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Background Despite a better understanding of the epidemiology, pathogenesis, and management of patients with anaphylaxis, there remain knowledge gaps. Enumerating and prioritizing these gaps would allow limited scientific resources to be directed more effectively. Objective We sought to systematically describe and appraise anaphylaxis knowledge gaps and future research priorities based on their potential impact and feasibility. Methods We convened a 25-member multidisciplinary panel of anaphylaxis experts. Panelists formulated knowledge gaps/research priority statements in an anonymous electronic survey. Four anaphylaxis themed writing groups were formed to refine statements: (1) Population Science, (2) Basic and Translational Sciences, (3) Emergency Department Care/Acute Management, and (4) Long-Term Management Strategies and Prevention. Revised statements were incorporated into an anonymous electronic survey, and panelists were asked to rate the impact and feasibility of addressing statements on a continuous 0 to 100 scale. Results The panel generated 98 statements across the 4 anaphylaxis themes: Population Science (29), Basic and Translational Sciences (27), Emergency Department Care/Acute Management (24), and Long-Term Management Strategies and Prevention (18). Median scores for impact and feasibility ranged from 50.0 to 95.0 and from 40.0 to 90.0, respectively. Key statements based on median rating for impact/feasibility included the need to refine anaphylaxis diagnostic criteria, identify reliable diagnostic, predictive, and prognostic anaphylaxis bioassays, develop clinical prediction models to standardize postanaphylaxis observation periods and hospitalization criteria, and determine immunotherapy best practices. Conclusions We identified and systematically appraised anaphylaxis knowledge gaps and future research priorities. This study reinforces the need to harmonize scientific pursuits to optimize the outcomes of patients with and at risk of anaphylaxis.

OBJECTIVES Contemporary lower-field magnetic resonance imaging (MRI) may offer advantages for lung imaging by virtue of the improved field homogeneity. The aim of this study was to evaluate the utility of lower-field MRI for combined morphologic imaging and regional lung function assessment. We evaluate low-field MRI in patients with lymphangioleiomyomatosis (LAM), a rare lung disease associated with parenchymal cysts and respiratory failure. MATERIALS AND METHODS We performed lung imaging on a prototype low-field (0.55 T) MRI system in 65 patients with LAM. T2-weighted imaging was used for assessment of lung morphology and to derive cyst scores, the percent of lung parenchyma occupied by cysts. Regional lung function was assessed using oxygen-enhanced MRI with breath-held ultrashort echo time imaging and inhaled 100% oxygen as a T1-shortening MR contrast agent. Measurements of percent signal enhancement from oxygen inhalation and percentage of lung with low oxygen enhancement, indicating functional deficits, were correlated with global pulmonary function test measurements taken within 2 days. RESULTS We were able to image cystic abnormalities using T2-weighted MRI in this patient population and calculate cyst score with strong correlation to computed tomography measurements (R = 0.86, P < 0.0001). Oxygen-enhancement maps demonstrated regional deficits in lung function of patients with LAM. Heterogeneity of oxygen enhancement between cysts was observed within individual patients. The percent low-enhancement regions showed modest, but significant, correlation with FEV1 (R = -0.37, P = 0.007), FEV1/FVC (R = -0.33, P = 0.02), and cyst score (R = 0.40, P = 0.02). The measured arterial blood ΔT1 between normoxia and hyperoxia, used as a surrogate for dissolved oxygen in blood, correlated with DLCO (R = -0.28, P = 0.03). CONCLUSIONS Using high-performance 0.55 T MRI, we were able to perform simultaneous imaging of pulmonary structure and regional function in patients with LAM.

Pathogenic biallelic variants in POL3RA have been associated with different disorders characterized by progressive neurological deterioration. These include the 4H leukodystrophy syndrome (hypomyelination, hypogonadotropic hypogonadism, and hypodontia) and adolescent-onset progressive spastic ataxia, as well as Wiedemann-Rautenstrauch syndrome (WRS), a recognizable neonatal progeroid syndrome. The phenotypic differences between these disorders are thought to occur mainly due to different functional effects of underlying POLR3A variants. Here we present the detailed clinical course of a 37-year-old woman in whom we identified a homozygous synonymous POLR3A variant c.3336G>A resulting in leaky splicing r.[3336ins192, =, 3243_3336del94]. She presented at birth with intrauterine growth retardation, lipodystrophy, muscular hypotonia, and several WRS-like facial features, albeit without sparse hair and prominent scalp veins. She had no signs of developmental delay or intellectual disability. Over the years, above characteristic facial features, she showed severe postnatal growth retardation, global lipodystrophy, joint contractures, thoracic hypoplasia, scoliosis, anodontia, spastic quadriplegia, bilateral hearing loss, aphonia, hypogonadotropic hypogonadism, and cerebellar peduncles hyperintensities in brain imaging. These manifestations partially overlap the clinical features of the previously reported POLR3A-associated disorders, mostly mimicking the WRS. Thus, our study expands the POLR3A-mediated phenotypic spectrum and suggests existence of a phenotypic continuum underlying biallelic POLR3A variants.

BACKGROUND In Australia, using non-invasive prenatal testing (NIPT) to screen for fetal abnormalities is becoming more commonplace. However, there is a lack of standardised procedures surrounding pre-test counselling. This holds the potential for variability in pregnant people's experiences when undergoing NIPT, which subsequently may impact their ability to make informed decisions surrounding NIPT results. AIM This study sought to characterise the experiences of Australian women undergoing NIPT, including perceptions of informed choice, counselling experiences and decision to undergo NIPT. MATERIALS AND METHODS Australian women who had been recently pregnant (n = 94) completed an online survey which assessed: their knowledge of and attitude toward NIPT; satisfaction with counselling; satisfaction with their decision; and decisional conflict to undergo NIPT. The survey also allowed participants to provide qualitative information about their counselling experience and reasons for undergoing NIPT. RESULTS Overall, participants had good knowledge of and positive attitudes toward NIPT, experienced low decisional conflict and were overall satisfied with their counselling experience and decision to undergo NIPT. However, some participants expressed dissatisfaction with the lack of information provided, and biased language, by counselling providers. The desire to be informed was the most frequent reason for undergoing NIPT. CONCLUSION The provision of accurate and objective information in pre-test counselling is important to reduce decisional conflict and improve satisfaction with the decision to undergo NIPT. It is recommended counselling providers present pregnant people with neutral, objective, and accurate information at the time of pre-test counselling.

This study aimed to identify characteristics and movement-based tests that predict upper quadrant musculoskeletal injury (UQI) in military personnel over a 12-month follow-up.A prospective observational cohort study of military members (n = 494; 91.9% male) was conducted. Baseline predictors associated with UQI were gathered through surveys and movement-based tests. Survey data included demographic information, injury history, and biosocial factors. Movement-based tests include the following: Y Balance Tests (YBT), Functional Movement Screen, Selective Functional Movement Assessment lumbar multisegmental mobility, modified-modified Schober, side bridge, ankle mobility, modified Sorensen, and passive lumbar extension. Self-reported UQI was collected through monthly online surveys, and 87% completed the follow-up. Univariate associations were determined between potential predictors and UQI. A forward, stepwise logistic regression model was used to identify the best combination of predictors for UQI.Twenty-seven had UQI. Univariate associations existed with three demographic (smoking,1 previous UQI, baseline upper quadrant function ≤90%), three pain-related (Selective Functional Movement Assessment rotation, side bridge, hurdle step), and six movement-based variables (YBT upper quarter (UQ) superolateral worst score ≤57.75 cm, YBT-UQ composite worst score ≤81.1%, failed shoulder clearance, Sorenson72.14 s, in-line lunge total score15, and in-line lunge asymmetry1). Smoking, baseline upper quadrant function ≤90%, and YBT-UQ composite score ≤81.1% predicted UQI in the logistic regression while controlling for age and sex. Presenting two or more predictors resulted in good specificity (85.6%; odds ratio, 4.8; 95% confidence interval, 2.2-10.8), and at least one predictor resulted in 81.5% sensitivity (odds ratio, 3.2; 95% confidence interval, 1.2-8.7).A modifiable movement-based test (YBT-UQ), perceived upper limb function, and smoking predicted UQI. A specific (two or more) and sensitive (at least one predictor) model could identify persons at higher risk.

