Self-rectifying magnetoelectric metamaterials for remote neural stimulation and motor function restoration.

Magnetoelectric materials convert magnetic fields into electric fields. These materials are often used in wireless electronic and biomedical applications. For example, magnetoelectrics could enable the remote stimulation of neural tissue, but the optimal resonance frequencies are typically too high to stimulate neural activity. Here we describe a self-rectifying magnetoelectric metamaterial for a precisely timed neural stimulation. This metamaterial relies on nonlinear charge transport across semiconductor layers that allow the material to generate a steady bias voltage in the presence of an alternating magnetic field. We generate arbitrary pulse sequences with time-averaged voltage biases in excess of 2 V. As a result, we can use magnetoelectric nonlinear metamaterials to wirelessly stimulate peripheral nerves to restore a sensory reflex in an anaesthetized rat model and restore signal propagation in a severed nerve with latencies of less than 5 ms. Overall, these results showing the rational design of magnetoelectric metamaterials support applications in advanced biotechnology and electronics.

MR-guided focused ultrasound therapy of extra-abdominal desmoid tumors: a multicenter retrospective study of 105 patients.

OBJECTIVE: To assess the safety and efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment extra-abdominal desmoids. METHODS: A total of 105 patients with desmoid fibromatosis (79 females, 26 males; 35 ± 14 years) were treated with MRgFUS between 2011 and 2021 in three centers. Total and viable tumors were evaluated per patient at last follow-up after treatment. Response and progression-free survival (PFS) were assessed with (modified) response evaluation criteria in solid tumors (RECIST v.1.1 and mRECIST). Change in Numerical Rating Scale (NRS) pain and 36-item Short Form Health Survey (SF-36) scores were compared. Treatment-related adverse events were recorded. RESULTS: The median initial tumor volume was 114 mL (IQR 314 mL). After MRgFUS, median total and viable tumor volume decreased to 51 mL (95% CI: 30-71 mL, n = 101, p < 0.0001) and 29 mL (95% CI: 17-57 mL, n = 88, p < 0.0001), respectively, at last follow-up (median: 15 months, 95% CI: 11-20 months). Based on total tumor measurements (RECIST), 86% (95% CI: 75-93%) had at least stable disease or better at last follow-up, but 50% (95% CI: 38-62%) of remaining viable nodules (mRECIST) progressed within the tumor. Median PFS was reached at 17 and 13 months for total and viable tumors, respectively. NRS decreased from 6 (IQR 3) to 3 (IQR 4) (p < 0.001). SF-36 scores improved (physical health (41 (IQR 15) to 46 (IQR 12); p = 0.05, and mental health (49 (IQR 17) to 53 (IQR 9); p = 0.02)). Complications occurred in 36%, most commonly 1st/2nd degree skin burns. CONCLUSION: MRgFUS reduced tumor volume, reduced pain, and improved quality of life in this series of 105 patients with extra-abdominal desmoid fibromatosis. CLINICAL RELEVANCE STATEMENT: Imaging-guided ablation is being increasingly used as an alternative to surgery, radiation, and medical therapy for the treatment of desmoid fibromatosis. MR-guided high-intensity focused ultrasound is an incisionless ablation technique that can be used to reduce tumor burden effectively and safely. KEY POINTS: • Desmoid fibromatosis was treated with MR-guided high-intensity focused ultrasound in 105 patients. • MR-guided focused ultrasound ablation reduced tumor volume and pain and improved quality of life. • MR-guided focused ultrasound is a treatment option for patients with extra-abdominal desmoid tumors.

Surgeon and Hospital Factors Associated With Outcomes in the New York State Database.

INTRODUCTION: We sought to explore the relationship between various surgeon-related and hospital-level characteristics and clinical outcomes among patients requiring cardiac surgery. METHODS: We searched the New York State Cardiac Data Reporting System for all coronary artery bypass grafting (CABG) and valve cases between 2015 and 2017. The data were analyzed without dichotomization. RESULTS: Among CABG/valve surgeons, case volume was positively correlated with years in practice (P = 0.002) and negatively correlated with risk-adjusted mortality ratio (P = 0.014). For CABG and CABG/valve surgeons, our results showed a negative association between teaching status and case volume (P = 0.002, P = 0.018). Among CABG surgeons, hospital teaching status and presence of cardiothoracic surgery residency were inversely associated with risk-adjusted mortality ratio (P = 0.006, P = 0.029). CONCLUSIONS: There is a complex relationship between case volume, teaching status, and surgical outcomes suggesting that balance between academics and volume is needed.

