between these features and the speech phenotype. The purpose of this study was to examine the relationship between craniofacial and related velopharyngeal structures in children with 22q11.2DS and to assess their correlation to resonance features using an unsedated MRI protocol.Fifteen children with 22q11.2DS and 15 age- and sex-matched controls with normal velopharyngeal anatomy (ages 4–12 years) successfully completed the study. Analysis of covariance was used to compare differences between the experimental (22q11.2DS) and control (children with normal anatomy) groups. Correlation analyses and regression models were also utilized.The 22q11.2DS group demonstrated significantly shorter nasion-to-sella, sella-to-basion, and basion-to-opisthion distances. The anterior cranial base angle was significantly more obtuse. The levator veli palatini (levator) muscle was significantly thinner and shorter, with an obtuse angle of origin in the 22q11.2DS group. Levator length was significantly correlated with the sella-to-basion measure and hypernasality was correlated with levator origin-to-origin distance. Preliminary results from this study indicate a significant association between hypernasality and levator origin-to-origin distance. Findings from the present study, provide an insight into the pathophysiology of velopharyngeal dysfunction related to this clinically complex population.

Integrating transport and land use policies is a key objective in pursuing sustainable transport strategies seeking to reduce car usage. Such integration is taxing as the two developed into separate disciplines with differing cultures. These issues come to the fore during planning execution: the implementation of sustainable transport policies through the planning system. Such implementation processes prove complex and concern fit between policy intervention and practice context. In this paper, we explore these implementation issues using an integration framework employed on a longitudinal case study of Merseyside during the twenty-first century's first decade.

ABSTRACT:Zero-echo time (ZTE) magnetic resonance imaging (MRI) is the newest in a family of MRI pulse sequences that involve ultrafast sequence readouts, permitting visualization of short-T2 tissues such as cortical bone. Inherent sequence properties enable rapid, high-resolution, quiet, and artifact-resistant imaging. ZTE can be performed as part of a "one-stop-shop" MRI examination for comprehensive evaluation of head and neck pathology. As a potential alternative to computed tomography for bone imaging, this approach could help reduce patient exposure to ionizing radiation and improve radiology resource utilization. Because ZTE is not yet widely used clinically, it is important to understand the technical limitations and pitfalls for diagnosis. Imaging cases are presented to demonstrate potential applications of ZTE for imaging of oral cavity, oropharynx, and jaw anatomy and pathology in adult and pediatric patients. Emerging studies indicate promise for future clinical implementation based on synthetic computed tomography image generation, 3D printing, and interventional applications.

Within the pharmaceutical industry, it is a regulatory requirement to ensure that pharmaceutical drug manufacturing equipment is clean prior to use.

Arterial spin labeling (ASL) is a powerful noncontrast magnetic resonance imaging (MRI) technique that enables quantitative evaluation of brain perfusion. To optimize the clinical and research utilization of ASL, radiologists and physicists must understand the technical considerations and age-related variations in normal and disease states. We discuss advanced applications of ASL across the lifespan, with example cases from children and adults covering a wide variety of pathologies. Through literature review and illustrated clinical cases, we highlight the subtleties as well as pitfalls of ASL interpretation. First, we review basic physical principles, techniques, and artifacts. This is followed by a discussion of normal perfusion variants based on age and physiology. The three major categories of perfusion abnormalities-hypoperfusion, hyperperfusion, and mixed patterns-are covered with an emphasis on clinical interpretation and relationship to the disease process. Major etiologies of hypoperfusion include large artery, small artery, and venous disease; other vascular conditions; global hypoxic-ischemic injury; and neurodegeneration. Hyperperfusion is characteristic of vascular malformations and tumors. Mixed perfusion patterns can be seen with epilepsy, migraine, trauma, infection/inflammation, and toxic-metabolic encephalopathy. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 3.

Purpose: To investigate the dimensions of the tensor veli palatini (TVP) muscle using high image resolution 3-dimensional magnetic resonance imaging (MRI) of the soft palate among children with normal velopharyngeal and craniofacial anatomy and to compare values to individuals with a diagnosis of 22q11.2 deletion syndrome (22q11DS). We also sought to determine whether there is a relationship between hypoplasia of the TVP and severity of middle ear dysfunction and hearing loss. Methods: Three-dimensional MRI were used to collect and analyze data obtained across 53 children between 4 and 12 years of age, including 40 children with normal velopharyngeal and craniofacial anatomy and 13 children with a diagnosis of 22q11.2 DS. Tensor veli palatini muscle length, thickness, and volume as well as bihamular distance were compared among participant groups. Results: A Welch’s t-test revealed that the TVP in participants with 22q11DS is significantly shorter ( P = .005, 17.3 vs 19.0 mm), thinner ( P < .001, 1.1 vs 1.8 mm), and less voluminous ( P < .001, 457.5 vs 667.3 mm 3 ) than participants without 22q11DS. Participants with 22q11DS also had a greater ( P = .006, 27.7 vs 24.7 mm) bihamular distance than participants without 22q11DS. There was an inverse relationship between TVP abnormalities noted above and the severity of audiologic and otologic histories. Conclusion: The TVP muscle is substantially reduced in volume, length, and thickness in children with 22q11DS. These findings serve as preliminary support for the association of patient hearing and otologic severity and TVP dysmorphology.