Background The Food Allergy Quality-of-Life Questionnaire-Parent Form (FAQLQ-PF) is widely used to assess food allergy-specific health-related quality of life (FAQL), but cannot be used directly in cost-utility analyses, which require health state utility (HSU) scores. Currently, limited evidence is available regarding the HSU of food-allergic children/adolescents. This study aimed to develop mapping algorithms from the FAQLQ-PF onto HSU scores generated by generic, preference-based, health-related quality-of-life (HRQL) instruments. Methods Caregivers of children aged 7 to 17 years with a clinician diagnosis of IgE-mediated food allergy, recruited via Allergy & Anaphylaxis Australia, completed an online FAQLQ-PF questionnaire and proxy generic preference-based pediatric instruments (Assessment of Quality of Life [AQoL]-6D and Child Health Utility 9D [CHU9D]). Optimal statistical methods were based on series of goodness-of-fit statistics. Results Mean FAQLQ-PF total score, AQoL-6D, and CHU9D utility scores of 238 food-allergic children/adolescents were 3.49 (SD: 1.41), 0.78 (SD: 0.22), and 0.74 (SD: 0.22), respectively. The Spearman correlation coefficients of FAQLQ-PF with AQoL-6D and CHU9D were rho = -0.56 and rho = -0.45, respectively. Optimal mapping algorithms were generated from selected FAQLQ-PF items, mapped onto AQoL-6D or CHU9D utility scores, with AQoL-6D demonstrating better performance. Conclusions This study generated mapping algorithms to help facilitate the use of FAQLQ-PF for cost-utility analyses, which are essential for health economic evaluation. External validation of the reported mapping algorithms is warranted.

In recent years, two-dimensional (2D) finite element modeling (FEM) has been used to explore how the structural integrity of a corrugated metal pipe (CMP) culvert is affected by simulation of its constituent components (i.e., the pipe metal, surrounding soil, or both). However, under various conditions, the nature of the problem is three-dimensional (3D) and 2D simulations may fall short of producing reasonable predictions. In this paper, the effect of various loading types on the structural response of round CMP culverts is investigated using 3D finite element (FE) models. The validity of the model was assessed by comparing the model output with previously published results from full-scale laboratory testing. The mechanical behaviour of real soil involves a significant degree of non-linearity. In soil-structure interaction problems such as the one considered here, it seems reasonable to expect that the non-linear behaviour of the soil, together with that of the soil-structure interface, would have a significant effect on the response of the structure. Furthermore, 2D models are limited in their ability to account for certain aspects of the actual, 3D problem. Such aspects include surface live load spreading through the cover soil and the structural behaviour of a corrugated pipe. This paper details the development of a comprehensive, 3D, non-linear FE model capable of simulating the behaviour of intact CMP culverts under backfilling and live loading. The analysis showed that the hyperbolic strain hardening model produced predicted response of the culvert that is very close to the obtained experimental data. However, the numerical results obtained using the Mohr-Coulomb or the linear elastic soil models were of less accuracy.

Purpose Low-field (0.55 T) high-performance cardiovascular magnetic resonance (CMR) is an attractive platform for CMR-guided intervention as device heating is reduced around 7.5-fold compared to 1.5 T. This work determines the feasibility of visualizing cardiac radiofrequency (RF) ablation lesions at low field CMR and explores a novel alternative method for targeted tissue destruction: acetic acid chemoablation. Methods N = 10 swine underwent X-ray fluoroscopy-guided RF ablation (6–7 lesions) and acetic acid chemoablation (2–3 lesions) of the left ventricle. Animals were imaged at 0.55 T with native contrast 3D-navigator gated T1-weighted T1w) CMR for lesion visualization, gated single-shot imaging to determine potential for real-time visualization of lesion formation, and T1 mapping to measure change in T1 in response to ablation. Seven animals were euthanized on ablation day and hearts imaged ex vivo. The remaining animals were imaged again in vivo at 21 days post ablation to observe lesion evolution. Results Chemoablation lesions could be visualized and displayed much higher contrast than necrotic RF ablation lesions with T1w imaging. On the day of ablation, in vivo myocardial T1 dropped by 19 ± 7% in RF ablation lesion cores, and by 40 ± 7% in chemoablation lesion cores (p Conclusion The visualization of coagulation necrosis from cardiac ablation is feasible using low-field high-performance CMR. Chemoablation produced a more pronounced change in lesion T1 than RF ablation, increasing SNR and CNR and thereby making it easier to visualize in both 3D navigator-gated and real-time CMR and more suitable for low-field imaging.

BACKGROUND: Pain after rotator cuff repair is commonly managed with opioid medications; however, these medications are associated with serious adverse effects. Relaxation exercises represent a potential nonpharmacologic method of pain management that can be easily implemented without substantial adverse effects; however, the effects of relaxation exercises have not been studied in a practical, reproducible protocol after arthroscopic rotator cuff repair. QUESTIONS/PURPOSES: (1) Does performing relaxation exercises after arthroscopic rotator cuff repair (ARCR) decrease pain compared with standard pain management medication? (2) Does performing relaxation exercises after ARCR decrease opioid consumption? (3) What proportion of patients who used the relaxation techniques believed they decreased their pain level, and what proportion continued using these techniques at 2 weeks? (4) Does performing relaxation exercises after ARCR affect shoulder function? METHODS: During the study period, 563 patients were eligible for inclusion; however, only 146 were enrolled, randomized, and postoperatively followed (relaxation group: 74, control group: 72); 68% (384 of 563) of patients were not contacted due to patient and research staff availability. Thirty-three patients were unenrolled preoperatively or immediately postoperatively due to change in operative procedure (such as, only debridement) or patient request; no postoperative data were collected from these patients. Follow-up proportions were similar between the relaxation and control groups (relaxation: 80%, control: 81%; p = 0.90). The relaxation group received and reviewed educational materials consisting of a 5-minute video and an educational pamphlet explaining relaxation breathing techniques, while the control group did not receive relaxation education materials. Patients recorded their pain levels and opioid consumption during the 5 days after ARCR. Patients also completed the American Shoulder and Elbow Surgeons shoulder score preoperatively and 2, 6, 13, 18, and 26 weeks postoperatively. Linear mixed models were created to analyze postoperative pain, opioid consumption measured in morphine milligram equivalents (MMEs), and shoulder function outcomes. A per-protocol approach was used to correct for patients who were enrolled but subsequently underwent other procedures. RESULTS: There was no difference in pain scores between the relaxation and control groups during the first 5 days postoperatively. There was no difference in pain scores at 2 weeks postoperatively between the relaxation and control groups (3.3 ± 3 versus 3.5 ± 2, mean difference -0.22 [95% CI -1.06 to 0.62]; p = 0.60). There was no difference in opioid consumption during the first 5 days postoperatively between the relaxation and control groups. The use of relaxation exercises resulted in lower 2-week narcotics consumption in the relaxation group than in the control group (309 ± 241 MMEs versus 442 ± 307 MMEs, mean difference -133 [95% CI -225 to -42]; p < 0.01). Sixty-two percent (41 of 66) of patients in the relaxation group believed the relaxation exercises decreased their pain levels. Fifty-two percent (34 of 66) were still performing the exercises at 2 weeks postoperatively. During the 6-month follow-up period, there was no difference in shoulder function between the relaxation and control groups CONCLUSION: The preoperative administration of quick, basic relaxation exercises allowed patients to use appreciably lower opioid analgesic doses over the first 2 weeks after ARCR, without any worsening of pain scores. We consider this result promising but preliminary; it is possible that a more intense mindfulness intervention—the one we studied here was disseminated using only a 5-minute video—would deliver reductions in pain and further reductions in opioid usage. LEVEL OF EVIDENCE: Level II, therapeutic study.

Inspection agencies have been increasingly implementing unmanned aerial systems (UAS) for bridge inspections. Currently, UAS are typically used for long-range monitoring and surveillance tasks, but bridge managers are hopeful that they may be utilized for detailed inspection, such as condition assessments and the inspection of fracture critical members (FCMs) in the near future. As an assistive tool for visual inspections, the accuracy of UAS-assisted inspections is unknown. This study investigates the relationship between the characteristics of the individual inspectors and a set of performance metrics associated with UAS-assisted FCM inspections. Four bridge inspectors used a UAS to inspect a series of full-sized bridge specimens with known fatigue cracks. The inspection videos were later shared with 19 bridge inspectors for a desk review. The performance of each inspector was evaluated and compared with the results from 30 hands-on inspections of the same specimens. The results showed that an inspector’s past experience with UAS, licensure, and academic degree could have a significant influence on one or more of the three defined performance metrics. The comparison between the results of the UAS-assisted inspections and the hands-on inspections revealed that crack detection was comparable. However, the hands-on inspections were more accurate.

