Reliability of the TMS-evoked potential in dorsolateral prefrontal cortex.

We currently lack a reliable method to probe cortical excitability noninvasively from the human dorsolateral prefrontal cortex (dlPFC). We recently found that the strength of early and local dlPFC transcranial magnetic stimulation (TMS)-evoked potentials (EL-TEPs) varied widely across dlPFC subregions. Despite these differences in response amplitude, reliability at each target is unknown. Here we quantified within-session reliability of dlPFC EL-TEPs after TMS to six left dlPFC subregions in 15 healthy subjects. We evaluated reliability (concordance correlation coefficient [CCC]) across targets, time windows, quantification methods, regions of interest, sensor- vs. source-space, and number of trials. On average, the medial target was most reliable (CCC = 0.78) and the most anterior target was least reliable (CCC = 0.24). However, all targets except the most anterior were reliable (CCC > 0.7) using at least one combination of the analytical parameters tested. Longer (20 to 60 ms) and later (30 to 60 ms) windows increased reliability compared to earlier and shorter windows. Reliable EL-TEPs (CCC up to 0.86) were observed using only 25 TMS trials at a medial dlPFC target. Overall, medial dlPFC targeting, wider windows, and peak-to-peak quantification improved reliability. With careful selection of target and analytic parameters, highly reliable EL-TEPs can be extracted from the dlPFC after only a small number of trials.

Incidence and Predictors of Breakthrough and Severe Breakthrough Infections of SARS-CoV-2 After Primary Series Vaccination in Adults: A Population-Based Survey of 22 575 Participants.

BACKGROUND: Breakthrough infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are well documented. The current study estimates breakthrough incidence across pandemic waves, and evaluates predictors of breakthrough and severe breakthrough infections (defined as those requiring hospitalization). METHODS: In total, 89 762 participants underwent longitudinal antibody surveillance. Incidence rates were calculated using total person-days contributed. Bias-corrected and age-adjusted logistic regression determined multivariable predictors of breakthrough and severe breakthrough infection, respectively. RESULTS: The incidence was 0.45 (95% confidence interval [CI], .38-.50) during pre-Delta, 2.80 (95% CI, 2.25-3.14) during Delta, and 11.2 (95% CI, 8.80-12.95) during Omicron, per 10 000 person-days. Factors associated with elevated odds of breakthrough included Hispanic ethnicity (vs non-Hispanic white, OR = 1.243; 95% CI, 1.073-1.441), larger household size (OR = 1.251 [95% CI, 1.048-1.494] for 3-5 vs 1 and OR = 1.726 [95% CI, 1.317-2.262] for more than 5 vs 1 person), rural versus urban living (OR = 1.383; 95% CI, 1.122-1.704), receiving Pfizer or Johnson & Johnson versus Moderna, and multiple comorbidities. Of the 1700 breakthrough infections, 1665 reported on severity; 112 (6.73%) were severe. Higher body mass index, Hispanic ethnicity, vaccine type, asthma, and hypertension predicted severe breakthroughs. CONCLUSIONS: Breakthrough infection was 4-25 times more common during the Omicron-dominant wave versus earlier waves. Higher burden of severe breakthrough infections was identified in subgroups.

Antibody Duration After Infection From SARS-CoV-2 in the Texas Coronavirus Antibody Response Survey.

Understanding the duration of antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that causes COVID-19 is important to controlling the current pandemic. Participants from the Texas Coronavirus Antibody Response Survey (Texas CARES) with at least 1 nucleocapsid protein antibody test were selected for a longitudinal analysis of antibody duration. A linear mixed model was fit to data from participants (n = 4553) with 1 to 3 antibody tests over 11 months (1 October 2020 to 16 September 2021), and models fit showed that expected antibody response after COVID-19 infection robustly increases for 100 days postinfection, and predicts individuals may remain antibody positive from natural infection beyond 500 days depending on age, body mass index, smoking or vaping use, and disease severity (hospitalized or not; symptomatic or not).

