First Demonstration of Electrostatic Damping of Parametric Instability at Advanced LIGO.

Interferometric gravitational wave detectors operate with high optical power in their arms in order to achieve high shot-noise limited strain sensitivity. A significant limitation to increasing the optical power is the phenomenon of three-mode parametric instabilities, in which the laser field in the arm cavities is scattered into higher-order optical modes by acoustic modes of the cavity mirrors. The optical modes can further drive the acoustic modes via radiation pressure, potentially producing an exponential buildup. One proposed technique to stabilize parametric instability is active damping of acoustic modes. We report here the first demonstration of damping a parametrically unstable mode using active feedback forces on the cavity mirror. A 15 538 Hz mode that grew exponentially with a time constant of 182 sec was damped using electrostatic actuation, with a resulting decay time constant of 23 sec. An average control force of 0.03 nN was required to maintain the acoustic mode at its minimum amplitude.

Exploiting highly ordered subnanoliter volume microcapillaries as microtools for the analysis of antibody producing cells.

The interrogation of highly diverse repertoires of heterogeneous cell populations on a single cell basis increases the likelihood that a cell with unique characteristics will be identified. We have developed a new single cell analysis system comprising millions of bundled subnanoliter volume bioincubation chambers for the identification and recovery of target specific antibody secreting cells (ASCs). This platform integrates dual surface screening with dedicated user driven data analysis and automated cell recovery enabling multiple biophysical parameters to be tracked for millions of antibody leads in parallel. This direct clone analysis and selection technology is a clear deviation from current microfabricated well-based approaches and offers drastically enhanced screening throughput, simultaneous dual surface analysis, and rapid automated single cell recovery. The technology is also applicable to screening both bacterial and mammalian antibody secreting cells. We demonstrate the implementation and feasibility of this platform in identifying target specific antibodies from bacterial, hybridoma, and B cell libraries.

Survey of Resources in Behavioral Sleep Medicine Across the Department of Defense, Defense Health Agency.

INTRODUCTION: Insomnia affects approximately 40% of active duty service members and adversely affects health, readiness, and safety. The VA/DoD Clinical Practice Guideline for the management of insomnia recommends cognitive-behavioral treatment of insomnia (CBTI) or its abbreviated version (brief behavioral treatment of insomnia [BBTI]) as the first-line insomnia treatment. The goal of this study was to assess CBTI/BBTI resources at MTFs, perceived facilitators and barriers for CBTI/BBTI, and gaps in these treatments across the Defense Health Agency. MATERIALS AND METHODS: Between July and October 2022, we conducted an electronic survey of CBTI/BBTI resources across Contiguous United States and the District of Columbia (CONUS) and Outside Continental United States (OCONUS) MTFs. The survey was distributed to 154 military sleep health care providers from 32 MTFs, and a link to the survey was posted on two online military sleep medicine discussion forums. Fifteen providers from 12 MTFs volunteered to complete a 30-minute qualitative interview to explore their perception of barriers and facilitators of CBTI/BBTI at their facility. RESULTS: Fifty-two of 154 providers (33.8%) at 20 MTFs completed the survey. A majority of providers indicated that hypnotics remain the most common treatment for insomnia at their facility. Sixty-eight percent reported that CBTI/BBTI was available at their facility and estimated that less than 50% of the patients diagnosed with insomnia receive CBTI/BBTI. The main facilitators were dedicated, trained CBTI/BBTI providers and leadership support. Referrals to the off-post civilian network and self-help apps were not perceived as significant facilitators for augmenting insomnia care capabilities. The primary barriers to offering CBTI/BBTI were under-resourced clinics to meet the high volume of patients presenting with insomnia and scheduling and workflow limitations that impede repeated treatment appointments over the period prescribed by CBTI/BBTI protocols. Four primary themes emerged from qualitative interviews: (1) CBTI/BBTI groups can scale access to insomnia care, but patient engagement and clinical outcomes are perceived as inferior to individual treatment; (2) embedding trained providers in primary or behavioral health care could accelerate access, before escalation and referral to a sleep clinic; (3) few providers have the time to adhere to traditional CBTI protocols, and appointment scheduling often does not support weekly or bi-weekly treatment visits; and (4) the absence of quality and/or continuity of care measures dampens providers' enthusiasm for using external referral resources or self-help apps. CONCLUSIONS: Although there is a wide recognition that CBTI/BBTI is the first-line recommended insomnia treatment, the limited scalability of treatment protocols, clinical workflow limitations, and scarcity of trained CBTI/BBTI providers limit the implementation of the VA/DoD clinical guideline. Educating and engaging health care providers and leadership about CBTI, augmenting CBTI-dedicated resources, and adapting clinical workflows were identified as specific strategies needed to meet the current insomnia care needs of service members. Developing protocols for scaling the availability of CBTI expertise at diverse points of care, upstream from the sleep clinics, could accelerate access to care. Establishing standardized quality measures and processes across points of care, including for external providers and self-help apps, would enhance providers' confidence in the quality of insomnia care offered to service members.