Introduction Resistance training (RT) is the most effective way to increase muscle mass and function in older adults both with/without sarcopenia/frailty. In younger adults, when RT is performed to muscle failure the load lifted does not mediate the magnitude of response, but there are no studies in older adults. We aimed to determine the feasibility of recruitment to a RT intervention working to muscle failure at different loads in frail and healthy older adults. Methods We performed an 8-week randomised feasibility trial of lower limb RT to volitional muscular failure, at high and low load. Participants were recruited via hospital outpatient clinics and newspaper advertisements. Outcomes included: frailty assessment (Fried criteria); muscle strength (maximum voluntary contraction/one-repetition maximum); functional abilities (Short Physical Performance Battery); safety/adverse events were recorded via a log, and patient experiences from focus groups. Results 110 people were assessed for eligibility, and 58 randomised (frail n = 6, prefrail n = 20, robust n = 32) to either high (n = 30) or low load (n = 28) groups. Mean age of participants was 72 years (range 65–93), 36 were female, 22 male. Session attendance was 95% (high load) and 90.4% (low load). Most participants were recruited via advertisements. All participants reported feeling safe and reassured in the RT sessions. Two participants had a serious adverse event, one related to RT (hypotension) and several had adverse events (three intervention-related). Pain was reported at both loads (high n = 9, low n = 8) yet all completed. There were no differences (P > 0.05) in effects of RT outcome variables between low and high load groups. Conclusion In this feasibility trial the recruitment of frail patients via clinics was limited. Performing supervised RT to muscle failure in older adults was safe/acceptable and the load at which RT was performed did not influence its efficacy. Future research into the effectiveness of such RT is warranted.

Highlights • Despite a UK national lockdown, the incidence of open lower limb fractures presenting to our trauma centre was comparative to pre-pandemic levels. • Road traffic accidents continue to be the most common mechanism of injury, possibly related to an increase in speeding. • High energy injuries predominate in males. • Time to initial debridement and definitive wound coverage was not significantly affected. The average length of stay in hospital was reduced., Background: COVID-19 has created huge pressures on healthcare systems. The ongoing provision of major trauma services during this time has proved challenging. We report our experience of managing open lower limb fractures (oLLFs) during the pandemic in a London major trauma centre (MTC). Methods: This was a prospective study of all open lower limb fractures presenting to our unit over the initial 48 days of UK government lockdown - 24th March till 10th May 2020. Results were compared to the same time period in 2019 retrospectively. Epidemiological data, mechanism, Gustilo-Anderson (G-A) severity grading, time to initial debridement and definitive coverage were analysed. Results: There was a 64% reduction in emergency department (ED) attendances (25,264 vs 9042). There was an 18% reduction in oLLFs (22 vs 18). Approximately three-quarters of injuries were in males across both cohorts (77% vs 78%) and tended to occur in younger patients (median age, 37 vs 35). Road-traffic-accidents (RTAs) were the most common injury mechanism in both 2019 and lockdown, but a rise in jumpers from height was seen in the latter. A similar pattern of G-A severities were seen, however only 3 injuries during lockdown required major soft tissue reconstruction. There was no significant difference in times taken for initial debridement (p = 0.72786) or definitive wound coverage (p = 0.16152). A greater proportion of independent operating was seen during lockdown between orthopaedics and plastic surgery. Conclusions: Despite government lockdown measures, oLLFs still placed significant burden on our MTC. Notwithstanding significant staffing alterations and theatre pressures, we have been able to ensure these lower limb emergencies remain a surgical priority and have managed to utilise resources appropriately.

Background Although stool softeners and laxatives are commonly prescribed for postoperative constipation, it is unclear if they are effective during the postoperative period. The data gained from this study will be beneficial for advanced practitioners when examining for postoperative constipation concerns. Purpose This study aimed to investigate the efficacy of docusate sodium and senna glycoside in the prevention and treatment of constipation following rotator cuff repair (RCR). Methods Patients (n = 107) were randomized to receive docusate sodium, senna glycoside, or nothing (control) in addition to a standardized postoperative protocol. Patients maintained a daily bowel-movement log for postoperative days 0-10. Constipation symptoms and quality of life were assessed preoperatively and at 2 and 6 weeks postoperatively using the Patient Assessment of Constipation Symptoms (PAC-SYM) and Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaires. Results Sixty-seven percent of patients experienced constipation. There was no difference in the prevalence of constipation in the docusate, senna, and control groups (71.4%, 66.7%, and 64.3%, respectively; p = .88). Neither PAC-SYM nor PAC-QOL scores significantly differed between the 3 groups at any time point during 6-week follow-up (p > .05). Implications for practice The majority (67%) of patients experience postoperative constipation following RCR. Although docustate sodium and senna glycoside are common first-line agents for the treatment of constipation, they are ineffective during the postoperative period. Providers need to explore other treatment modalities for postoperative constipation pain.

Background Contemporary incidence data for venous thromboembolism (VTE) from racially diverse populations are limited. The racial distribution of Oklahoma County closely mirrors that of the United States. Objective To evaluate VTE incidence and mortality, including demographic and racial subgroups. Design Population-based prospective study. Setting We conducted VTE surveillance at all relevant tertiary care facilities and outpatient clinics in Oklahoma County, Oklahoma during 2012 to 2014, using both active and passive methods. Active surveillance involved reviewing all imaging reports used to diagnose VTE. Passive surveillance entailed identifying VTE events from hospital discharge data and death certificate records. Measurements We used Poisson regression to calculate crude, age-stratified, and age-adjusted incidence and mortality rates per 1,000 population per year and 95% confidence intervals (CIs). Results The incidence rate of all VTE was 3.02 (2.92–3.12) for those age ≥18 years and 0.05 (0.04–0.08) for those Conclusion The age-adjusted VTE incidence and mortality rates vary substantially by race. The incidence of three per 1,000 adults per year indicates an important disease burden, and is informative of the burden in the U.S. population.

Background Tigilanol tiglate (TT) is a novel small molecule for intratumoral treatment of nonmetastatic mast cell tumors (MCTs) in dogs. In a randomized controlled clinical study, 75% of dogs that received a single TT treatment achieved complete resolution of the MCT by 28 days, with no recurrence in 93% of dogs at 84 days. Critical to TT's efficacy was the area of the wound (tissue deficit) after slough of the necrotic tumor relative to pretreatment tumor volume. Objectives To analyze data collected during the previous study to (a) describe wounds after slough of treated MCTs and (b) identify determinants of wound area and speed of wound healing. Methods Wound presence, condition, and area were determined from clinical records of 117 dogs over 84 days after a single intratumoral TT treatment. Results Tumor slough occurred 3 to 14 days after treatment, exposing granulation tissue in the wound bed. Wound area after tumor slough in general was related to pretreatment tumor volume, with maximal recorded wound area fully evident in 89% of dogs by day 7. In dogs achieving complete tumor resolution, all wounds were left to heal by secondary intention. Bandaging and other wound management interventions only were required in 5 dogs. Time to healing (ie, full re-epithelialization of treatment site) depended on wound area and location on the body, with most wounds being fully healed between 28 and 42 days after treatment. Conclusions Wound area and healing after slough of TT-treated tumors follow a consistent clinical pattern for most dogs.

This paper characterizes the effective conductivity of lossy metal materials fabricated with additive manufacturing processes at microwave frequencies using a resonant cavity approach. Specifically addressed is the powder bed fusion additive manufacturing process utilizing AlSi10Mg material at Ku-band. The details of the procedure for converting device parameters that characterize the resonant cavity to material properties are given. Trade-offs between the precision of the conductivity and the quality factor of the cavity are discussed relevant to the design of the cavity. A best-fit matching procedure is made between the measured response of the manufactured cavities and the simulated results. The conductivity with statistical deviation for various fabricated cavities from different vendors is reported. Examples of various designs of fabricated prototype waveguide feed components are presented. The predicted and measured performance of each component is compared, validating the process.

Real-time magnetic resonance imaging (RT-MRI) allows for imaging dynamic processes as they occur, without relying on any repetition or synchronization. This is made possible by modern MRI technology such as fast-switching gradients and parallel imaging. It is compatible with many (but not all) MRI sequences, including spoiled gradient echo, balanced steady-state free precession, and single-shot rapid acquisition with relaxation enhancement. RT-MRI has earned an important role in both diagnostic imaging and image guidance of invasive procedures. Its unique diagnostic value is prominent in areas of the body that undergo substantial and often irregular motion, such as the heart, gastrointestinal system, upper airway vocal tract, and joints. Its value in interventional procedure guidance is prominent for procedures that require multiple forms of soft-tissue contrast, as well as flow information. In this review, we discuss the history of RT-MRI, fundamental tradeoffs, enabling technology, established applications, and current trends. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY STAGE: 1.