Rationale and Objectives: We describe our preliminary experience using a 2D turbo gradient- and spin-echo (TGSE) diffusion-weighted (DW) pulse sequence with non-Cartesian BLADE trajectory at 3 T in pediatric patients. We compared the TGSE BLADE to conventional DW spin-echo echo-planar imaging (SE-EPI) in pediatric brain imaging, assessing the presence of artifacts from signal pile-ups, geometric distortion, motion, susceptibility from air-tissue interface, shunts and orthodontia, and diagnostic image quality. Materials and Methods: Data were acquired in 53 patients (10.4 +/- 7.9 years). All DW imaging data were acquired precontrast, with SE-EPI first. A four-point scale for rating was used - 1 (best) and 4 (worst). A neuroradiologist scored the two sequences and further noted whether the TGSE BLADE approach or SE-EPI was preferred in each case. Apparent diffusion coefficients were compared quantitatively between the two sequences in a subset of 16 patients, in 41 separate regions of interests including caudate nucleus, putamen, globus pallidus, thalamus, and pathological areas. Results: In 43.4% of the cases, TGSE BLADE was preferred; in 49.1% of the cases, both sequences were preferred equally. Average scores for SE-EPI were 2.2 +/- 0.8 versus TGSE's 1.2 +/- 0.4 in assessing diagnostic quality (p < 0.05). Motion artifacts were minimal on both sequences in 92.5% of the cases. In the TGSE BLADE scores, no case received a "4" for significant artifacts with marginally acceptable image quality. Apparent diffusion coefficients values between the two sequences were statistically similar, with a linear regression slope of 0.92 (r(2) = 0.97). Conclusion: TGSE BLADE DW imaging exhibited less geometric distortion in the brain and reduced signal pile-ups in areas of high susceptibility than conventional SE-EPI.

ObjectiveTo assess the ability of functional measures to detect disease progression in dysferlinopathy over 6 months and 1 year.MethodsOne hundred ninety-three patients with dysferlinopathy were recruited to the Jain Foundation's International Clinical Outcome Study for Dysferlinopathy. Baseline, 6-month, and 1-year assessments included adapted North Star Ambulatory Assessment (a-NSAA), Motor Function Measure (MFM-20), timed function tests, 6-minute walk test (6MWT), Brooke scale, Jebsen test, manual muscle testing, and hand-held dynamometry. Patients also completed the ACTIVLIM questionnaire. Change in each measure over 6 months and 1 year was calculated and compared between disease severity (ambulant [mild, moderate, or severe based on a-NSAA score] or nonambulant [unable to complete a 10-meter walk]) and clinical diagnosis.ResultsThe functional a-NSAA test was the most sensitive to deterioration for ambulant patients overall. The a-NSAA score was the most sensitive test in the mild and moderate groups, while the 6MWT was most sensitive in the severe group. The 10-meter walk test was the only test showing significant change across all ambulant severity groups. In nonambulant patients, the MFM domain 3, wrist flexion strength, and pinch grip were most sensitive. Progression rates did not differ by clinical diagnosis. Power calculations determined that 46 moderately affected patients are required to determine clinical effectiveness for a hypothetical 1-year clinical trial based on the a-NSAA as a clinical endpoint.ConclusionCertain functional outcome measures can detect changes over 6 months and 1 year in dysferlinopathy and potentially be useful in monitoring progression in clinical trials.ClinicalTrials.gov identifier:NCT01676077.

MRI methods that have reduced sensitivity to motion are attractive in pediatric applications. In spine imaging, physiologic motion such as respiration and cerebrospinal fluid pulsation can hamper diagnostic image quality. We compare a 3D T1-weighted non-Cartesian radial acquisition with a conventional Cartesian 2D turbo-spin-echo (TSE) acquisition in axial post-contrast spine imaging at 3T. Thirty-two patients (mean age 12.2 ± 5.3 years) scheduled for routine clinical spine exams with contrast were enrolled. Three pediatric neuroradiologists compared the two sequences and assessed the presence of motion, the conspicuity of nerve roots, and whether one of the sequences was preferred in visualizing pathology using Likert scales. The Fleiss’ kappa statistic for inter-rater agreement was 0.29 (95% confidence interval, 0.15–0.43) for the presence of motion, 0.30 (0.21–0.38) for conspicuity, and 0.37 (0.19–0.55) for sequence preference. Radial images were less sensitive to motion than TSE (p < 0.01). Motion and consequent artifacts were present in all TSE cases, while it was absent in 51% of the radial cases. In depicting nerve roots, radial images were superior in the cervical (p < 0.05), thoracic (p < 0.01), and lumbar spines (p < 0.01). Lastly, in 28 of the 32 patients who demonstrated contrast-enhancing pathology, radial images were preferred in 51% of the cases, while both sequences were equally preferred in 41% of the cases. We demonstrate the potential utility of radial MRI in post-contrast spine imaging. The free-breathing method is robust in generating diagnostic image quality and is superior in visualizing nerve roots and extramedullary metastases than traditional Cartesian TSE acquisitions.