Digital CBTI hubs as a treatment augmentation strategy in military clinics: study protocol for a pragmatic randomized clinical trial.

BACKGROUND: Chronic insomnia is the most prevalent sleep disorder among military service members, and it compromises readiness, performance, and physical and mental health. Cognitive behavioral treatment for insomnia (CBTI) is the standard of care for the treatment of insomnia recommended by the VA/DoD Clinical Practice Guideline, the American Academy of Sleep Medicine, and the American College of Physicians. CBTI is highly effective but has limited scalability. It is often unavailable in clinical settings where service members receive sleep care. Digital technologies offer unique opportunities to scale and broaden the geographic reach of CBTI services and support increased patient access and engagement in behavioral sleep care. This study aims to evaluate the impact and acceptability of digital CBTI hubs to augment military treatment facilities' capabilities in behavioral sleep medicine. METHODS: This is a multi-site, non-inferiority randomized clinical trial designed to compare the effects of in-person (face-to-face or virtual) insomnia care as usual at three military sleep clinics versus CBTI delivered remotely and asynchronously through digital CBTI hubs. Digital CBTI hubs are led by licensed, certified clinicians who use NOCTEM's® evidence-based clinical decision support platform COAST™ (Clinician Operated Assistive Sleep Technology). Changes in insomnia severity and daytime symptoms of depression and anxiety will be compared at baseline, at 6-8 weeks, and at 3-month follow-up. Patient satisfaction with insomnia care as usual versus digital CBTI hubs will also be examined. We hypothesize that digital CBTI hubs will be non-inferior to insomnia care as usual for improvements in insomnia and daytime symptoms as well as patient satisfaction with insomnia care. DISCUSSION: Digital technology has a high potential to scale CBTI accessibility and delivery options required to meet the insomnia care needs of military service members. Digital CBTI hubs using COAST offer a novel approach to broaden service members' access to CBTI and to serve as an augmentation strategy for existing sleep services at military treatment facilities. The pragmatic approach leveraging technology in this trial has the potential to rapidly inform clinical practice within the Defense Health Agency as well as other healthcare systems. TRIAL REGISTRATION: ClinicalTrials.gov NCT05490550. Registered on 14 July 2023.

Performance comparison of peripheral arterial tonometry-based testing and polysomnography to diagnose obstructive sleep apnea in military personnel.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is increasingly common among military personnel, but diagnostic capabilities are challenged by limited capability for polysomnography (PSG). We sought to evaluate the diagnostic properties of peripheral arterial tonometry (PAT)-based home sleep apnea testing (HSAT) to accurately identify and classify OSA among active-duty military personnel. METHODS: This study was a retrospective review of all patients suspected of having OSA who completed an initial PAT-based HSAT followed by confirmatory PSG within 120 days. The diagnostic properties of a PAT-based, HSAT-derived apnea-hypopnea index (AHI) vs a PSG-derived AHI were assessed. RESULTS: Two hundred eight matched pairs of asynchronous studies were analyzed. The prevalence of OSA was 63.5%. PAT-based HSAT overdiagnosed 27.4% of patients with OSA and underdiagnosed 46.6% of patients with OSA. The majority (n = 116, 55.8%) of patients changed OSA severity classification (absent, mild, moderate, severe) after PSG. OSA severity classification concordance between PAT-based HSAT and PSG was observed in 53.4%, 40.5%, 28.6%, and 40.0% of patients with absent, mild, moderate, and severe OSA, respectively. Receiver operating characteristic curve analysis showed an area under the curve of 0.715 and a proposed PAT-based, HSAT-derived AHI cutoff score for OSA diagnosis of 9.0 events/h. This PAT-based, HSAT-derived AHI provided a 52% sensitivity, 83% specificity, 84% positive predictive value, and 50% negative predictive value. Bland-Altman plots showed an unacceptable degree of agreement between PAT-based, HSAT-derived AHI and AHI. CONCLUSIONS: There is significant discordance between PAT-based HSAT and PSG among active-duty military personnel evaluated for OSA. PAT-based HSAT may have limited utility for diagnosing OSA and grading severity in this unique patient population. CITATION: O'Reilly BM, Wang Q, Collen J, Matsangas P, Colombo CJ, Mysliwiec V. Performance comparison of peripheral arterial tonometry-based testing and polysomnography to diagnose obstructive sleep apnea in military personnel. J Clin Sleep Med. 2022;18(6):1523-1530.