Rationale: Infections by Burkholderia species bacteria in CF maybe transmissible, necessitating infection control measures, and remain a serious cause of morbidity and mortality. The last major stu...

Background Tigilanol tiglate (TT) is a novel small molecule approved by the European Medicines Agency for intratumoral treatment of mast cell tumors (MCTs) in dogs. In a randomized controlled clinical efficacy and safety study in the United States, 85 of 116 dogs that received a single TT injection achieved complete response (CR) of the treated MCT by day 28. Objective To evaluate the durability of the TT treatment response achieved at day 28 in the U.S. study by assessing MCT recurrence at the treatment site 6 and 12 months after TT administration. Animals Eighty-five dogs previously treated with TT. Methods Dogs that achieved CR at day 28 were assessed retrospectively for the presence or absence of MCT at the treatment site using records from clinical visits and telephone interviews with owners. Dogs unavailable at an assessment time were considered lost-to-follow-up and data for their last assessment used in the final analysis. Results By 12 months after TT treatment, 64 dogs remained evaluable, with 21 unavailable. Of evaluable patients, 57 (89%) remained tumor free at the treatment site and 7 (11%) had developed recurrence. All recurrences occurred within the first 6 months, predominantly (5/7, 71%) within the first 12 weeks. Conclusions and clinical importance Tigilanol tiglate provided a durable long-term local response for the treatment of MCT in dogs.

Statement of problem Intraoral scanners (IOSs), facial scanners (FSs), and computer-aided design (CAD) software programs have become powerful tools for treatment planning. However, discrepancies in perception regarding 2-dimensional (2D) or 3-dimensional (3D) simulations by dentists, dental students, and laypeople have not been analyzed. Purpose The purpose of this observational study was to analyze the perceptions of laypersons, dental students, and dentists regarding disparities of the maxillary dental midline and the occlusal plane when analyzing the dental discrepancies on 2D- and 3D-clinical simulations. Material and methods A female model was digitized by using an FS, IOS, and a full-face smile photograph. Dental discrepancies were simulated by using a 2D photograph (2D group) and 3D scan (3D group) of the model. In both simulation groups, 2 subgroups were produced. The occlusal plane of the first subgroup was modified in 1-degree increments without changing the dental midline or the position of the maxillary dental incisors. In the second subgroup, the occlusal plane was modified by using the same increments, but the maxillary central incisors and dental midline were altered to match the inclination of the occlusal plane. A total of 300 participants (N=300) were asked to rate the 2D images (N=12) and 3D videos (N=12) on a 1-to-6 scale and answer a questionnaire. Ordinal logistic regression was used to analyze the ratings. Results The ratings decreased with the increased tilt of the occlusal plane, and the layperson group gave consistently higher ratings than the other 2 groups. For dentists, the odds of giving a higher versus lower rating decreased by almost a half for each degree of tilt. However, for students, that effect was diminished by a positive interaction term, and for laypersons, the effect was even less. Students gave similar ratings to dentists, but laypersons gave higher ratings. As the age of the participants increased, however, the ratings also increased. The use of 3D versus 2D images had a positive effect on the ratings, but the effect decreased for the student observers and decreased even further for laypersons. Furthermore, midline alteration led to higher ratings but also resulted in worsening of the odds ratio for the tilt. Seventy percent of the dentists, 57% of the dental students, and 52% of the laypersons preferred 2D simulations to 3D simulations. Conclusions Dentists, dental students, and laypersons decreased their ratings with increased inclination of the occlusal plane; however, laypersons still graded all the 2D and 3D images as esthetically pleasant, giving consistently higher ratings than the dentists and dental students. Overall, 3D simulations obtained higher ratings than 2D images, but the positive effect decreased for the student observers and decreased even further for laypersons.

This article provides a comprehensive overview of hand tendon injuries. It has been tailored towards healthcare professionals who will be the first to assess these injuries and instigate appropriate management. It discusses the essential hand anatomy to be aware of, how to assess tendon injuries, their initial management and also the definitive surgical interventions used, if required. Rehabilitation techniques are also discussed, as this is also key to good functional outcomes. Missed injuries, or delay in their diagnosis and referral to specialist hand surgeons, can cause a large amount of morbidity for patients and therefore it is important that they are picked up in a timely manner.

Background Egg allergy affects almost 1 in 10 Australian infants. Early egg introduction has been associated with a reduced risk in developing egg allergy; however, the immune mechanisms underlying this protection remain unclear. Objective To examine the role of regulatory immune cells in tolerance induction during early egg introduction. Methods Cryopreserved peripheral blood mononuclear cells (PBMC) were obtained from infants from 2 randomized controlled trials of early introduction of egg for the primary prevention of egg allergy; BEAT (at 12 months, n = 42) and STEP (at 5 months n = 82; 12 months n = 82) study cohorts. In vitro ovalbumin-stimulated PBMC were analyzed by flow cytometry for presence of ovalbumin-specific regulatory T cells, using activation markers, FoxP3, and IL-10 expression. Ovalbumin-specific regulatory B cells were identified by co-expression of fluorescence-conjugated ovalbumin and IL-10. Results Specific, age-dependent expansion of ovalbumin-specific regulatory T cells was only observed in infants who (a) had early egg introduction and (b) did not have egg allergy at 12 months. This expansion was blunted or impaired in children who did not undergo early egg introduction and in those with clinical egg allergy at 12 months. Infants with egg allergy at 12 months of age also had reduced frequency of ovalbumin-specific regulatory B cells compared to egg-tolerant infants. Conclusion Early egg introduction and clinical tolerance to egg were associated with expansion of ovalbumin-specific T and B regulatory cells, which may be an important developmental process for tolerance acquisition to food allergens.

Objective The purpose of the study is to compare conventional linear and fingertip ultrasound transducers, for the evaluation of umbilical catheters, with radiography. Fingertip ultrasound transducers have the potential to simplify sonographic examination due to their small size and ability to fit on a finger. Study design A prospective, IRB approved comparative study was performed. Linear and fingertip sonographic images were obtained around the same time as a radiograph in neonates with umbilical catheters by two board certified pediatric radiologists and a radiology resident. The positions of catheters were then compared across all three modalities. Result A total of 41 catheters were evaluated, which included 14 arterial and 27 venous catheters. Two venous catheters were not identified by the linear transducer and one arterial catheter tip was not identified by the fingertip transducer. Conclusion A fingertip ultrasound probe can be used to evaluate umbilical catheter positioning for potentially faster sonographic examination and decrease the need for repeated radiation.

Background The PEPITES (Peanut EPIT Efficacy and Safety) trial, a 12-month randomized controlled study of children with peanut allergy and 4 to 11 years old, previously reported the safety and efficacy of epicutaneous immunotherapy (EPIT) for peanut allergy (250 μg, daily epicutaneous peanut protein; DBV712 250 μg). Objective We sought to assess interim safety and efficacy of an additional 2 years of EPIT from the ongoing (5-year treatment) PEOPLE (PEPITES Open-Label Extension) study. Methods Subjects who completed PEPITES were offered enrollment in PEOPLE. Following an additional 2 years of daily DBV712 250 μg, subjects who had received DBV712 250 μg in PEPITES underwent month-36 double-blind, placebo-controlled food challenge with an optional month-38 sustained unresponsiveness assessment. Results Of 213 eligible subjects who had received DBV712 250 μg in PEPITES, 198 (93%) entered PEOPLE, of whom 141 (71%) had assessable double-blind, placebo-controlled food challenge at month 36. At month 36, 51.8% of subjects (73 of 141) reached an eliciting dose of ≥1000 mg, compared with 40.4% (57 of 141) at month 12; 75.9% (107 of 141) demonstrated increased eliciting dose compared with baseline; and 13.5% (19 of 141) tolerated the full double-blind, placebo-controlled food challenge of 5444 mg. Median cumulative reactive dose increased from 144 to 944 mg. Eighteen subjects underwent an optional sustained unresponsiveness assessment; 14 of those (77.8%) maintained an eliciting dose of ≥1000 mg at month 38. Local patch-site skin reactions were common but decreased over time. There was no treatment-related epinephrine use in years 2 or 3. Compliance was high (96.9%), and withdrawals due to treatment-related adverse events were low (1%). Conclusions These results demonstrate that daily EPIT treatment for peanut allergy beyond 1 year leads to continued response from a well-tolerated, simple-to-use regimen.

