Network effects of Stanford Neuromodulation Therapy (SNT) in treatment-resistant major depressive disorder: a randomized, controlled trial.

Here, we investigated the brain functional connectivity (FC) changes following a novel accelerated theta burst stimulation protocol known as Stanford Neuromodulation Therapy (SNT) which demonstrated significant antidepressant efficacy in treatment-resistant depression (TRD). In a sample of 24 patients (12 active and 12 sham), active stimulation was associated with significant pre- and post-treatment modulation of three FC pairs, involving the default mode network (DMN), amygdala, salience network (SN) and striatum. The most robust finding was the SNT effect on amygdala-DMN FC (group*time interaction F(1,22) = 14.89, p < 0.001). This FC change correlated with improvement in depressive symptoms (rho (Spearman) = -0.45, df = 22, p = 0.026). The post-treatment FC pattern showed a change in the direction of the healthy control group and was sustained at the one-month follow-up. These results are consistent with amygdala-DMN connectivity dysfunction as an underlying mechanism of TRD and bring us closer to the goal of developing imaging biomarkers for TMS treatment optimization.Trial registration: ClinicalTrials.gov NCT03068715.

Real-Time Semi-Automated and Automated Voxel Placement using fMRI Targets for Repeated Acquisition Magnetic Resonance Spectroscopy.

BACKGROUND: Currently, magnetic resonance spectroscopy (MRS) is dependent on the investigative team to manually prescribe, or demarcate, the desired tissue volume-of-interest. The need for a new method to automate precise voxel placements is warranted to improve the utility and interpretability of MRS data. NEW METHOD: We propose and validate robust and real-time methods to automate MRS voxel placement using functionally defined coordinates within the prefrontal cortex. Data were collected and analyzed using two independent prospective studies: 1) two independent imaging days with each consisting of a multi-session sandwich design (MRS data only collected on one of the days determined based on scan time) and 2) a longitudinal design. Participants with fibromyalgia syndrome (N = 50) and major depressive disorder (N = 35) underwent neuroimaging. MRS acquisitions were acquired at 3-tesla. Evaluation of the reproducibility of spatial location and tissue segmentation was assessed for: 1) manual, 2) semi-automated, and 3) automated voxel prescription approaches RESULTS: Variability of voxel grey and white matter tissue composition was reduced using automated placement protocols. Spatially, post- to pre-voxel center-of-gravity distance was reduced and voxel overlap increased significantly across datasets using automated compared to manual procedures COMPARISON WITH EXISTING METHODS: Manual prescription, the current standard in the field, can produce inconsistent data across repeated acquisitions. Using automated voxel placement, we found reduced variability and more consistent voxel placement across multiple acquisitions CONCLUSIONS: These results demonstrate the within subject reliability and reproducibility of a method for reducing variability introduced by spatial inconsistencies during MRS acquisitions. The proposed method is a meaningful advance toward improved consistency of MRS data in neuroscience and can be utilized for multi-session and longitudinal studies.

Exploring Young Adult Comfort with Oral Health Care Providers' Discussions Related to HPV: A mixed methods study.

Purpose: Human papillomavirus (HPV) is the most prevalent sexually transmitted infection in the United States and oral healthcare providers (OHPs) have become increasingly focused on preventing oral health outcomes related to HPV through screening for oral cancer and recommending HPV vaccination. The purpose of this study was to explore the comfort of having HPV-related discussions with OHPs among a college-age population.Methods: Students enrolled in an introductory-level, personal health class at a large, public, mid-Atlantic institution were invited to participate in an anonymous survey. Ten items related to participant's perceptions of HPV discussions with an OHP were part of a larger 100 item online survey designed to measure various aspects of college student health. Comfort with an OHPs' discussion of various health issues (including oral cancer, the relationship between oral cancer and HPV, and HPV vaccination) was measured on a 5-point scale with follow up, open-ended questions. Descriptive statistics were used to analyze the data; thematic coding was used to analyze the open-ended items.Results: A total of 3,236 students were invited to participate during the two data collection waves; 2,198 surveys were fully completed, representing a 67.9% response rate. Participants reported having the greatest level of comfort discussing oral health prevention behaviors such as tooth brushing and flossing and the least comfort discussing HPV-related topics with OHPs. Among those expressing low levels of comfort, qualitative responses highlighted participants limited knowledge related to HPV and the HPV vaccination along with the belief that these discussions were better suited for physicians.Conclusions: Results from this study demonstrated that college-age students may be uncomfortable with HPV-related discussions in a dental care setting. However, given the relationship between HPV infection and poor oral health outcomes, it is important that this population be informed about the oral-systemic HPV relationship and of the HPV vaccination as means for primary prevention. These findings highlight the need to address the public's perceptions regarding the role that OHPs play in educating the public about oral-systemic health.