Enhancing behavioral sleep care with digital technology: study protocol for a hybrid type 3 implementation-effectiveness randomized trial.

BACKGROUND: Insomnia affects almost one in four military service members and veterans. The first-line recommended treatment for insomnia is cognitive-behavioral therapy for insomnia (CBTI). CBTI is typically delivered in-person or online over one-to-four sessions (brief versions) or five-to-eight sessions (standard versions) by a licensed doctoral or masters-level clinician with extensive training in behavioral sleep medicine. Despite its effectiveness, CBTI has limited scalability. Three main factors inhibit access to and delivery of CBTI including restricted availability of clinical expertise; rigid, resource-intensive treatment formats; and limited capacities for just-in-time monitoring and treatment personalization. Digital technologies offer a unique opportunity to overcome these challenges by providing scalable, personalized, resource-sensitive, adaptive, and cost-effective approaches for evidence-based insomnia treatment. METHODS: This is a hybrid type 3 implementation-effectiveness randomized trial using a scalable evidence-based digital health software platform, NOCTEM™'s Clinician-Operated Assistive Sleep Technology (COAST™). COAST includes a clinician portal and a patient app, and it utilizes algorithms that facilitate detection of sleep disordered patterns, support clinical decision-making, and personalize sleep interventions. The first aim is to compare three clinician- and system-centered implementation strategies on the reach, adoption, and sustainability of the COAST digital platform by offering (1) COAST only, (2) COAST plus external facilitation (EF: assistance and consultation to providers by NOCTEM's sleep experts), or (3) COAST plus EF and internal facilitation (EF/IF: assistance/consultation to providers by NOCTEM's sleep experts and local champions). The second aim is to quantify improvements in insomnia among patients who receive behavioral sleep care via the COAST platform. We hypothesize that reach, adoption, and sustainability and the magnitude of improvements in insomnia will be superior in the EF and EF/IF groups relative to the COAST-only group. DISCUSSION: Digital health technologies and machine learning-assisted clinical decision support tools have substantial potential for scaling access to insomnia treatment. This can augment the scalability and cost-effectiveness of CBTI without compromising patient outcomes. Engaging providers, stakeholders, patients, and decision-makers is key in identifying strategies to support the deployment of digital health technologies that can promote quality care and result in clinically meaningful sleep improvements, positive systemic change, and enhanced readiness and health among service members. TRIAL REGISTRATION: ClinicalTrials.gov NCT04366284 . Registered on 28 April 2020.

Development of a high sensitivity rapid sandwich ELISA procedure and its comparison with the conventional approach.

A highly sensitive and rapid sandwich enzyme-linked immunosorbent assay (ELISA) procedure was developed for the detection of human fetuin A/AHSG (alpha2-HS-glycoprotein), a specific biomarker for hepatocellular carcinoma and atherosclerosis. Anti-human fetuin A antibody was immobilized on aminopropyltriethoxysilane-mediated amine-functionalized microtiter plates using 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride and N-hydroxysulfosuccinimide-based heterobifunctional cross-linking. The analytical sensitivity of the developed assay was 39 pg/mL, compared to 625 pg/mL for the conventional assay. The generic nature of the developed procedure was demonstrated by performing human fetuin A assays on different polymeric matrixes, i.e., polystyrene, poly(methyl methacrylate), and polycyclo-olefin (Zeonex), in a modified microtiter plate format. Thus, the newly developed procedure has considerable advantages over the existing method.

An experimental and computational investigation of the material behaviour of discrete homogenous iliofemoral and carotid atherosclerotic plaque constituents.