Technical Note: Assessment of Pulse Pileup on Single-Energy and Multienergy Images From a Clinical Photon-Counting Detector Computed Tomography.

OBJECTIVE: Pulse pileup effects occur when pulses occur so close together that they fall on top of one another, resulting in count loss and errors in energy thresholding. To date, there has been little work systematically detailing the quantitative effects of pulse pileup on material decomposition accuracy for photon-counting detector (PCD) computed tomography (CT). Our aim in this work was to quantify the effects of pulse pileup on single-energy and multienergy CT images, including low-energy bin (BL), high-energy bin (BH), iodine map, and virtual noncontrast images from a commercial PCD-CT. METHODS: Scans of a 20-cm diameter multienergy CT phantom with 10 solid inserts were acquired at a fixed tube potential as the tube current was varied across the available range. Four types of images (BL, BH, iodine map, and virtual noncontrast) were reconstructed using an iterative reconstruction algorithm at strength 2, a quantitative reconstruction kernel (Qr40), 2-/1-mm slice thickness/increment, and a 210-mm field-of-view. The mean and standard deviation of CT numbers were recorded and the ratios of CT number between BL and BH images were calculated and plotted, along with noise versus tube current and noise × versus tube current. RESULTS: As tube current was increased, the range of variations in CT numbers was less than 13.4 HU for all inserts and image types evaluated. Noise × versus tube current showed a small positive slope equal to a noise increase from 100 mA of 10% at 500 mA and 15% at 900 mA compared with what would be expected if the slope was zero. CONCLUSIONS: Minimal impact on single-energy and multienergy CT numbers and noise performance was observed for the evaluated clinical PCD-CT system.

Degenerative medial and lateral menisci root tears: demographics, clinical presentation, imaging features, and associated findings.

PURPOSE: (I) Characterize the demographics and clinical features of patients with meniscal root tears (MRT); (II) analyze the morphology, extent, and grade of MRT on MRI; (III) evaluate associated abnormalities on imaging; and (IV) evaluate the associations between imaging findings, demographics, clinical features, and joint structural abnormalities. MATERIAL AND METHODS: A search was performed to identify meniscal root tears. Age, sex, BMI, and pain were recorded. Knee radiographs and MRI were reviewed. Presence, grade and morphology of MRT, meniscal extrusion, insufficiency fractures, as well as joint structural abnormalities were scored. For goals (I), (II), and (III), tabulations for categorical variables and mean for continuous variables were computed. MRT findings variables were described using percentages. For goal (IV), adjusted linear and logistic regression were employed. RESULTS: Ninety-six patients with a mean age of 56.6 years (69 females) and mean BMI of 28.9 kg/m2 were included; 88 of the MRT were located at the posterior horn of the medial meniscus (PHMM), and 82% were radial tear. The mean tear diameter was 3.8 mm, and 78/96 tears presented with meniscal extrusion. Nineteen patients presented with subchondral insufficiency fracture (SIF), which was significantly associated with the gap of the tear (p = 0.001) and grade of the meniscal root lesion (p = 0.005). CONCLUSION: MRT typically found in middle-aged to older overweight and obese women. Lesions were mostly radial tears and located at PHMM and were frequently associated with meniscal extrusion and SIF. Moreover, the presence of SIF was significantly associated with the gap width and grade of root tear.

Deep Learning to Predict Neonatal and Infant Brain Age from Myelination on Brain MRI Scans.