Nonplanar Spray-Coated Perovskite Solar Cells.

Spray coating is an industrially mature technique used to deposit thin films that combines high throughput with the ability to coat nonplanar surfaces. Here, we explore the use of ultrasonic spray coating to fabricate perovskite solar cells (PSCs) over rigid, nonplanar surfaces without problems caused by solution dewetting and subsequent "run-off". Encouragingly, we find that PSCs can be spray-coated using our processes onto glass substrates held at angles of inclination up to 45° away from the horizontal, with such devices having comparable power conversion efficiencies (up to 18.3%) to those spray-cast onto horizontal substrates. Having established that our process can be used to create PSCs on surfaces that are not horizontal, we fabricate devices over a convex glass substrate, with devices having a maximum power conversion efficiency of 12.5%. To our best knowledge, this study represents the first demonstration of a rigid, curved perovskite solar cell. The integration of perovskite photovoltaics onto curved surfaces will likely find direct applications in the aerospace and automotive sectors.

Gas-Assisted Spray Coating of Perovskite Solar Cells Incorporating Sprayed Self-Assembled Monolayers.

Self-assembled monolayers (SAMs) are becoming widely utilized as hole-selective layers in high-performance p-i-n architecture perovskite solar cells. Ultrasonic spray coating and airbrush coating are demonstrated here as effective methods to deposit MeO-2PACz; a carbazole-based SAM. Potential dewetting of hybrid perovskite precursor solutions from this layer is overcome using optimized solvent rinsing protocols. The use of air-knife gas-quenching is then explored to rapidly remove the volatile solvent from an MAPbI3 precursor film spray-coated onto an MeO-2PACz SAM, allowing fabrication of p-i-n devices with power conversion efficiencies in excess of 20%, with all other layers thermally evaporated. This combination of deposition techniques is consistent with a rapid, roll-to-roll manufacturing process for the fabrication of large-area solar cells.

School Health Service Provider Perceptions on Facilitated Interactive Role-Play Around HPV Vaccine Recommendation.

The purpose of this study was to evaluate a facilitated interactive role-playing activity on increasing human papillomavirus (HPV) vaccine recommendation skills for school nurses and school-based health center staff. A 1-day workshop was implemented for school-based clinicians focused on improving HPV vaccination rates in schools. The workshop included a facilitated interactive role-playing activity involving five scenarios related to recommending the HPV vaccine to parents. Participants completed a usability survey with open-ended questions assessing their experience. A general inductive approach was used to examine responses. Sixteen participants completed the usability survey. The major strength identified specific to the activity included opportunity to practice evidence-based recommendation skills (n = 10). Weaknesses of the activity identified included lack of diversity (n = 4) and complexity within the scenarios (n = 2). Results could shift current educational and clinical paradigms through the implementation of hands-on education strategies to effectively train school-based clinicians to strongly recommend the HPV vaccine.

Stanford Neuromodulation Therapy (SNT): A Double-Blind Randomized Controlled Trial.