Long-term immune response to SARS-CoV-2 infection and vaccination in children and adolescents.

BACKGROUND: This analysis examined the durability of antibodies present after SARS-CoV-2 infection and vaccination in children and adolescents. METHODS: Data were collected over 4 time points between October 2020-November 2022 as part of a prospective population-based cohort aged 5-to-19 years (N = 810). Results of the (1) Roche Elecsys® Anti-SARS-CoV-2 Immunoassay for detection of antibodies to the SARS-CoV-2 nucleocapsid protein (Roche N-test); and (2) qualitative and semi-quantitative detection of antibodies to the SARS CoV-2 spike protein receptor binding domain (Roche S-test); and (3) self-reported antigen/PCR COVID-19 test results, vaccination and symptom status were analyzed. RESULTS: N antibody levels reached a median of 84.10 U/ml (IQR: 20.2, 157.7) cutoff index (COI) ~ 6 months post-infection and increased slightly to a median of 85.25 (IQR: 28.0, 143.0) COI at 12 months post-infection. Peak S antibody levels were reached at a median of 2500 U/mL ~6 months post-vaccination and remained for ~12 months (mean 11.6 months, SD 1.20). CONCLUSIONS: This analysis provides evidence of robust durability of nucleocapsid and spike antibodies in a large pediatric sample up to 12 months post-infection/vaccination. This information can inform pediatric SARS-CoV-2 vaccination schedules. IMPACT: This study provided evidence of robust durability of both nucleocapsid and spike antibodies in a large pediatric sample up to 12 months after infection. Little is known about the long-term durability of natural and vaccine-induced SARS-CoV-2 antibodies in the pediatric population. Here, we determined the durability of anti-SARS-CoV-2 spike (S-test) and nucleocapsid protein (N-test) in children/adolescents after SARS-CoV-2 infection and/or vaccination lasts at least up to 12 months. This information can inform future SARS-CoV-2 vaccination schedules in this age group.

Auditory, tactile, and multimodal noise reduce balance variability.

Auditory and somatosensory white noise can stabilize standing balance. However, the differential effects of auditory and tactile noise stimulation on balance are unknown. Prior work on unimodal noise stimulation showed gains in balance with white noise through the auditory and tactile modalities separately. The current study aims to examine whether multimodal noise elicits similar responses to unimodal noise. We recorded the postural sway of healthy young adults who were presented with continuous white noise through the auditory or tactile modalities and through a combination of both (multimodal condition) using a wearable device. Our results replicate previous work that showed that auditory or tactile noise reduces sway variability with and without vision. Additionally, we show that multimodal noise also reduces the variability of sway. Analysis of different frequency bands of sway is typically used to separate open-loop exploratory (< 0.3 Hz) and feedback-driven (> 0.3 Hz) sway. We performed this analysis and showed that unimodal and multimodal white noise affected postural sway variability similarly in both timescales. These results support that the sensory noise effects on balance are robust across unimodal and multimodal conditions and can affect both mechanisms of sway represented in the frequency spectrum. In future work, the parameters of acoustic/tactile manipulation should be optimized for the most effective balance stabilization, and multimodal therapies should be explored for older adults with typical age-related balance instabilities.

Cortical mu rhythms during action and passive music listening.