Background Assessment of appropriate brain myelination on T1- and T2-weighted MRI scans is based on gestationally corrected age (GCA) and requires subjective visual inspection of the brain with knowledge of normal myelination milestones. Purpose To develop a convolutional neural network (CNN) capable of estimating neonatal and infant GCA based on brain myelination on MRI scans. Materials and methods In this retrospective study from one academic medical center, brain MRI scans of patients aged 0-25 months with reported normal myelination were consecutively collected between January 1995 and June 2019. The GCA at MRI was manually calculated. After exclusion criteria were applied, T1- and T2-weighted MRI scans were preprocessed with skull stripping, linear registration, z scoring for normalization, and downsampling. A three-dimensional regression CNN was trained to predict GCA using mean absolute error (MAE) as its loss function. Attention maps were calculated using layer-wise relevance propagation. Models were validated on an external test set from the National Institutes of Health (NIH). Model MAEs were compared using Kruskal-Wallis and Mann-Whitney tests. Results A total of 518 neonates and infants (mean GCA, 67 weeks ± 33 [SD], 56% male) was included, comprising 469 T1-, 438 T2-, and 389 T1- and T2-weighted studies. Across 10 runs, MAEs of T1-, T2-, and T1- and T2-weighted networks were 9.8 ± 2.3, 9.1 ± 1.9, and 7.7 ± 1.7 weeks, respectively. Attention map analysis demonstrated increased network attention to the cerebellum, posterior white matter, and basal ganglia signal in neonates with GCA of less than 40 weeks and the anterior white matter signal in infants with GCA of more than 120 weeks, corresponding to the known progression of myelination. The T1- and T2-weighted network tested on the external NIH test set had an MAE of 9.1 weeks, which was reduced to 5.9 weeks with further training using half the external test set (P < .001). Conclusion A three-dimensional convolutional neural network can predict the gestationally corrected age of neonates and infants aged 0-25 months based on brain myelination patterns on T1- and T2-weighted MRI scans. © RSNA, 2022 Online supplemental material is available for this article.

Magnetoelectric Bio-Implants Powered and Programmed by a Single Transmitter for Coordinated Multisite Stimulation.

This paper presents a hardware platform including stimulating implants wirelessly powered and controlled by a shared transmitter for coordinated leadless multisite stimulation. The adopted novel single-transmitter, multiple-implant structure can flexibly deploy stimuli, improve system efficiency, easily scale stimulating channel quantity and relieve efforts in device synchronization. In the proposed system, a wireless link leveraging magnetoelectric effects is co-designed with a robust and efficient system-on-chip to enable reliable operation and individual programming of every implant. Each implant integrates a 0.8-mm2 chip, a 6-mm2 magnetoelectric film, and an energy storage capacitor within a 6.2-mm3 size. Magnetoelectric power transfer is capable of safely transmitting milliwatt power to devices placed several centimeters away from the transmitter coil, maintaining good efficiency with size constraints and tolerating 60-degree, 1.5-cm misalignment in angular and lateral movement. The SoC robustly operates with 2-V source amplitude variations that spans a 40-mm transmitter-implant distance change, realizes individual addressability through physical unclonable function IDs, and achieves 90% efficiency for 1.5-to-3.5-V stimulation with fully programmable stimulation parameters.

Cervical Lymph Node Features Predictive of Suboptimal Adequacy During Ultrasound-Guided Fine-Needle Aspiration in Thyroid Cancer Patients.

PURPOSE: To determine the rate of cytologic and diagnostic adequacy and identify features associated with suboptimal tissue sampling in ultrasound-guided fine-needle aspiration (US-FNA) of suspected nodal disease in thyroid cancer patients. METHODS: A single-institution pathology database was queried for lymph node FNA reports in thyroid cancer patients from 2014 to 2019. Charts were reviewed for demographics, body mass index (BMI), prior thyroidectomy, cancer type, and subsequent surgery. Ultrasound images were retrospectively reviewed for location, size, depth from skin, cystic components, macrocalcification, echogenic foci, and internal vascularity score. Pathology reports were categorized as cellular and diagnostic, hypocellular/acellular but diagnostic with abnormal cells or thyroglobulin levels, or hypocellular and nondiagnostic. Correlation and multivariate regression analyses were performed. RESULTS: Initial query yielded 552 lesions in 343 subjects. Following exclusion, 377 lesions in 255 subjects were included. Mean patient age was 48.5 years (14-90), BMI 28.5, and 66.7% female and 33.3% male. The majority (95.3%) had papillary thyroid carcinoma (PTC); and 65.5% had prior thyroidectomy. 17.7% of lesions were hypocellular/acellular (suboptimal), and 5.6% nondiagnostic. Patient factors had no association (P >.05). Right-sidedness and hypovascularity were associated with hypocellularity (P <.05). Higher long/short-axis ratio and cystic foci were weakly associated. On multivariate analysis, right-sidedness (odds ratio [OR] 1.99; confidence interval [CI] 1.10-3.57) and lower vascularity score (OR 0.54; CI 0.39-0.73) were predictive of suboptimal sampling. CONCLUSION: US-FNA has high diagnostic yield and cellular sample rate. Lesion size had no effect. Right-sidedness and lower vascularity scores were predictive of suboptimal tissue. Identifying these features and expected sample adequacy rates can inform management decisions for thyroid cancer patients with cervical lymphadenopathy.