OBJECTIVE: Depression is the leading cause of disability worldwide, and half of patients with depression have treatment-resistant depression. Intermittent theta-burst stimulation (iTBS) is approved by the U.S. Food and Drug Administration for the treatment of treatment-resistant depression but is limited by suboptimal efficacy and a 6-week duration. The authors addressed these limitations by developing a neuroscience-informed accelerated iTBS protocol, Stanford neuromodulation therapy (SNT; previously referred to as Stanford accelerated intelligent neuromodulation therapy, or SAINT). This protocol was associated with a remission rate of ∼90% after 5 days of open-label treatment. Here, the authors report the results of a sham-controlled double-blind trial of SNT for treatment-resistant depression. METHODS: Participants with treatment-resistant depression currently experiencing moderate to severe depressive episodes were randomly assigned to receive active or sham SNT. Resting-state functional MRI was used to individually target the region of the left dorsolateral prefrontal cortex most functionally anticorrelated with the subgenual anterior cingulate cortex. The primary outcome was score on the Montgomery-Åsberg Depression Rating Scale (MADRS) 4 weeks after treatment. RESULTS: At the planned interim analysis, 32 participants with treatment-resistant depression had been enrolled, and 29 participants who continued to meet inclusion criteria received either active (N=14) or sham (N=15) SNT. The mean percent reduction from baseline in MADRS score 4 weeks after treatment was 52.5% in the active treatment group and 11.1% in the sham treatment group. CONCLUSIONS: SNT, a high-dose iTBS protocol with functional-connectivity-guided targeting, was more effective than sham stimulation for treatment-resistant depression. Further trials are needed to determine SNT's durability and to compare it with other treatments.

Diltiazem Dosing Strategies in the Management of Atrial Fibrillation With Rapid Ventricular Rate.

Introduction Diltiazem is commonly used for the management of atrial fibrillation (AFIB) with rapid ventricular rate (RVR) in the emergency department (ED). Conflicting studies comparing the efficacy of diltiazem have led to various dosing strategies. The objective of this study was to investigate diltiazem administration in a community ED and determine the effect of varying doses on heart rate (HR) control, systolic blood pressure (SBP) and diastolic blood pressure (DBP). Methods This is a retrospective, single-center study of adult patients treated with diltiazem for AFIB-RVR in the ED between January 1 and December 31, 2019. Inclusion criteria included pretreatment HR > 120 beats per minute (bpm). Patients were administered diltiazem at the discretion of the ED physician. Primary endpoint was time to achieve HR < 100 bpm after diltiazem. Secondary endpoints included mean weight-based dose of diltiazem, percentage of patients achieving HR < 100 bpm within 240 minutes of diltiazem, nadir SBP and nadir DBP. Results Ninety-nine patients were included in the study. Seventy-two percent of patients received ≤ 10 mg diltiazem bolus. Mean weight-based dose of diltiazem bolus was 0.13 mg/kg. Mean time to achieve HR < 100 bpm was 270 minutes for the entire cohort. Patients treated with ≥ 0.13 mg/kg diltiazem achieved an HR < 100 bpm at a mean time of 169 minutes compared to 318 minutes for < 0.13 mg/kg (p = 0.0107). HR control was achieved in 61% of patients who received ≥ 0.13 mg/kg compared to 36% of patients who received < 0.13 mg/kg diltiazem (p = 0.0213). No patients discontinued diltiazem for hypotension or bradycardia. The lowest recorded SBP and DBP within 240 minutes of diltiazem were 90 mmHg and 47 mmHg, respectively. There was no significant difference in the lowest SBP and DBP for patients who received < 0.13 mg/kg compared to ≥ 0.13 mg/mg diltiazem. Conclusion The majority of patients with AFIB RVR received a 10 mg non-weight-based diltiazem bolus dose in the ED. Diltiazem bolus dosing ≥ 0.13 mg/kg was associated with significantly improved times to achieve HR control compared to < 0.13 mg/kg and was not associated with hypotension or bradycardia.

Hypnotic predictors of agency: Responsiveness to specific suggestions in hypnosis is associated with involuntariness in fibromyalgia.

Hypnosis is associated with alterations in the sense of agency which can play a role in its utilization as a nonpharmacological option for pain management. The goal of the current study was to examine the relationships between responsiveness to suggestions in hypnosis and alterations of the sense of agency among patients with fibromyalgia. Ninety-eight participants with fibromyalgia underwent two hypnotizability assessments followed by the Sense of Agency Rating Scale. Clinical pain measures were also collected. Involuntariness was predicted by responsiveness to control, ideomotor, and dissociation suggestions. Effortlessness was predicted by responsiveness to control and ideomotor suggestions, and age. Hypnotizability was associated with main clinical pain outcomes, but agency alterations were not. Results suggest a shared mechanism between responsiveness to specific suggestions and the sense of agency in hypnosis. We discuss theoretical and clinical implications for pain management and the need for further research.

Recoil implantation using gas-phase precursor molecules.