Brain systems supporting body movement are active during music listening in the absence of overt movement. This covert motor activity is not well understood, but some theories propose a role in auditory timing prediction facilitated by motor simulation. One question is how music-related covert motor activity relates to motor activity during overt movement. We address this question using scalp electroencephalogram by measuring mu rhythms-cortical field phenomena associated with the somatomotor system that appear over sensorimotor cortex. Lateralized mu enhancement over hand sensorimotor cortex during/just before foot movement in foot versus hand movement paradigms is thought to reflect hand movement inhibition during current/prospective movement of another effector. Behavior of mu during music listening with movement suppressed has yet to be determined. We recorded 32-channel EEG (n = 17) during silence without movement, overt movement (foot/hand), and music listening without movement. Using an independent component analysis-based source equivalent dipole clustering technique, we identified three mu-related clusters, localized to left primary motor and right and midline premotor cortices. Right foot tapping was accompanied by mu enhancement in the left lateral source cluster, replicating previous work. Music listening was accompanied by similar mu enhancement in the left, as well as midline, clusters. We are the first, to our knowledge, to report, and also to source-resolve, music-related mu modulation in the absence of overt movements. Covert music-related motor activity has been shown to play a role in beat perception (Ross JM, Iversen JR, Balasubramaniam R. Neurocase 22: 558-565, 2016). Our current results show enhancement in somatotopically organized mu, supporting overt motor inhibition during beat perception.NEW & NOTEWORTHY We are the first to report music-related mu enhancement in the absence of overt movements and the first to source-resolve mu activity during music listening. We suggest that music-related mu modulation reflects overt motor inhibition during passive music listening. This work is relevant for the development of theories relating to the involvement of covert motor system activity for predictive beat perception.

Experimental suppression of transcranial magnetic stimulation-electroencephalography sensory potentials.

The sensory experience of transcranial magnetic stimulation (TMS) evokes cortical responses measured in electroencephalography (EEG) that confound interpretation of TMS-evoked potentials (TEPs). Methods for sensory masking have been proposed to minimize sensory contributions to the TEP, but the most effective combination for suprathreshold TMS to dorsolateral prefrontal cortex (dlPFC) is unknown. We applied sensory suppression techniques and quantified electrophysiology and perception from suprathreshold dlPFC TMS to identify the best combination to minimize the sensory TEP. In 21 healthy adults, we applied single pulse TMS at 120% resting motor threshold (rMT) to the left dlPFC and compared EEG vertex N100-P200 and perception. Conditions included three protocols: No masking (no auditory masking, no foam, and jittered interstimulus interval [ISI]), Standard masking (auditory noise, foam, and jittered ISI), and our ATTENUATE protocol (auditory noise, foam, over-the-ear protection, and unjittered ISI). ATTENUATE reduced vertex N100-P200 by 56%, "click" loudness perception by 50%, and scalp sensation by 36%. We show that sensory prediction, induced with predictable ISI, has a suppressive effect on vertex N100-P200, and that combining standard suppression protocols with sensory prediction provides the best N100-P200 suppression. ATTENUATE was more effective than Standard masking, which only reduced vertex N100-P200 by 22%, loudness by 27%, and scalp sensation by 24%. We introduce a sensory suppression protocol superior to Standard masking and demonstrate that using an unjittered ISI can contribute to minimizing sensory confounds. ATTENUATE provides superior sensory suppression to increase TEP signal-to-noise and contributes to a growing understanding of TMS-EEG sensory neuroscience.

Modality-specific frequency band activity during neural entrainment to auditory and visual rhythms.

Rhythm perception depends on the ability to predict the onset of rhythmic events. Previous studies indicate beta band modulation is involved in predicting the onset of auditory rhythmic events (Fujioka et al., 2009, 2012; Snyder & Large, 2005). We sought to determine if similar processes are recruited for prediction of visual rhythms by investigating whether beta band activity plays a role in a modality-dependent manner for rhythm perception. We looked at electroencephalography time-frequency neural correlates of prediction using an omission paradigm with auditory and visual rhythms. By using omissions, we can separate out predictive timing activity from stimulus-driven activity. We hypothesized that there would be modality-independent markers of rhythm prediction in induced beta band oscillatory activity, and our results support this hypothesis. We find induced and evoked predictive timing in both auditory and visual modalities. Additionally, we performed an exploratory-independent components-based spatial clustering analysis, and describe all resulting clusters. This analysis reveals that there may be overlapping networks of predictive beta activity based on common activation in the parietal and right frontal regions, auditory-specific predictive beta in bilateral sensorimotor regions, and visually specific predictive beta in midline central, and bilateral temporal/parietal regions. This analysis also shows evoked predictive beta activity in the left sensorimotor region specific to auditory rhythms and implicates modality-dependent networks for auditory and visual rhythm perception.