Diagnosis of acute mesenteric ischemia assisted by dual-energy CT: a case report.

In this case report, dual-energy CT was critical in the diagnosis of acute mesenteric ischemia by differentiating normal contrast-enhanced bowel and hemorrhagic necrosis. Iodine map showed a segment of small bowel with minimal contrast enhancement, and virtual non-contrast imaging revealed hyperattenuating bowel. This finding changed management for the patient and prevented complications from impending bowel perforation. Histopathological analysis confirmed hemorrhagic necrosis of the bowel segment. In cases of suspected bowel ischemia, dual-energy CT can distinguish bowel wall hemorrhage from contrast enhancement and allow for accurate diagnosis.

Multi-institutional Experience with Patient Image Access Through Electronic Health Record Patient Portals.

The objective is to determine patients' utilization rate of radiology image viewing through an online patient portal and to understand its impact on radiologists. IRB approval was waived. In this two-part, multi-institutional study, patients' image viewing rate was retrospectively assessed, and radiologists were anonymously surveyed for the impact of patient imaging access on their workflow. Patient access to web-based image viewing via electronic patient portals was enabled at 3 institutions (all had open radiology reports) within the past 5 years. The number of exams viewed online was compared against the total number of viewable imaging studies. An anonymized survey was distributed to radiologists at the 3 institutions, and responses were collected over 2 months. Patients viewed 14.2% of available exams - monthly open rate varied from 7.3 to 41.0%. A total of 254 radiologists responded to the survey (response rate 32.8%); 204 were aware that patients could view images. The majority (155/204; 76.0%) felt no impact on their role as radiologists; 11.8% felt negative and 9.3% positive. The majority (63.8%) were never approached by patients. Of the 86 who were contacted, 46.5% were contacted once or twice, 46.5% 3-4 times a year, and 4.7% 3-4 times a month. Free text comments included support for healthcare transparency (71), concern for patient confusion and anxiety (45), and need for attention to radiology reports and image annotations (15). A small proportion of patients viewed their radiology images. Overall, patients' image viewing had minimal impact on radiologists. Radiologists were seldom contacted by patients. While many radiologists feel supportive, some are concerned about causing patient confusion and suggest minor workflow modifications.

Does the Type of MRI Sequence Influence Perceived Quality and Measurement Consistency in Investigations of the Anatomy of the Velopharynx?

PURPOSE: The purpose of this study was to evaluate perceived image quality, confidence in identifying key velopharyngeal landmarks, and reliability of making velopharyngeal measures between 3-dimensional (3-D) and 2-D magnetic resonance imaging (MRI) methods and between T1-, T2-, and proton density (PD)-weighted sequences. METHODS: Twelve healthy participants completed an MRI study. Three raters assessed overall image quality and their ability to identify key anatomic features within the images. A single rater evaluated the reliability of making measures between imaging methods and sequence types to determine if image type (2-D and 3-D) or image sequence (T1, T2, PD weighted) resulted in different values for key velopharyngeal landmarks. RESULTS: An analysis of variance test revealed image quality was rated significantly different based on the scan type (P < .001) and the sequence used (P = .015). Image quality was rated higher among 2-D MR images compared to 3-D, and higher among T2 sequences compared to T1- and PD-weighted imaging methods. In contrast, raters favored 3-D sequences over 2-D sequences for identifying velopharyngeal landmarks. Measures of reliability revealed scan type significantly impacted 2 of the 6 variables but to a minimal degree; however, sequence type had no impact on measures of reliability across all variables. CONCLUSION: Results of the study suggest the scan type and sequence used are factors that likely do not impact the reliability of measures. Based on image quality, the recommended technique for velopharyngeal imaging would be using a 2-D T2-weighted technique. However, based on the ability to identify key landmarks, a 3-D T1- or PD-weighted technique was favored.

Distributed sensor and actuator networks for closed-loop bioelectronic medicine.