Ion implantation underpins a vast range of devices and technologies that require precise control over the physical, chemical, electronic, magnetic and optical properties of materials. A variant termed "recoil implantation" - in which a precursor is deposited onto a substrate as a thin film and implanted via momentum transfer from incident energetic ions - has a number of compelling advantages, particularly when performed using an inert ion nano-beam [Fröch et al., Nat. Commun., 2020, 11, 5039]. However, a major drawback of this approach is that the implant species are limited to the constituents of solid thin films. Here we overcome this limitation by demonstrating recoil implantation using gas-phase precursors. Specifically, we fabricate nitrogen-vacancy (NV) color centers in diamond using an Ar+ ion beam and the nitrogen-containing precursor gases N2, NH3 and NF3. Our work expands the applicability of recoil implantation with the potential to be suitable to a larger portion of the periodic table, and to applications in which thin film deposition/removal is impractical.

Evaluation of HPV Vaccine: Same Way, Same DayTM: A Pilot Study.

Missed clinical opportunities and the lack of strong and consistent vaccine recommendations are key reasons for low HPV vaccination rates. The purpose of this study was to conduct a pilot evaluation of a web-based training's impact on knowledge, attitudes, and self-efficacy related to providing evidence-based HPV vaccine recommendations. Participants completed three online interactive learning modules and the HPV Vaccine: Same Way, Same Day™ smartphone application (app). Participants completed a pre-training survey, immediate post-training survey, and two-month post-survey. Participants demonstrated a statistically significant increase in knowledge scores from T1 to T2 and T1 to T3. Mean attitudes for recommending HPV vaccination for female patients increased from T1 to T2 and T1 to T3. Mean attitudes for recommending HPV vaccination for male patients increased from T1 to T2 and T1 to T3. Mean self-efficacy scores increased from T1 to T2 and T1 to T3. The HPV Vaccine: Same Way, Same Day™ app is a promising strategy for improving HPV vaccine recommendations among physicians. Future research should explore long-term effects and enroll attending and community physicians to examine its efficacy in other physician populations.

Usability Evaluation of the Novel Smartphone Application, HPV Vaccine: Same Way, Same Day, Among Pediatric Residents.

OBJECTIVE: Scalable, deliberate practice training strategies to administer evidence-based recommendations are necessary to improve human papillomavirus (HPV) vaccination rates. We sought to characterize resident clinicians' perceptions regarding the usability of the HPV Vaccine: Same Way, Same Day smartphone application (app). Usability, a critical aspect of digital programs to promote behavior change, was evaluated. METHODS: Fifteen third-year pediatric residents were recruited to complete a usability evaluation of the HPV Vaccine: Same Way, Same Day app, which includes simulated role-play scenarios in which users interact, as a pediatrician avatar, with an animated parent hesitant to accept the vaccine for her child. The app provides information about the vaccine and utilizes deliberate practice, a purposeful and systematic approach to improve performance, to teach evidence-based vaccine recommendation practices, including motivational interviewing skills. Data were derived from in-depth, semistructured interviews with pediatric residents. We used a constructivist general inductive approach to illuminate perspectives via inductive coding and pattern identification. Garrison's theoretical construct on self-directed learning was used to cluster themes into conceptual categories. RESULTS: We classified interview data in 3 conceptual categories: self-management, internal monitoring and motivational principles. Residents described the app as interactive, easy to use, succinct, informative, engaging, and practical. All residents would recommend the HPV Vaccine: Same Way, Same Day app to a colleague. Residents suggested adding more complex cases for future iterations. CONCLUSIONS: From their perspective, pediatric residents reported that an app using deliberate practice principles has the potential to inform and advance providers' counseling skills regarding the HPV vaccine.

A Methodology for Estimating the Cost of Educating Military Physicians at the Uniformed Services University.