Rationale and development of a manualised dietetic intervention for adults undergoing psychological treatment for an eating disorder.

PURPOSE: Due to the current dearth of literature regarding dietetic treatment for patients with an eating disorder (ED), no manualised dietetic interventions exist to enable the testing of dietetic treatments in this population. This paper aims to: (1) describe the rationale and development of a manualised dietetic intervention for adults undergoing concurrent psychological treatment for an ED; and (2) provide an overview of the feasibility testing of this intervention. METHODS: Current best evidence to date for dietetic treatment in EDs was utilised to develop a manualised dietetic intervention for feasibility testing alongside outpatient psychological 'treatment as usual'. RESULTS: The developed intervention consists of five, dietitian-delivered outpatient sessions: (1) getting started; (2) mechanical eating and dietary rules; (3) estimating portion sizes and social eating; (4) maximising your meal plan and meal preparation; and (5) review and treatment planning as well as pre- and post-intervention assessments. CONCLUSION: This paper is intended as a resource for clinicians and researchers in the conduct of future studies examining dietetic treatment for patients with an ED. LEVEL OF EVIDENCE: Level V, description of a new manualised, reproducible dietetic intervention.

Novel antimicrobial peptide discovery using machine learning and biophysical selection of minimal bacteriocin domains.

Bacteriocins, the ribosomally produced antimicrobial peptides of bacteria, represent an untapped source of promising antibiotic alternatives. However, bacteriocins display diverse mechanisms of action, a narrow spectrum of activity, and inherent challenges in natural product isolation making in vitro verification of putative bacteriocins difficult. A subset of bacteriocins exert their antimicrobial effects through favorable biophysical interactions with the bacterial membrane mediated by the charge, hydrophobicity, and conformation of the peptide. We have developed a pipeline for bacteriocin-derived compound design and testing that combines sequence-free prediction of bacteriocins using machine learning and a simple biophysical trait filter to generate 20 amino acid peptides that can be synthesized and evaluated for activity. We generated 28,895 total 20-mer candidate peptides and scored them for charge, α-helicity, and hydrophobic moment. Of those, we selected 16 sequences for synthesis and evaluated their antimicrobial, cytotoxicity, and hemolytic activities. Peptides with the overall highest scores for our biophysical parameters exhibited significant antimicrobial activity against Escherichia coli and Pseudomonas aeruginosa. Our combined method incorporates machine learning and biophysical-based minimal region determination to create an original approach to swiftly discover bacteriocin candidates amenable to rapid synthesis and evaluation for therapeutic use.

The Role of Posterior Parietal Cortex in Beat-based Timing Perception: A Continuous Theta Burst Stimulation Study.

There is growing interest in how the brain's motor systems contribute to the perception of musical rhythms. The Action Simulation for Auditory Prediction hypothesis proposes that the dorsal auditory stream is involved in bidirectional interchange between auditory perception and beat-based prediction in motor planning structures via parietal cortex [Patel, A. D., & Iversen, J. R. The evolutionary neuroscience of musical beat perception: The Action Simulation for Auditory Prediction (ASAP) hypothesis. Frontiers in Systems Neuroscience, 8, 57, 2014]. We used a TMS protocol, continuous theta burst stimulation (cTBS), that is known to down-regulate cortical activity for up to 60 min following stimulation to test for causal contributions to beat-based timing perception. cTBS target areas included the left posterior parietal cortex (lPPC), which is part of the dorsal auditory stream, and the left SMA (lSMA). We hypothesized that down-regulating lPPC would interfere with accurate beat-based perception by disrupting the dorsal auditory stream. We hypothesized that we would induce no interference to absolute timing ability. We predicted that down-regulating lSMA, which is not part of the dorsal auditory stream but has been implicated in internally timed movements, would also interfere with accurate beat-based timing perception. We show ( n = 25) that cTBS down-regulation of lPPC does interfere with beat-based timing ability, but only the ability to detect shifts in beat phase, not changes in tempo. Down-regulation of lSMA, in contrast, did not interfere with beat-based timing. As expected, absolute interval timing ability was not impacted by the down-regulation of lPPC or lSMA. These results support that the dorsal auditory stream plays an essential role in accurate phase perception in beat-based timing. We find no evidence of an essential role of parietal cortex or SMA in interval timing.