Purpose Intraventricular neuroendoscopic techniques, particularly third ventriculostomy, are employed increasingly in the management of infantile hydrocephalus. However, surgical access to the ventricular cavities is associated with a risk of post-operative cerebrospinal fluid (CSF) leak. Here, we describe a structured, multi-layered approach to wound opening and closure which aims to maximise the natural tissue barriers against CSF leakage. We present a series of patients undergoing this technique and subsequently review the literature regarding opening and closure techniques in paediatric intraventricular neuroendoscopic procedures. Methods We performed a retrospective case series analysis of patients under 1 year of age who underwent intraventricular neuroendoscopic procedures in a single institution over a 5-year period. Patients were identified from an institutional operative database, and operation notes and clinical records were subsequently reviewed. Results 28 patients fulfilled the inclusion criteria for this study. The mean age at operation was 9 weeks. 27 patients underwent endoscopic third ventriculostomy whilst 1 underwent endoscopic septostomy, and all patients underwent our structured, multi-layered opening and closure technique. Follow-up ranged from 4 months to 5 years. There were no cases of post-operative CSF leak, infection or wound breakdown. 12 patients remained shunt-free at the last follow-up, with the remaining 16 requiring shunt insertion for progressive hydrocephalus at a mean of 24 days post-operatively. Conclusion Various methods aiming to prevent post-operative CSF leak have been reported in the literature. We propose that our institutional technique may be of benefit in minimising this risk in infants undergoing endoscopic third ventriculostomy and similar intraventricular neuroendoscopic procedures.

PURPOSE: The gradient system transfer function (GSTF) can be used to describe the dynamic gradient system and applied for trajectory correction in non-Cartesian MRI. This study compares the field camera and the phantom-based methods to measure the GSTF and implements a compensation for the difference in measurement dwell time. METHODS: The self-term GSTFs of a MR system were determined with two approaches: 1) using a dynamic field camera and 2) using a spherical phantom-based measurement with standard MR hardware. The phantom-based GSTF was convolved with a box function to compensate for the dwell time dependence of the measurement. The field camera and phantom-based GSTFs were used for trajectory prediction during retrospective image reconstruction of 3D wave-CAIPI phantom images. RESULTS: Differences in the GSTF magnitude response were observed between the two measurement methods. For the wave-CAIPI sequence, this led to deviations in the GSTF predicted trajectories of 4% compared to measured trajectories, and residual distortions in the reconstructed phantom images generated with the phantom-based GSTF. Following dwell-time compensation, deviations in the GSTF magnitudes, GSTF-predicted trajectories, and resulting image artifacts were eliminated (< 0.5% deviation in trajectories). CONCLUSION: With dwell time compensation, both the field camera and the phantom-based GSTF self-terms show negligible deviations and lead to strong artifact reduction when they are used for trajectory correction in image reconstruction.

Objective: 22q11.2 deletion syndrome (22q11DS) is among the strongest known genetic risk factors for schizophrenia. Previous studies have reported variable alterations in subcortical brain structures in 22q11DS. To better characterize subcortical alterations in 22q11DS, including modulating effects of clinical and genetic heterogeneity, the authors studied a large multicenter neuroimaging cohort from the ENIGMA 22q11.2 Deletion Syndrome Working Group. Methods: Subcortical structures were measured using harmonized protocols for gross volume and subcortical shape morphometry in 533 individualswith 22q11DS and 330matched healthy control subjects (age range, 6-56 years; 49% female). Results: Compared with the control group, the 22q11DS group showed lower intracranial volume (ICV) and thalamus, putamen, hippocampus, and amygdala volumes and greater lateral ventricle, caudate, and accumbens volumes (Cohen's d values, 20.90 to 0.93). Shape analysis revealed complex differences in the 22q11DS group across all structures. The larger A-D deletion was associated with more extensive shape alterations compared with the smaller A-B deletion. Participants with 22q11DS with psychosis showed lower ICV and hippocampus, amygdala, and thalamus volumes (Cohen's d values, 20.91 to 0.53) compared with participants with 22q11DS without psychosis. Shape analysis revealed lower thickness and surface area across subregions of these structures. Compared with subcortical findings from other neuropsychiatric disorders studied by the ENIGMA consortium, significant convergence was observed between participants with 22q11DS with psychosis and participants with schizophrenia, bipolar disorder, major depressive disorder, and obsessive-compulsive disorder. Conclusions: In the largest neuroimaging study of 22q11DS to date, the authors found widespread alterations to subcortical brain structures, which were affected by deletion size and psychotic illness. Findings indicate significant overlap between 22q11DS-associated psychosis, idiopathic schizophrenia, and other severe neuropsychiatric illnesses.

Stress causes symptom exacerbation in functional disorders of the urinary bladder. However, the potential mediators and underlying mechanisms of stress effects on micturition reflex function are unknown. We have characterized PACAP (Adcyap1) and PAC1 receptor (Adcyap1r1) signaling in stress-induced urinary bladder dysfunction in mice. We determined PACAP and PAC1 transcripts and protein expressions in the urinary bladder and lumbosacral dorsal root ganglia (DRG) and spinal cord in repeated variate stress (RVS) or control mouse (handling only) groups. RVS in mice significantly (p ≤ 0.01) increased serum corticosterone and urinary bladder NGF content and decreased weight gain. PACAP and PAC1 mRNA and protein were differentially regulated in lower urinary tract tissues with changes observed in lumbosacral DRG and spinal cord but not in urinary bladder. RVS exposure in mice significantly (p ≤ 0.01) increased (2.5-fold) voiding frequency as determined using conscious cystometry. Intrabladder administration of the PAC1 receptor antagonist, PACAP(6-38) (300 nM), significantly (p ≤ 0.01) increased infused volume (1.5-2.7-fold) to elicit a micturition event and increased the intercontraction interval (i.e., decreased voiding frequency) in mice exposed to RVS and in control mice, but changes were smaller in magnitude in control mice. We also evaluated the effect of PAC1 blockade at the level of the urinary bladder on pelvic sensitivity in RVS or control mouse groups using von Frey filament testing. Intrabladder administration of PACAP(6-38) (300 nM) significantly (p ≤ 0.01) reduced pelvic sensitivity following RVS. PACAP/receptor signaling in the CNS and PNS contributes to increased voiding frequency and pelvic sensitivity following RVS and may represent a potential target for therapeutic intervention.

Context Approximately half of individuals who sustain a concussion do not immediately report their injuries. Motivators for not reporting include thinking the suspected concussion was not a serious injury and wanting to continue participating in activity. Additionally, military personnel have concerns about how concussions may affect their careers. However, delayed reporting can prolong neurobehavioral recovery. Understanding the frequency of delayed reporting and contributing factors will aid in identifying individuals who may be more likely to delay reporting. Objective To describe the frequency of delayed concussion reporting by service academy cadets and determine if sex, injury setting, sport level, or medical history is capable of predicting delayed reporting. Design Cohort study. Setting Service academies. Patients or Other Participants A total of 316 patients with concussions were observed from January 2014 to August 2016. Main Outcome Measure(s) All cadets completed an annual concussion baseline collection of demographic, medical history, and sports participation information. Delayed concussion reporting served as the outcome variable. Predictor variables were sex, injury setting, and sport level, as well as concussion, headache, and learning disorder history. Frequencies were calculated to describe the proportion of participants who delayed reporting. Univariable and multivariable logistic regression models were used to assess if the predictor variables were associated with delayed concussion reporting. Odds ratios (ORs) and 95% confidence intervals were calculated for all variables included in the final model. Results Of the patients with concussion, 51% were classified as delayed reporting. In univariable models, females (OR = 1.70) and National Collegiate Athletic Association cadet-athletes (OR = 1.98) were more likely to delay reporting than males and intramural cadet-athletes, respectively. The multivariable model yielded similar findings. Conclusions Roughly half of the cadets who sustained a concussion failed to immediately report their injury. Specifically, our data suggested that female cadets, cadets injured outside of competition, and highly competitive cadet-athletes were almost twice as likely to delay reporting as others.

Context Assessments of the duration of concussion recovery have primarily been limited to sport-related concussions and male contact sports. Furthermore, whereas durations of symptoms and return-to-activity (RTA) protocols encompass total recovery, the trajectory of each duration has not been examined separately. Objective To identify individual (eg, demographics, medical history), initial concussion injury (eg, symptoms), and external (eg, site) factors associated with symptom duration and RTA-protocol duration after concussion. Design Cohort study. Setting Three US military service academies. Patients or Other Participants A total of 10 604 cadets at participating US military service academies enrolled in the study and completed a baseline evaluation and up to 5 postinjury evaluations. A total of 726 cadets (451 men, 275 women) sustained concussions during the study period. Main Outcome Measure(s) Number of days from injury (1) until the participant became asymptomatic and (2) to complete the RTA protocol. Results Varsity athlete cadets took less time than nonvarsity cadets to become asymptomatic (hazard ratio [HR] = 1.75, 95% confidence interval = 1.38, 2.23). Cadets who reported less symptom severity on the Sport Concussion Assessment Tool, third edition (SCAT3), within 48 hours of concussion had 1.45 to 3.77 times shorter symptom-recovery durations than those with more symptom severity. Similar to symptom duration, varsity status was associated with a shorter RTA-protocol duration (HR = 1.74, 95% confidence interval = 1.34, 2.25), and less symptom severity on the SCAT3 was associated with a shorter RTA-protocol duration (HR range = 1.31 to 1.47). The academy that the cadet attended was associated with the RTA-protocol duration (P < .05). Conclusions The initial total number of symptoms reported and varsity athlete status were strongly associated with symptom and RTA-protocol durations. These findings suggested that external (varsity status and academy) and injury (symptom burden) factors influenced the time until RTA.