Designing implantable bioelectronic systems that continuously monitor physiological functions and simultaneously provide personalized therapeutic solutions for patients remains a persistent challenge across many applications ranging from neural systems to bioelectronic organs. Closed-loop systems typically consist of three functional blocks, namely, sensors, signal processors and actuators. An effective system, that can provide the necessary therapeutics, tailored to individual physiological factors requires a distributed network of sensors and actuators. While significant progress has been made, closed-loop systems still face many challenges before they can truly be considered as long-term solutions for many diseases. In this review, we consider three important criteria where materials play a critical role to enable implantable closed-loop systems: Specificity, Biocompatibility and Connectivity. We look at the progress made in each of these fields with respect to a specific application and outline the challenges in creating bioelectronic technologies for the future.

Engineering adjustable two-pore devices for parallel ion transport and DNA translocations.

We report ionic current and double-stranded DNA (dsDNA) translocation measurements through solid-state membranes with two TEM-drilled ∼3-nm diameter silicon nitride nanopores in parallel. Nanopores are fabricated with similar diameters but varying in effective thicknesses (from 2.6 to 10 nm) ranging from a thickness ratio of 1:1 to 1:3.75, producing distinct conductance levels. This was made possible by locally thinning the silicon nitride membrane to shape the desired topography with nanoscale precision using electron beam lithography (EBL). Two nanopores are engineered and subsequently drilled in either the EBL-thinned or the surrounding membrane region. By designing the interpore separation a few orders of magnitude larger than the pore diameter (e.g., ∼900 vs 3 nm), we show analytically, numerically, and experimentally that the total conductance of the two pores is the sum of the individual pore conductances. For a two-pore device with similar diameters yet thicknesses in the ratio of 1:3, a ratio of ∼1:2.2 in open-pore conductances and translocation current signals is expected, as if they were measured independently. Introducing dsDNA as analytes to both pores simultaneously, we detect more than 12 000 events within 2 min and trace them back with a high likelihood to which pore the dsDNA translocated through. Moreover, we monitor translocations through one active pore only when the other pore is clogged. This work demonstrates how two-pore devices can fundamentally open up a parallel translocation reading system for solid-state nanopores. This approach could be creatively generalized to more pores with desired parameters given a sufficient signal-to-noise ratio.

Morphology of the Musculus Uvulae In Vivo Using MRI and 3D Modeling Among Adults With Normal Anatomy and Preliminary Comparisons to Cleft Palate Anatomy.

PURPOSE: To investigate the musculus uvulae morphology in vivo in adults with normal velopharyngeal anatomy and to examine sex and race effects on the muscle morphology. We also sought to provide a preliminary comparison of musculus uvulae morphology in adults with normal velopharyngeal anatomy to adults with repaired cleft palate. METHODS: Three-dimensional magnetic resonance imaging data and Amira 5.5 Visualization Modeling software were used to evaluate the musculus uvulae in 70 participants without cleft palate and 6 participants with cleft palate. Muscle length, thickness, width, and volume were compared among participant groups. RESULTS: Analysis of covariance analysis did not yield statistically significant differences in musculus uvulae length, thickness, width, or volume by race or sex among participants without cleft palate when the effect of body size was accounted for. Two-sample t test revealed that the musculus uvulae in participants with repaired cleft palate is significantly shorter (P = .008, 13.65 mm vs 16.07 mm) and has less volume (P = .002, 51.08 mm3 vs 97.62 mm3) than participants without cleft palate. CONCLUSION: In adults with normal velopharyngeal anatomy, the musculus uvulae is a cylindrical oblong-shaped muscle lying on the nasal surface of the soft palate, with its greatest bulk located just nasal to the levator veli palatini muscle sling. In participants with repaired cleft palate, the musculus uvulae is substantially reduced in volume. This diminished muscle bulk located just at the point where the palate contacts the posterior pharyngeal wall may contribute to velopharyngeal insufficiency in children with repaired cleft palate.

A 9-valent HPV vaccine against infection and intraepithelial neoplasia in women.