Factors associated with professional identity, job satisfaction and burnout for occupational therapists working in eating disorders: A mixed methods study.

BACKGROUND: Occupational therapists employed within eating disorder services provide unique and valuable interventions. However, existing literature suggests that occupational therapists in this area may be at substantial risk of experiencing poor work-related wellbeing (e.g., high levels of burnout and low levels of job satisfaction). Despite these risks, no previous studies have explored the work-related experiences of occupational therapists in this specialist area of practice. OBJECTIVES: To explore challenges faced by occupational therapists working in eating disorders, their sense of professional identity, burnout and job satisfaction. METHOD: A mixed methods sequential design was adopted. Australian occupational therapists working in eating disorder services were invited to complete a survey exploring job challenges, burnout, professional identity and job satisfaction. Follow-up interviews were conducted and analysed using Braun and Clarke's method of thematic analysis. RESULTS: Ten occupational therapists (representing approximately 50% of the workforce in this specialist area in Australia) participated. There were strong correlations between challenges from the client group and exhaustion (a component of burnout), and moderate correlations between stronger professional identity, pressure to adopt generalist approaches and exhaustion. Qualitative analysis suggested job challenges arose from structural, personal and client-related sources, especially underutilisation of occupational therapy and pressure to adopt non-occupation-based practices. Participants reported using strategies such as maintaining an occupation focus, supervision, professional interactions and maintaining work-life balance to mitigate job stress. CONCLUSION: Occupational therapists working in eating disorders do face challenges. These are particularly related to the lack of evidence base for occupational therapy in this area. Future research should focus on developing further evidence for occupational therapy in eating disorders and designing outcome measures that capture improvements in daily functioning. These efforts would strengthen the role of occupational therapy and may reduce the risk of burnout and improve job satisfaction and sense of professional identity.

Exploring the perceived usefulness of practical food groups in day treatment for individuals with eating disorders.

BACKGROUND/AIM: Recovery from eating disorders is a challenging process. Emerging literature suggests that occupational therapists may provide a useful contribution in delivering purposeful eating-related interventions as a potential treatment to support sustained cognitive and behavioural changes for individuals with eating disorders. This study aimed to evaluate participants' perceptions of the contribution of occupational therapy practical food groups (food based outings and cooking groups) in supporting their functional recovery. METHODS: Individuals attended practical food groups as part of standard treatment at an outpatient eating disorders day program. Ninety-nine participants completed questionnaires at discharge and up to three follow-up points (6, 12 and 24 months). Questions related to practical food groups were analysed, exploring participants' experiences and perceived usefulness of groups using rating-scale and open-ended questions. Open-ended responses were analysed using thematic analysis. Descriptive statistics were calculated for responses to rating-scale questions. RESULTS: At discharge, participants rated the importance and usefulness of practical food groups as high (4.73 and 4.43 on 5-point scales, respectively), but tended to rate their enjoyment of the groups lower (3.50 on a 5-point scale). Some skill transfer was typically reported by participants at discharge (3.92 on a 5-point scale). One core theme, 'success through participation', emerged from qualitative comments. Six subthemes were also identified: helpful components of practical food groups; perceived benefit of exposure; impact of applying cognitive and behavioural skills; challenges affecting participation; facilitating adaptation; and influence of eating disorders on challenging feared foods. CONCLUSION: This study highlights that participation in practical food groups was perceived as useful in assisting individuals to improve eating behaviours and, in some circumstances, transfer these skills into their lives outside of day program. Results suggest that occupational therapists may have an important contribution in delivering these interventions to support recovery and facilitate application of adaptive coping strategies.