Objective To describe the disproportionality of racial and ethnic people of color (i.e., minorities) among the student body in schools and colleges of pharmacy (COPs) compared to county-specific United States Census Bureau data. Methods Data were obtained from national databases and published reports from the American Association of Colleges of Pharmacy. In addition, demographic information for enrollees of minority-serving institutions and predominantly white institutions was obtained and racial disproportionality was assessed to determine the degree of concordance between enrollees and the demographics of people within the county that the school was located. Data were evaluated using descriptive statistics. Results Compared to the general population in counties where COPs are located, Asians are over-represented while all other students of color are underrepresented. The top schools that have a negative disproportionality rate for Black students included Thomas Jefferson University (−40.49), Wayne State University (−40.13), Philadelphia College of Pharmacy (−39.90), and the University of Tennessee (−39.74).The top five schools that have a negative disproportionality rate of Hispanic students included Loma Linda University (−45.67), California Health Sciences (−45.64), the University of Southern California (−43.79), the University of the Pacific California (−37.95), and Texas Southern University (−36.65). The enrollments within most COPs do not reflect the racial and ethnic diversity of the counties in which they are located. Conclusions To meet the healthcare needs of an increasingly diverse population, each institution should establish a strategic plan for increasing diversity and evaluating and adopting best practices.

Background The authors conducted a survey of the American Academy of Pediatric Dentistry (AAPD) to determine awareness of the Image Gently Campaign in Dentistry (IGCD) and to ascertain radiologic practices, including radiation dose-reduction strategies such as rectangular collimation. Methods An institutional review board approved an electronic survey sent to 7,087 AAPD members covering practitioner demographic characteristics, radiographic techniques, and dose-reduction practices, including rectangular collimation. Responses were tabulated and analyzed using binomial tests, χ2 tests, and Fisher exact tests. Results A total of 1,124 pediatric dentists or residents in pediatric dentistry responded, (response rate 16%, margin of error ± 2.7%). The largest group (23.8%) graduated after 2010. More than 90% indicated that they followed American Dental Association (ADA)-AAPD radiation exposure guidelines, but only 33.5% were aware of IGCD. Almost all respondents used direct digital systems, storage phosphor plates, or both. Only 22.3% (n = 220) used rectangular collimation. Nonusers indicated that they were unfamiliar with collimation (33.3%) or concerned about potential for increased cone cuts (30.2%), 11.6% of respondents were unaware of any regulatory requirements for inspections of radiographic equipment recurring at regular intervals, and 4.1% of respondents considered use of lead aprons optional. Conclusions Although the pediatric dentists surveyed believe they are in compliance with ADA-AAPD guidelines, most are unaware of IGCD recommendations. Use of digital radiography is almost ubiquitous, but use of rectangular collimation is limited. Practice Implications Dentists treating children should be familiar with ADA-AAPD radiation exposure guidelines and should consider using the dose-reduction strategies recommended by IGCD.

BACKGROUND Patient expectations may affect their satisfaction and functional outcomes after treatment of musculoskeletal injuries. Although there is evidence that patient expectations of ACL reconstruction (ACLR) are inflated, there is limited knowledge about the relationship between physician and patient expectations and patient outcomes after they completely recover from ACLR. Furthermore, it is unclear if specific patient factors influence these expectations. QUESTIONS/PURPOSES (1) Are patient and surgeon expectations of knee function 18 months after ACLR similar? (2) Are patients' and surgeons' expectations of outcomes similar to patients' actual 2-year outcomes? (3) Is there a relationship between preoperative or intraoperative parameters and expectations? (4) Is there a relationship between preoperative or intraoperative parameters and 2-year ACLR outcomes? METHODS One-hundred twenty-nine patients undergoing primary ACLR were prospectively enrolled in this study, with 98 (76%) completing 2-year follow-up. Patients completed the IKDC Subjective Knee Evaluation preoperatively and at 3, 6, 12, and 24 months postoperatively. Patients also completed the same questionnaires preoperatively to evaluate expected knee function 18 months after surgery. Immediately postoperatively, surgeons completed the same questionnaires regarding the expected postoperative outcome at 18 months postoperative. Preoperative and intraoperative data were collected to determine an association between expectations and outcomes. Nonparametric analysis was performed using the Mann-Whitney U test, the paired Wilcoxon signed ranks tests and Spearman's correlations, as applicable. RESULTS There was no difference between patient and surgeon expectations (patient, 94.8 [range 47.4-100] versus surgeon, 94.3 [range 46-100]; p = 0.283), and there was no correlation between higher patient expectations and higher surgeon expectations (r = 0.168, p = 0.078). Patient and surgeon expectations were greater than the actual postoperative outcomes (2-year postoperative: 89.7 [range 32.2 to 100]; p < 0.0001); however, the differences are unlikely to be perceived. There was no correlation between higher 2-year postoperative outcomes and higher patient expectations (r = 0.14, p = 0.186) or higher surgeon expectations (r = 0.019, p = 0.86). Arthroscopic evidence of cartilage damage was independently associated with the worst patient and surgeon expectations. The surgeons themselves were also independently associated with surgeon expectation (p < 0.001). No parameters were associated with postoperative outcomes. CONCLUSIONS There are no clinically significant differences between surgeon expectations, patient expectations, and 2-year actual outcomes. However, there is also no correlation between the patient expectations, surgeon expectations, and actual outcomes. Although expectations are similar to actual outcomes for most patients, surgeons are unable to accurately predict outcomes for specific patients; thus, preventing adequate patient counseling. Surgeons should be cautious when evaluating and counseling patients preoperatively and avoid assuming high expectations. LEVEL OF EVIDENCE Level II, therapeutic study.