INTRODUCTION: The Department of Defense (DoD) operates a large, multi-channeled physician accession pipeline to maintain a professional workforce of over 10,000 active duty physicians. The Uniformed Services University (USU) operates the nation's only federal medical school providing trained doctors to the Army, Navy, Air Force, and Public Health Service. Although the school serves an essential purpose, policymakers question the cost of operating the University's medical school. One challenge is to develop reproducible and transparent costing methods that can be used to evaluate the University's value and efficiency. METHODS: This work proposes a replicable methodology for estimating the cost per student-year at USU. Using detailed data from USU encompassing facility use, budgeting and expenditures, and faculty and student rosters, we break out and attribute costs to the University's component schools. Using faculty and staff time-use surveys, we further break out education-related personnel costs from other University activities such as research and service. We can then calculate the School of Medicine's annual cost to educate a uniformed physician. RESULTS: In Fiscal Year 2017, it cost the DoD approximately $253,000 per year (more than $1 million dollars total over a 4-year curriculum) to directly educate a physician though the USU School of Medicine. Data from the following Fiscal Year show that education costs grew a modest 2.1% per student-year. CONCLUSIONS: This work provides a foundational framework and approach to estimate the costs of accessioning a physician at USU. This methodology can be replicated for subsequent value analyses of physician accession and retention as budgetary pressures change to match the DoD operating environment. Uniformed Services University's costs should be periodically reassessed against those of alternative accession sources.

Development of Spray-Coated Perovskite Solar Cells.

Over the past six years, researchers have investigated the use of spray coating to fabricate perovskite solar cells (PSCs), with the aim of demonstrating its viability as an industrial manufacturing process. This spotlight on applications outlines the key benefits of this coating technology and summarizes progress made to date, with attention focused on varied efforts to control the crystallization and uniformity of the perovskite layer. The emerging understanding of processes required to create smooth, dense spray-cast perovskite films has recently led to the demonstration of fully spray-cast PSCs with a power conversion efficiency of 19.4%.

Rapid Scalable Processing of Tin Oxide Transport Layers for Perovskite Solar Cells.

The development of scalable deposition methods for perovskite solar cell materials is critical to enable the commercialization of this nascent technology. Herein, we investigate the use and processing of nanoparticle SnO2 films as electron transport layers in perovskite solar cells and develop deposition methods for ultrasonic spray coating and slot-die coating, leading to photovoltaic device efficiencies over 19%. The effects of postprocessing treatments (thermal annealing, UV ozone, and O2 plasma) are then probed using structural and spectroscopic techniques to characterize the nature of the np-SnO2/perovskite interface. We show that a brief "hot air flow" method can be used to replace extended thermal annealing, confirming that this approach is compatible with high-throughput processing. Our results highlight the importance of interface management to minimize nonradiative losses and provide a deeper understanding of the processing requirements for large-area deposition of nanoparticle metal oxides.

Fully Spray-Coated Triple-Cation Perovskite Solar Cells.

We use ultrasonic spray-coating to sequentially deposit thin films of tin oxide, a triple-cation perovskite and spiro-OMeTAD, allowing us fabricate perovskite solar cells (PSCs) with a champion reverse scan power conversion efficiency (PCE) of 19.4% on small-area substrates. We show that the use of spray-deposition permits us to rapidly (>80 mm s-1) coat 25 mm × 75 mm substrates that were divided into a series of devices each with an active area of 15.4 mm2, yielding an average PCE of 10.3% and a peak PCE of 16.3%. By connecting seven 15.4 mm2 devices in parallel on a single substrate, we create a device having an effective active area of 1.08 cm2 and a PCE of 12.7%. This work demonstrates the possibility for spray-coating to fabricate high efficiency and low-cost perovskite solar cells at speed.

Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression.

OBJECTIVE: New antidepressant treatments are needed that are effective, rapid acting, safe, and tolerable. Intermittent theta-burst stimulation (iTBS) is a noninvasive brain stimulation treatment that has been approved by the U.S. Food and Drug Administration for treatment-resistant depression. Recent methodological advances suggest that the current iTBS protocol might be improved through 1) treating patients with multiple sessions per day at optimally spaced intervals, 2) applying a higher overall pulse dose of stimulation, and 3) precision targeting of the left dorsolateral prefrontal cortex (DLPFC) to subgenual anterior cingulate cortex (sgACC) circuit. The authors examined the feasibility, tolerability, and preliminary efficacy of Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT), an accelerated, high-dose resting-state functional connectivity MRI (fcMRI)-guided iTBS protocol for treatment-resistant depression. METHODS: Twenty-two participants with treatment-resistant depression received open-label SAINT. fcMRI was used to individually target the region of the left DLPFC most anticorrelated with sgACC in each participant. Fifty iTBS sessions (1,800 pulses per session, 50-minute intersession interval) were delivered as 10 daily sessions over 5 consecutive days at 90% resting motor threshold (adjusted for cortical depth). Neuropsychological testing was conducted before and after SAINT. RESULTS: One participant withdrew, leaving a sample size of 21. Nineteen of 21 participants (90.5%) met remission criteria (defined as a score <11 on the Montgomery-Åsberg Depression Rating Scale). In the intent-to-treat analysis, 19 of 22 participants (86.4%) met remission criteria. Neuropsychological testing demonstrated no negative cognitive side effects. CONCLUSIONS: SAINT, an accelerated, high-dose, iTBS protocol with fcMRI-guided targeting, was well tolerated and safe. Double-blinded sham-controlled trials are needed to confirm the remission rate observed in this initial study.