Dual Modulation of Nociception and Cardiovascular Reflexes during Peripheral Ischemia through P2Y1 Receptor-Dependent Sensitization of Muscle Afferents.

Numerous musculoskeletal pain disorders are based in dysfunction of peripheral perfusion and are often comorbid with altered cardiovascular responses to muscle contraction/exercise. We have recently found in mice that 24 h peripheral ischemia induced by a surgical occlusion of the brachial artery (BAO) induces increased paw-guarding behaviors, mechanical hypersensitivity, and decreased grip strength. These behavioral changes corresponded to increased heat sensitivity as well as an increase in the numbers of chemosensitive group III/IV muscle afferents as assessed by an ex vivo forepaw muscles/median and ulnar nerves/dorsal root ganglion (DRG)/spinal cord (SC) recording preparation. Behaviors also corresponded to specific upregulation of the ADP-responsive P2Y1 receptor in the DRGs. Since group III/IV muscle afferents have separately been associated with regulating muscle nociception and exercise pressor reflexes (EPRs), and P2Y1 has been linked to heat responsiveness and phenotypic switching in cutaneous afferents, we sought to determine whether upregulation of P2Y1 was responsible for the observed alterations in muscle afferent function, leading to modulation of muscle pain-related behaviors and EPRs after BAO. Using an afferent-specific siRNA knockdown strategy, we found that inhibition of P2Y1 during BAO not only prevented the increased mean blood pressure after forced exercise, but also significantly reduced alterations in pain-related behaviors. Selective P2Y1 knockdown also prevented the increased firing to heat stimuli and the BAO-induced phenotypic switch in chemosensitive muscle afferents, potentially through regulating membrane expression of acid sensing ion channel 3. These results suggest that enhanced P2Y1 in muscle afferents during ischemic-like conditions may dually regulate muscle nociception and cardiovascular reflexes. SIGNIFICANCE STATEMENT: Our current results suggest that P2Y1 modulates heat responsiveness and chemosensation in muscle afferents to play a key role in the development of pain-related behaviors during ischemia. At the same time, under these pathological conditions, the changes in muscle sensory neurons appear to modulate an increase in mean systemic blood pressure after exercise. This is the first report of the potential peripheral mechanisms by which group III/IV muscle afferents can dually regulate muscle nociception and the exercise pressor reflex. These data provide evidence related to the potential underlying reasons for the comorbidity of muscle pain and altered sympathetic reflexes in disease states that are based in problems with peripheral perfusion and may indicate a potential target for therapeutic intervention.

Muscle IL1ß Drives Ischemic Myalgia via ASIC3-Mediated Sensory Neuron Sensitization.

UNLABELLED: Musculoskeletal pain is a significantly common clinical complaint. Although it is known that muscles are quite sensitive to alterations in blood flow/oxygenation and a number of muscle pain disorders are based in problems of peripheral perfusion, the mechanisms by which ischemic-like conditions generate myalgia remain unclear. We found, using a multidisciplinary experimental approach, that ischemia and reperfusion injury (I/R) in male Swiss Webster mice altered ongoing and evoked pain-related behaviors in addition to activity levels through enhanced muscle interleukin-1 beta (IL1ß)/IL1 receptor signaling to group III/IV muscle afferents. Peripheral sensitization depended on acid-sensing ion channels (ASICs) because treatment of sensory afferents in vitro with IL1ß-upregulated ASIC3 in single cells, and nerve-specific knock-down of ASIC3 recapitulated the results of inhibiting the enhanced IL1ß/IL1r1 signaling after I/R, which was also found to regulate afferent sensitization and pain-related behaviors. This suggests that targeting muscle IL1ß signaling may be a potential analgesic therapy for ischemic myalgia. SIGNIFICANCE STATEMENT: Here, we have described a novel pathway whereby increased inflammation within the muscle tissue during ischemia/reperfusion injury sensitizes group III and IV muscle afferents via upregulation of acid-sensing ion channel 3 (ASIC3), leading not only to alterations in mechanical and chemical responsiveness in individual afferents, but also to pain-related behavioral changes. Furthermore, these I/R-induced changes can be prevented using an afferent-specific siRNA knock-down strategy targeting either ASIC3 or the upstream mediator of its expression, interleukin 1 receptor 1. Therefore, this knowledge may contribute to the development of alternative therapeutics for muscle pain and may be especially relevant to pain caused by issues of peripheral circulation, which is commonly observed in disorders such as complex regional pain syndrome, sickle cell anemia, or fibromyalgia.