BACKGROUND: The investigational 9-valent viruslike particle vaccine against human papillomavirus (HPV) includes the HPV types in the quadrivalent HPV (qHPV) vaccine (6, 11, 16, and 18) and five additional oncogenic types (31, 33, 45, 52, and 58). Here we present the results of a study of the efficacy and immunogenicity of the 9vHPV vaccine in women 16 to 26 years of age. METHODS: We performed a randomized, international, double-blind, phase 2b-3 study of the 9vHPV vaccine in 14,215 women. Participants received the 9vHPV vaccine or the qHPV vaccine in a series of three intramuscular injections on day 1 and at months 2 and 6. Serum was collected for analysis of antibody responses. Swabs of labial, vulvar, perineal, perianal, endocervical, and ectocervical tissue were obtained and used for HPV DNA testing, and liquid-based cytologic testing (Papanicolaou testing) was performed regularly. Tissue obtained by means of biopsy or as part of definitive therapy (including a loop electrosurgical excision procedure and conization) was tested for HPV. RESULTS: The rate of high-grade cervical, vulvar, or vaginal disease irrespective of HPV type (i.e., disease caused by HPV types included in the 9vHPV vaccine and those not included) in the modified intention-to-treat population (which included participants with and those without prevalent infection or disease) was 14.0 per 1000 person-years in both vaccine groups. The rate of high-grade cervical, vulvar, or vaginal disease related to HPV-31, 33, 45, 52, and 58 in a prespecified per-protocol efficacy population (susceptible population) was 0.1 per 1000 person-years in the 9vHPV group and 1.6 per 1000 person-years in the qHPV group (efficacy of the 9vHPV vaccine, 96.7%; 95% confidence interval, 80.9 to 99.8). Antibody responses to HPV-6, 11, 16, and 18 were noninferior to those generated by the qHPV vaccine. Adverse events related to injection site were more common in the 9vHPV group than in the qHPV group. CONCLUSIONS: The 9vHPV vaccine prevented infection and disease related to HPV-31, 33, 45, 52, and 58 in a susceptible population and generated an antibody response to HPV-6, 11, 16, and 18 that was noninferior to that generated by the qHPV vaccine. The 9vHPV vaccine did not prevent infection and disease related to HPV types beyond the nine types covered by the vaccine. (Funded by Merck; ClinicalTrials.gov number, NCT00543543).

Viral and bacterial upper respiratory tract infection in hospital health care workers over time and association with symptoms.

BACKGROUND: Bacterial colonisation of the respiratory tract is commonly described and usually thought to be of no clinical significance. The aim of this study was to examine the presence and significance of bacteria and viruses in the upper respiratory tract of healthcare workers (HCWs), and association with respiratory symptoms. METHODS: A prospective cohort study was conducted in China and 223 HCWs were recruited from fever clinics and respiratory, paediatric, emergency/Intensive medication wards. Participants were followed over 4 weeks (7th May 2015 to 4th June 2015) for development of clinical respiratory illness (CRI). Nasopharyngeal swabs were obtained at baseline and at the end of the study. The primary endpoints were laboratory-confirmed bacterial colonisation and viral respiratory infection. Rates of the following infections in symptomatic and asymptomatic participants were compared at the start or end of the study; 1) all bacterial/viral infections, 2) bacterial infection and bacterial-viral co-infections, excluding virus only infections, and 3) only bacterial infections. RESULTS: Bacterial colonisation was identified in 88% (196/223) of participants at the start or end of the study. Among these participants, 66% (148/223) had only bacterial colonisation while 22% (48/223) had co-infection with a virus. Bacteria were isolated from 170 (76.2%) participants at baseline and 127 (57%) participants at the end of the study. Laboratory confirmed viral infections were identified in 53 (23.8%) participants - 35 (15.7%) at the baseline and 20 (9.0%) at the end of the study. CRI symptoms were recorded in 12 participants (4.5%) and all had a positive bacterium isolation at baseline (n = 11) or end of the study (n = 1). Among asymptomatic participants, 187 (87%) had bacterial colonisation or bacterial/viral co-infection at baseline or end of the study. Viruses were also isolated from 5 (2.4%) asymptomatic cases. Rates of all infection outcomes were higher in symptomatic participants, however differences were not statistically significant. CONCLUSION: We isolated high rates of bacteria and viruses in the upper respiratory tract of hospital HCWs, which may reflect greater exposure to respiratory infections in the hospital. Although respiratory infections are mostly symptomatic, the association between bacterial colonization and symptomatic illness is not clear. In the healthcare setting, HCWs may acquire and transmit infection to patients and other HCWs around them. Larger studies are required to explore ongoing occupational risk of respiratory infection in hospitals HCWs.