Regional and national legislation mandates the disclosure of “priority” allergens when present as an ingredient in foods, but this does not extend to the unintended presence of allergens due to shared production facilities. This has resulted in a proliferation of precautionary allergen (“may contain”) labels (PAL) that are frequently ignored by food-allergic consumers. Attempts have been made to improve allergen risk management to better inform the use of PAL, but a lack of consensus has led to variety of regulatory approaches and nonuniformity in the use of PAL by food businesses. One potential solution would be to establish internationally agreed “reference doses,” below which no PAL would be needed. However, if reference doses are to be used to inform the need for PAL, then it is essential to characterize the hazard associated with these low-level exposures. For peanut, there are now published data relating to over 3000 double-blind, placebo-controlled challenges in allergic individuals, but a similar level of evidence is lacking for other priority allergens. We present the results of a rapid evidence assessment and meta-analysis for the risk of anaphylaxis to a low-level allergen exposure for priority allergens. On the basis of this analysis, we propose that peanut can and should be considered an exemplar allergen for the hazard characterization at a low-level allergen exposure. Resumen: La legislación regional y nacional exige la divulgación de alérgenos "prioritarios" cuando están presentes como ingrediente en los alimentos, pero esto no se extiende a la presencia involuntaria de alérgenos debido a instalaciones de producción compartidas. Esto ha dado lugar a una proliferación de etiquetas de precaución para alérgenos ("pueden contener") (PAL) que los consumidores alérgicos a los alimentos suelen ignorar. Se han hecho intentos para mejorar la gestión del riesgo de alérgenos para informar mejor el uso de PAL, pero la falta de consenso ha llevado a una variedad de enfoques regulatorios y a la falta de uniformidad en el uso de PAL por parte de las empresas alimentarias. Una posible solución sería establecer “dosis de referencia” acordadas internacionalmente, por debajo de las cuales no se necesitaría PAL. Sin embargo, si se van a utilizar dosis de referencia para informar la necesidad de PAL, entonces es esencial caracterizar el peligro asociado con estas exposiciones de bajo nivel. Para el maní, ahora hay datos publicados relacionados con más de 3000 desafíos doble ciego controlados por placebo en individuos alérgicos, pero falta un nivel similar de evidencia para otros alérgenos prioritarios. Presentamos los resultados de una evaluación rápida de la evidencia y un metanálisis del riesgo deanafilaxia a una exposición a alérgenos de bajo nivel para alérgenos prioritarios. Sobre la base de este análisis, proponemos que el cacahuete puede y debe considerarse un alérgeno ejemplar para la caracterización del peligro en una exposición a un alérgeno de bajo nivel. Instituto de Investigación de Tecnología de Alimentos Fil: Turner, Paul J. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Patel, Nandinee. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Ballmer-Weber, Barbara K. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Ballmer-Weber, Barbara K. Clínica de Dermatología y Alergología. Kantonsspital; Suiza. Fil: Baumert, Joe L. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Blom, W. Marty. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Brooke-Taylor, Simon. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Brough, Helen. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Brough, Helen. King's College London. Departamento de Alergia Pediátrica; Reino Unido. Fil: Campbell, Dianne E. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Campbell, Dianne E. Tecnologías DBV. Montrouge; Francia. Fil: Chen, Hongbing. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Chinthrajah, R. Sharon. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Crevel, René W.R. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Dubois, Anthony E.J. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Ebisawa, Motohiro. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Elizur, Arnon. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Elizur, Arnon. Universidad de Tel Aviv. Facultad de Medicina Sackler. Departamento de Pediatría; Israel. Fil: Gerdts, Jennifer D. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Gowland, M. Hazel. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Houben, Geert F. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Hourihane, Jonathan O.B. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Knulst, André C. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: La Vieille, Sébastien. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: López, María Cristina. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Mills, E.N. Clare. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Polenta, Gustavo Alberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Investigación Tecnología de Alimentos; Argentina. Fil: Polenta, Gustavo Alberto. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Purington, Natasha. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Said, María. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Sampson, Hugh A. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Sampson, Hugh A. Escuela de Medicina Icahn. División de Alergia e Inmunología Pediátricasen. Nueva York. Estados Unidos de América. Fil: Schnadt, Sabine. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Södergren, Eva. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Södergren, Eva. ThermoFisher Scientific; Suecia. Fil: Taylor, Stephen L. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Remington, Benjamin C. Imperial College London. Instituto Nacional del Corazón y los Pulmones; Reino Unido. Fil: Remington, Benjamin C. Grupo BV. Consultoría Remington; Holanda.

Transcranial Doppler (TCD) provides visible and audible real-time feedback during carotid stent procedures as otherwise clinically silent small embolic particles reflect microembolic signals (MES) during their egress from the extracranial carotid artery lesion through the middle cerebral artery en route to the ipsilateral hemisphere. During the formative years of carotid stenting, TCD was an important tool for many pioneers in the field as high-risk anatomic carotid access and lesion characteristics were being defined. In addition TCD helped us understand the flow dynamics related to distal and proximal occlusive embolic protection platforms. Also, the disturbing storm of microembolic signals (MES) at different stages during distal filter protection led to optimization of these system designs and procedural technique. One can’t argue the contribution TCD made to the art and science of carotid stenting through amplifying the embolization signal from the devastating clinical event of stroke seen in less than 10% of patients to the silent smaller microembolic signals ubiquitous to every procedure. While the MES data seems to have more of an academic value, the contemporary CAS program should have access to TCD and consider following periprocedural MCA flow patterns during stenting with proximal flow reversal or flow arrest protection systems. In addition TCD provides significant insight into the physiology of reperfusion syndrome, and changes in MCA flow velocities demonstrated in patients at high risk for reperfusion syndrome in the early post-procedure time period may be helpful to direct treatment. The objective of this monograph is to expose the reader to some of the lessons learned from adjuvant transcranial Doppler during carotid stent-supported angioplasty while also providing insight into current clinically relevant applications.

INTRODUCTION Congenital anomalies were the leading cause of infant mortality, responsible for 23 and 21% of deaths in Oklahoma and the USA, respectively, in 2016. We aimed to determine the prevalence by race/ethnicity and spatial distribution of congenital anomalies to identify geographic and racial/ethnic disparities, particularly among American Indian/Alaska Natives (AI/AN). METHODS We evaluated the prevalence of anomalies by type and race/ethnicity among 648,074 live births in Oklahoma from 1997 to 2009. Prevalence proportion ratios (PPRs) and 95% confidence intervals (CIs) were calculated using Poisson regression. We used Moran's I and Getis-Ord Gi* to evaluate spatial clustering for neural tube defects, critical congenital heart defects (CCHDs), and oral clefts among births whose residence geocoded to the ZIP code or finer level. RESULTS Overall prevalence of anomalies among live births was 3.9%. Non-Hispanic (NH) African American (PPR: 0.87, 95% CI: 0.83, 0.91), Asian/Pacific Islander (PPR: 0.70, 95% CI: 0.63, 0.78), and Hispanic (PPR: 0.87, 95% CI: 0.83, 0.91) children had a lower prevalence of anomalies compared to NH whites. The prevalence in NH AI/AN children was similar to NH whites (PPR: 1.01, 95% CI: 0.97, 1.05). However, differences in specific types of anomalies were observed by race/ethnicity. We observed no spatial autocorrelation for CCHD and oral clefts. Neural tube defects demonstrated spatial autocorrelation (p

Transient receptor potential vanilloid family member 4 (TRPV4) transcript and protein expression increased in the urinary bladder and lumbosacral dorsal root ganglia of transgenic mice with chronic urothelial overexpression of nerve growth factor (NGF-OE). We evaluated the functional role of TRPV4 in bladder function with open-outlet cystometry, void spot assays, and natural voiding (Urovoid) assays with the TRPV4 antagonist HC-067047 (1 μM) or vehicle in NGF-OE and littermate wild-type (WT) mice. Blockade of TRPV4 at the level of the urinary bladder significantly ( P ≤ 0.01) increased the intercontraction interval (2.2-fold) and void volume (2.6-fold) and decreased nonvoiding contractions (3.0-fold) in NGF-OE mice, with lesser effects (1.3-fold increase in the intercontraction interval and 1.3-fold increase in the void volume) in WT mice. Similar effects of TRPV4 blockade on bladder function in NGF-OE mice were demonstrated with natural voiding assays. Intravesical administration of HC-067047 (1 µM) significantly ( P ≤ 0.01) reduced pelvic sensitivity in NGF-OE mice but was without effect in littermate WT mice. Blockade of urinary bladder TRPV4 or intravesical infusion of brefeldin A significantly ( P ≤ 0.01) reduced (2-fold) luminal ATP release from the urinary bladder in NGF-OE and littermate WT mice. The results of the present study suggest that TRPV4 contributes to luminal ATP release from the urinary bladder and increased voiding frequency and pelvic sensitivity in NGF-OE mice.

Food protein enterocolitis syndrome (FPIES) is an uncommon—and often under-recognised—type of food allergy, which generally presents in the first year of life, with tendency for remission in early childhood (although adults may also be affected, with increasing reports of adult FPIES appearing in the literature).1 In contrast to most infant food allergies, FPIES is not IgE-mediated and does not present with ‘typical’ IgE symptoms of skin pruritus and or features of anaphylaxis. Rather, it is characterised by onset of profuse vomiting, typically within 1–3 hours after ingestion of the trigger food, often accompanied by pallor, lethargy, hypothermia and diarrhoea. Although fatalities have not been reported, the ensuing hypovolaemia can be dramatic and intensive care admissions for supportive care are not uncommon. However, most episodes respond well to simple intravenous rehydration, and use of ondansetron, with longer term avoidance of trigger food/s. FPIES does not respond to intramuscular epinephrine. FPIES is a clinical diagnosis, recently strengthened in case definition by publication of international consensus criteria.1 However, given the relatively non-specific presenting clinical features, it is often misdiagnosed as gastroenteritis, sepsis …

Objective: One important concept in informatics is data which meets the principles of Findability, Accessibility, Interoperability and Reusability (FAIR). Standards, such as terminologies (findability), assist with important tasks like interoperability, Natural Language Processing (NLP) (accessibility) and decision support (reusability). One terminology, Solor, integrates SNOMED CT, LOINC and RxNorm. We describe Solor, HL7 Analysis Normal Form (ANF), and their use with the high definition natural language processing (HD-NLP) program. Methods: We used HD-NLP to process 694 clinical narratives prior modeled by human experts into Solor and ANF. We compared HD-NLP output to the expert gold standard for 20% of the sample. Each clinical statement was judged “correct” if HD-NLP output matched ANF structure and Solor concepts, or “incorrect” if any ANF structure or Solor concepts were missing or incorrect. Judgements were summed to give totals for “correct” and “incorrect”. Results: 113 (80.7%) correct, 26 (18.6%) incorrect, and 1 error. Inter-rater reliability was 97.5% with Cohen’s kappa of 0.948. Conclusion: The HD-NLP software provides useable complex standards-based representations for important clinical statements designed to drive CDS.