Plastic Deformation of Single-Crystal Diamond Nanopillars.

Diamond is known to possess a range of extraordinary properties that include exceptional mechanical stability. In this work, it is demonstrated that nanoscale diamond pillars can undergo not only elastic deformation (and brittle fracture), but also a new form of plastic deformation that depends critically on the nanopillar dimensions and crystallographic orientation of the diamond. The plastic deformation can be explained by the emergence of an ordered allotrope of carbon that is termed O8-carbon. The new phase is predicted by simulations of the deformation dynamics, which show how the sp3 bonds of (001)-oriented diamond restructure into O8-carbon in localized regions of deforming diamond nanopillars. The results demonstrate unprecedented mechanical behavior of diamond, and provide important insights into deformation dynamics of nanostructured materials.

Growth Hormone Alters Brain Morphometry, Connectivity, and Behavior in Subjects with Fatigue after Mild Traumatic Brain Injury.

Pituitary dysfunction with reduced growth hormone (GH) secretion is common in patients following traumatic brain injury (TBI), and these patients often develop chronic symptoms including fatigue and altered cognition. We examined 18 subjects with a history of mild TBI, fatigue, and insufficient GH secretion. Subjects received GH replacement in a year-long, double-blind, placebo-controlled, crossover study, and were assessed for changes in physical performance, body composition, resting energy expenditure, fatigue, sleep, mood, and neuropsychological status. Additionally, magnetic resonance imaging (MRI) was used to assess changes in brain structure and resting state functional connectivity. GH replacement resulted in decreased fatigue, sleep disturbance, and anxiety, as well as increased resting energy expenditure, improved body composition, and altered perception of submaximal effort when performing exercise testing. Associated brain changes included increased frontal cortical thickness and gray matter volume and resting state connectivity changes in regions associated with somatosensory networks. GH replacement altered brain morphology and connectivity and reduced fatigue and related symptoms in mild TBI patients. Additional studies are needed to understand the mechanisms causing TBI-related fatigue and symptom relief with GH replacement.

Altered structural brain network topology in chronic migraine.

Despite its prevalence and high disease burden, the pathophysiological mechanisms underlying chronic migraine (CM) are not well understood. As CM is a complex disorder associated with a range of sensory, cognitive, and affective comorbidities, examining structural network disruption may provide additional insights into CM symptomology beyond studies of focal brain regions. Here, we compared structural interconnections in patients with CM (n = 52) and healthy controls (HC) (n = 48) using MRI measures of cortical thickness and subcortical volume combined with graph theoretical network analyses. The analysis focused on both local (nodal) and global measures of topology to examine network integration, efficiency, centrality, and segregation. Our results indicated that patients with CM had altered global network properties that were characterized as less integrated and efficient (lower global and local efficiency) and more highly segregated (higher transitivity). Patients also demonstrated aberrant local network topology that was less integrated (higher path length), less central (lower closeness centrality), less efficient (lower local efficiency) and less segregated (lower clustering). These network differences not only were most prominent in the limbic and insular cortices but also occurred in frontal, temporal, and brainstem regions, and occurred in the absence of group differences in focal brain regions. Taken together, examining structural correlations between brain areas may be a more sensitive means to detect altered brain structure and understand CM symptomology at the network level. These findings contribute to an increased understanding of structural connectivity in CM and provide a novel approach to potentially track and predict the progression of migraine disorders.This study is registered on ClinicalTrials.gov (Identifier: NCT03304886).