Evaluation of local treatment effect by borrowing information from similar countries in multi-regional clinical trials.

One key objective of a multi-regional clinical trial (MRCT) is to quantify country-specific treatment effects to support local registration. Naïve estimate of the treatment effects based on country-specific subsets of data are inefficient because of relatively sparse country-specific sample sizes, even in large MRCTs, and subject to many limitations. The recently developed shrinkage estimate approach improves efficiency by incorporating data from other countries but treating all other countries equally, thus ignoring similarity to the country of interest. Ideally, for the estimation of treatment effect in a country of interest, it is more efficient to use all relevant data such as that from countries that are similar to the one of interest. We propose a tree-based approach to incorporate similarity, with branches or forks used to represent the relationship of treatment effects between countries. Similarity in certain characteristics among countries in either continuous scale or categorical scale is used to build the tree. By allowing local treatment effects for countries to be random effects and follow a Gaussian process along the tree, we demonstrate that countries sharing the same internal parent nodes are more correlated and a country borrows more information from the neighbors sharing the same parent node. We illustrated this statistical framework using a MRCT with a continuous endpoint.

Accuracy of multiecho magnitude-based MRI (M-MRI) for estimation of hepatic proton density fat fraction (PDFF) in children.

PURPOSE: To assess accuracy of magnitude-based magnetic resonance imaging (M-MRI) in children to estimate hepatic proton density fat fraction (PDFF) using two to six echoes, with magnetic resonance spectroscopy (MRS) -measured PDFF as a reference standard. METHODS: This was an IRB-approved, HIPAA-compliant, single-center, cross-sectional, retrospective analysis of data collected prospectively between 2008 and 2013 in children with known or suspected nonalcoholic fatty liver disease (NAFLD). Two hundred eighty-six children (8-20 [mean 14.2 ± 2.5] years; 182 boys) underwent same-day MRS and M-MRI. Unenhanced two-dimensional axial spoiled gradient-recalled-echo images at six echo times were obtained at 3T after a single low-flip-angle (10°) excitation with ≥ 120-ms recovery time. Hepatic PDFF was estimated using the first two, three, four, five, and all six echoes. For each number of echoes, accuracy of M-MRI to estimate PDFF was assessed by linear regression with MRS-PDFF as reference standard. Accuracy metrics were regression intercept, slope, average bias, and R(2) . RESULTS: MRS-PDFF ranged from 0.2-40.4% (mean 13.1 ± 9.8%). Using three to six echoes, regression intercept, slope, and average bias were 0.46-0.96%, 0.99-1.01, and 0.57-0.89%, respectively. Using two echoes, these values were 2.98%, 0.97, and 2.72%, respectively. R(2) ranged 0.98-0.99 for all methods. CONCLUSION: Using three to six echoes, M-MRI has high accuracy for hepatic PDFF estimation in children.

Cross-sectional and longitudinal evaluation of liver volume and total liver fat burden in adults with nonalcoholic steatohepatitis.

PURPOSE: To explore the cross-sectional and longitudinal relationships between fractional liver fat content, liver volume, and total liver fat burden. METHODS: In 43 adults with non-alcoholic steatohepatitis participating in a clinical trial, liver volume was estimated by segmentation of magnitude-based low-flip-angle multiecho GRE images. The liver mean proton density fat fraction (PDFF) was calculated. The total liver fat index (TLFI) was estimated as the product of liver mean PDFF and liver volume. Linear regression analyses were performed. RESULTS: Cross-sectional analyses revealed statistically significant relationships between TLFI and liver mean PDFF (R 2 = 0.740 baseline/0.791 follow-up, P < 0.001 baseline/P < 0.001 follow-up), and between TLFI and liver volume (R 2 = 0.352/0.452, P < 0.001/< 0.001). Longitudinal analyses revealed statistically significant relationships between liver volume change and liver mean PDFF change (R 2 = 0.556, P < 0.001), between TLFI change and liver mean PDFF change (R 2 = 0.920, P < 0.001), and between TLFI change and liver volume change (R 2 = 0.735, P < 0.001). CONCLUSION: Liver segmentation in combination with MRI-based PDFF estimation may be used to monitor liver volume, liver mean PDFF, and TLFI in a clinical trial.