The coronavirus disease 2019 (COVID-19) pandemic has brought attention and awareness to existing health disparities in underrepresented minority communities. Not only were minoritized populations disproportionately and negatively affected by COVID-19, but a history of mistrust and other systemic barriers prevented access to treatment and testing and even affected access and acceptance of the current vaccines. Pharmacists are essential to the provision of care for the general population, particularly during global crises. Minoritized pharmacists play an even greater role as partners with public health officials to translate science and build trust in minoritized community members who are hesitant about vaccine development, safety, and efficacy. Dedicated to representing the views and ideals of minority pharmacists on critical issues affecting health care, the National Pharmaceutical Association (NPhA) has been at the forefront of the pandemic. Throughout the pandemic, NPhA has prioritized the role of underrepresented practitioners, striving to improve awareness and access to underrepresented communities. While delivering education and information about the COVID-19 vaccine, clinical trials, population prioritization, and federal funding to our service areas and target populations, NPhA continues to challenge health care myths and address historical conflicts and systemic racism that often dictate the access to treatment and quality health care.

BACKGROUND: MRI T2* and R2* mapping have gained clinical acceptance for noninvasive assessment of iron overload. Lower field MRI may offer increased measurement dynamic range in patients with high iron concentration and may potentially increase MRI accessibility, but it is compromised by lower signal-to-noise ratio that reduces measurement precision. PURPOSE: To characterize a high-performance 0.55 T MRI system for evaluating patients with liver iron overload. STUDY TYPE: Prospective. POPULATION: Forty patients with known or suspected iron overload (sickle cell anemia [n = 5], β-thalassemia [n = 3], and hereditary spherocytosis [n = 2]) and a liver iron phantom. FIELD STRENGTH/SEQUENCE: A breath-held multiecho gradient echo sequence at 0.55 T and 1.5 T. ASSESSMENT: Patients were imaged with T2*/R2* mapping 0.55 T and 1.5 T within 24 hours, and 16 patients returned for follow-up exams within 6–16 months, resulting in 56 paired studies. Liver T2* and R2* measurements and standard deviations were compared between 0.55 T and 1.5 T and used to validate a predictive model between field strengths. The model was then used to classify iron overload at 0.55 T. STATISTICAL TESTS: Linear regression and Bland–Altman analysis were used for comparisons, and measurement precision was assessed using the coefficient of variation. A P-value < 0.05 was considered statistically significant. RESULTS: R2* was significantly lower at 0.55 T in our cohort (488 ± 449 s(−1) at 1.5 T vs. 178 ± 155 s(−1) at 0.55 T, n = 56 studies) and in the patients with severe iron overload (937 ± 369 s(−1) at 1.5 T vs. 339 ± 127 s(−1) at 0.55 T, n = 23 studies). The coefficient of variation indicated reduced precision at 0.55 T (3.5 ± 2.2% at 1.5 T vs 6.9 ± 3.9% at 0.55 T). The predictive model accurately predicted 1.5 T R2* from 0.55 T R2* (Bland Altman bias = −6.6 ± 20.5%). Using this model, iron overload at 0.55 T was classified as: severe R2* > 185 s(−1), moderate 81 s(−1) < R2* < 185 s(−1), and mild 45 s(−1) < R2* < 91 s(−1). DATA CONCLUSION: We demonstrated that 0.55 T provides T2* and R2* maps that can be used for the assessment of liver iron overload in patients. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2

Objective Maternal asthma often complicates pregnancy and is linked with poorer quality of life. Additionally, individuals with asthma are at an increased risk of depression and anxiety. We examined whether asthma during pregnancy is related to parenting stress in the first year postpartum and if this relationship varies with level of asthma control. Methods This cohort survey-based study included mothers with (n = 157) and without (n = 79) asthma. Mothers with asthma participated in this study following participation in a randomized controlled trial of a novel asthma management strategy during pregnancy. Mothers completed the Parenting Stress Index - Short Form during the first 12 months postpartum. Mothers with asthma also completed the Asthma Control Questionnaire. Results Parenting stress did not differ between mothers with and without asthma. Additionally, for mothers with asthma, there were no differences in levels of parenting stress based on asthma control. Conclusions This study suggests that mothers with asthma are not at an increased risk for excessive parenting stress. However, due to response and sampling bias, levels of parenting stress in asthmatic mothers may be underreported in our sample.

PURPOSE: To develop an isotropic high-resolution stack-of-spirals UTE sequence for pulmonary imaging at 0.55 Tesla by leveraging a combination of robust respiratory-binning, trajectory correction, and concomitant-field corrections. METHODS: A stack-of-spirals golden-angle UTE sequence was used to continuously acquire data for 15.5 minutes. The data was binned to a stable respiratory phase based on superoinferior readout self-navigator signals. Corrections for trajectory errors and concomitant field artifacts, along with image reconstruction with conjugate gradient SENSE, were performed inline within the Gadgetron framework. Finally, data were retrospectively reconstructed to simulate scan times of 5, 8.5, and 12 minutes. Image quality was assessed using signal-to-noise, image sharpness, and qualitative reader scores. The technique was evaluated in healthy volunteers, patients with coronavirus disease 2019 infection, and patients with lung nodules. RESULTS: The technique provided diagnostic quality images with parenchymal lung SNR of 3.18 ± 0.0.60, 4.57 ± 0.87, 5.45 ± 1.02, and 5.89 ± 1.28 for scan times of 5, 8.5, 12, and 15.5 minutes, respectively. The respiratory binning technique resulted in significantly sharper images (p < 0.001) as measured with relative maximum derivative at the diaphragm. Concomitant field corrections visibly improved sharpness of anatomical structures away from iso-center. The image quality was maintained with a slight loss in SNR for simulated scan times down to 8.5 minutes. Inline image reconstruction and artifact correction were achieved in

Aim The COVID-19 pandemic forced huge changes in healthcare delivery in the UK within a matter of weeks. We report our experience of managing burns presenting to a UK Major Trauma Centre during the COVID-19 lockdown period. Method Retrospective patient data was collected on aetiology, severity and management of burns during the first six weeks of the government-enforced lockdown. Data was compared with patients presenting with burns during the same period in 2019 (control) and statistical analysis was performed. Results Fifteen patients were treated during the COVID-19 lockdown and fourteen in the control group. Adults treated during the COVID-19 lockdown had a greater total body surface area (TBSA) (9% vs. 2.9%, p 0.035) and were more likely to suffer full thickness burns (40% vs. 0%). In the COVID-19 group all patients that did not require resuscitation, seven of whom met criteria for referral to burns services, were managed locally by the plastic surgery department with good outcomes. Conclusions Despite the increase in severity of adult burns seen during the COVID-19 lockdown period, local plastic surgery units have been able to adapt their practice and successfully manage more complex burns. This adaptability will be key as we move through the pandemic.

Canine high-grade mast cell tumours (HGMCT) are associated with a poor prognosis, are inherently more invasive, and have higher rates of local recurrence. The primary aim of this retrospective study was to assess the efficacy of intratumoural tigilanol tiglate (TT) as a local treatment option. Eighteen dogs with mast cell tumours (MCT) cytologically diagnosed by veterinary pathologists as either high-grade or suspected high-grade MCT were treated with TT. The TT dose was based on tumour volume (0.5 mg TT/cm3 tumour volume) and delivered intratumourally using a Luer lock syringe and a fanning technique to maximise distribution throughout the tumour mass. Efficacy was assessed on the presence/absence of a complete response (CR) to therapy at days 28 and 84 using response evaluation criteria in solid tumours (RECIST). For dogs not achieving a CR after 28 days, the protocol was repeated with a second intratumoural TT injection. Ten out of 18 dogs (56%) in this study achieved and maintained a CR to at least 84 days after their first or second treatment. Six patients were alive and available for evaluation at 2 years, three of those were recurrence free, and a further three patients were recurrence free following a second treatment cycle. Tigilanol tiglate shows efficacy for local treatment of HGMCT, with higher efficacy noted with a second injection if a CR was not achieved following the first treatment. In the event of treatment site recurrence (TSR), the tumour may be controlled with additional treatment cycles. Tigilanol tiglate provides an alternative local treatment approach to dogs with HGMCT that would either pose an unacceptable anaesthetic risk or the tumour location provides a challenge when attempting surgical excision.