Efficacy of a 4-Food Elimination Diet for Children With Eosinophilic Esophagitis.

BACKGROUND & AIMS: A 6-food elimination diet induces remission in most children and adults with eosinophilic esophagitis (EoE). The effectiveness of empiric elimination of only 4 foods has not been studied in children. We performed a prospective observational outcome study in children with EoE treated with dietary exclusion of cow's milk, wheat, egg, and soy. The objective was to assess the clinical, endoscopic, and histologic efficacy of this treatment in EoE. METHODS: We recruited children (1-18 years old, diagnosed per consensus guidelines) from 4 medical centers. Study participants (n = 78) were given a proton pump inhibitor twice daily and underwent a baseline esophagogastroduodenoscopy. Subjects were instructed on dietary exclusion of cow's milk, wheat, egg, and soy. Clinical, endoscopic, and histologic assessments were made after 8 weeks. Responders had single foods reintroduced for 8 weeks, with repeat endoscopy to assess for recurrence of active disease. The primary endpoint was histologic remission (fewer than 15 eosinophils per high-powered field). Secondary endpoints included symptom and endoscopic improvements and identification of foods associated with active histologic disease. RESULTS: After 8 weeks on 4-food elimination diet, 50 subjects were in histologic remission (64%). The subjects' mean baseline clinical symptoms score was 4.5, which decreased to 2.3 after 8 weeks of 4-food elimination diet (P < .001). The mean endoscopic baseline score was 2.1, which decreased to 1.3 (P < .001). After food reintroduction, the most common food triggers that induced histologic inflammation were cow's milk (85%), egg (35%), wheat (33%), and soy (19%). One food trigger that induced recurrence of esophageal inflammation was identified in 62% of patients and cow's milk-induced EoE was present in 88% of these patients. CONCLUSIONS: In a prospective study of children with EoE, 8 weeks of 4-food elimination diet induced clinical, endoscopic, and histologic remission in more than 60% of children with EoE. Although less restrictive than 6-food elimination diet, 4-food elimination diet was nearly as effective, and can be recommended as a treatment for children with EoE.

The psychosocial effects of the Li-Fraumeni Education and Early Detection (LEAD) program on individuals with Li-Fraumeni syndrome.

PURPOSE: In the past 5 years, new screening protocols have been developed that provide improved cancer screening options for individuals with Li-Fraumeni syndrome (LFS). Very little has been published on the psychosocial impact of these screening protocols. The goals of this study were to determine how participation in screening impacts individuals psychosocially, to examine the benefits and drawbacks of screening, and to evaluate possible barriers to continued screening. METHODS: We performed a qualitative study consisting of semistructured phone interviews conducted from December 2015 to February 2016 with 20 individuals attending the LFS screening program at MD Anderson Cancer Center. RESULTS: Data analysis showed that benefits of screening include early detection, peace of mind, centralized screening, knowledge providing power, and screening making LFS seem more livable. Perceived drawbacks included logistical issues, difficulty navigating the system, screening being draining, and significant negative emotional reactions such as anxiety, fear, and skepticism. Regardless of the emotions that were present, 100% of participants planned on continuing screening in the program. CONCLUSION: Our data indicate that the perceived benefits of screening outweigh the drawbacks of screening. Individuals in this screening program appeared to have improved psychosocial well-being because of their access to the screening program.Genet Med advance online publication 16 March 2017.

Motor simulation theories of musical beat perception.

There is growing interest in whether the motor system plays an essential role in rhythm perception. The motor system is active during the perception of rhythms, but is such motor activity merely a sign of unexecuted motor planning, or does it play a causal role in shaping the perception of rhythm? We present evidence for a causal role of motor planning and simulation, and review theories of internal simulation for beat-based timing prediction. Brain stimulation studies have the potential to conclusively test if the motor system plays a causal role in beat perception and ground theories to their neural underpinnings.

Internet Cognitive Behavioral Therapy for Women With Postnatal Depression: A Randomized Controlled Trial of MumMoodBooster.

BACKGROUND: There are few published controlled trials examining the efficacy of Internet-based treatment for postnatal depression (PND) and none that assess diagnostic status (clinical remission) as the primary outcome. This is despite the need to improve treatment uptake and accessibility because fewer than 50% of postnatally depressed women seek help, even when identified as depressed. OBJECTIVE: In a randomized controlled trial (RCT), we aimed to test the efficacy of a 6-session Internet intervention (the MumMoodBooster program, previously evaluated in a feasibility trial) in a sample of postnatal women with a clinical diagnosis of depression. The MumMoodBooster program is a cognitive behavioral therapy (CBT) intervention, is highly interactive, includes a partner website, and was supported by low-intensity telephone coaching. METHODS: This was a parallel 2-group RCT (N=43) comparing the Internet CBT treatment (n=21) to treatment as usual (n=22). At baseline and at 12 weeks after enrollment, women's diagnostic status was assessed by telephone with the Standardized Clinical Interview for DSM-IV (SCID-IV) and symptom severity with the Beck Depression Inventory (BDI-II). Depression symptoms were measured repeatedly throughout the study period with the Patient Health Questionnaire (PHQ-9). RESULTS: At the end of the study, 79% (15/19) of women who received the Internet CBT treatment no longer met diagnostic criteria for depression on the SCID-IV (these outcome data were missing for 2 intervention participants). This contrasted with only 18% (4/22) remission in the treatment as usual condition. Depression scores on the BDI-II showed a large effect favoring the intervention group (d=.83, 95% CI 0.20-1.45). Small to medium effects were found on the PHQ-9 and on measures of anxiety and stress. Adherence to the program was very good with 86% (18/21) of users completing all sessions; satisfaction with the program was rated 3.1 out of 4 on average. CONCLUSIONS: Our results suggest that our Internet CBT program, MumMoodBooster, is an effective treatment option for women clinically diagnosed with PND. This is one of only two controlled evaluations of specialized online psychological treatment among women clinically diagnosed with PND. MumMoodBooster appears to be a feasible, effective treatment option, which is potentially accessible to large numbers of women in metropolitan, rural, and remote areas. Future work might be focused profitably on establishing comparability with face-to-face treatments and purely self-guided delivery. We have commenced a larger RCT comparing MumMoodBooster with face-to-face CBT. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ANZCTR): ACTRN12613000113752; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363561 (Archived by WebCite® at http://www.webcitation.org/6f64kuyLf).

Role of coordinators in national and international major trauma services.

Major trauma services in the UK underwent reform in April 2012, following reports that trauma care in England was 'unacceptable' and in need of desperate change, and urgent recommendations were made to improve coordination, costs, and information about trauma care to avoid unnecessary deaths. Following the reconfiguration of services, NHS England highlighted the need for nurse key-workers, or coordinators, to support patients through the major trauma pathway and into rehabilitation. This article examines the literature on the coordinator role to understand its function in UK and international major trauma networks.