An enhanced understanding of the structure and mechanical behavior of atherosclerotic plaque can potentially provide key guidance for clinical intervention and vascular device design. This study presents an investigation of morphological and mechanical properties of iliofemoral (n = 8) and carotid (n = 22) atherosclerotic plaque constituents. µCT analysis is used characterize the content and morphology of calcifications in excised plaques. Calcified particles contribute a significant proportion of the average plaque volume (7.6% carotid; 19.1% iliofemoral), and on average over 50% of this volume (53.7 ± 18.6% carotid; 61.7 ± 15% iliofemoral) is accounted for by the largest individual particle found in the plaque. Fibrous tissue and calcifications were isolated for mechanical testing. Unconfined compression testing of isolated calcifications uncovered viscoelastic behavior. Tensile stress relaxation uncovered viscoelastic behavior in fibrous atherosclerotic samples. Iliofemoral fibrous samples were found to be statistically significantly stiffer (*p < 0.05) than carotid fibrous samples. Results show isolated calcifications are approximately two orders of magnitude stiffer than non-calcified fibrous tissue. The results from this study advance the current understanding of plaque mechanics and suggest that computational simulation of angioplasty procedures should incorporate a discrete representation of atherosclerotic plaque constituents.

Trauma associated sleep disorder: A parasomnia induced by trauma.

Nightmares and disruptive nocturnal behaviors that develop after traumatic experiences have long been recognized as having different clinical characteristics that overlap with other established parasomnia diagnoses. The inciting experience is typically in the setting of extreme traumatic stress coupled with periods of sleep disruption and/or deprivation. The limited number of laboratory documented cases and symptomatic overlap with rapid eye movement sleep behavior disorder (RBD) and posttraumatic stress disorder (PTSD) have contributed to difficulties in identifying what is a unique parasomnia. Trauma associated sleep disorder (TSD) incorporates the inciting traumatic experience and clinical features of trauma related nightmares and disruptive nocturnal behaviors as a novel parasomnia. The aims of this theoretical review are to 1) summarize the known cases and clinical findings supporting TSD, 2) differentiate TSD from clinical disorders with which it has overlapping features, 3) propose criteria for the diagnosis of TSD, and 4) present a hypothetical neurobiological model for the pathophysiology of TSD. Hyperarousal, as opposed to neurodegenerative changes in RBD, is a component of TSD that likely contributes to overriding atonia during REM sleep and the comorbid diagnosis of insomnia. Lastly, a way forward to further establish TSD as an accepted sleep disorder is proposed.

Adherence to positive airway pressure therapy in U.S. military personnel with sleep apnea improves sleepiness, sleep quality, and depressive symptoms.

OBJECTIVES: Obstructive sleep apnea (OSA) is frequently diagnosed in U.S. military personnel. OSA is associated with sleepiness, poor sleep quality, and service-related illnesses of insomnia, depression, post-traumatic stress disorder, and traumatic brain injury. METHODS: Observational study of active duty military personnel with OSA and adherence to positive airway pressure (PAP) assessed with smart chip technology. RESULTS: 58 men with mean age 36.2 ± 7.7 years, mean body mass index 31.4 ± 3.7 with mean apnea-hypopnea index (AHI) 19.1 ± 19.0 are reported. 23 (39.7%) participants were adherent to PAP, and 35 (60.3%) were nonadherent. No significant differences in baseline demographics, apnea-hypopnea index, service-related illnesses, or clinical instrument scores. Military personnel adherent to PAP had significantly improved sleepiness (p = 0.007), sleep quality (p = 0.013), depressive symptoms (p = 0.01), energy/fatigue (p = 0.027), and emotional well-being (p = 0.024). Participants with moderate-severe OSA were more likely to be in the adherent group when compared with participants diagnosed with mild OSA. CONCLUSIONS: Military personnel with OSA have low adherence to PAP. Adherence is associated with improved depressive symptoms, sleepiness, sleep quality, energy/fatigue, emotional well-being, and social functioning. Future research should focus on interventions to improve the management of OSA in military personnel.

A Comparative Analysis of Sleep Disordered Breathing in Active Duty Service Members with and without Combat-Related Posttraumatic Stress Disorder.

STUDY OBJECTIVES: Posttraumatic stress disorder (PTSD) and obstructive sleep apnea (OSA) are frequently co-occurring illnesses. The purpose of this study was to determine whether comorbid PTSD/OSA is associated with increased PTSD symptoms or decreased OSA severity compared to PTSD or OSA alone in recently deployed Active Duty Service Members (ADSM). METHODS: Cross-sectional observational study of ADSM who returned from combat within 24 months. Participants underwent an attended diagnostic polysomnogram and were assessed for PTSD, depression, combat exposure severity, sleepiness, and sleep quality with validated clinical instruments. RESULTS: Our study included 109 military personnel who returned from a combat deployment within 24 months with a mean age of 34.3 ± 8.23 and BMI of 30.8 ± 3.99. Twenty-four participants had PTSD/OSA, 68 had OSA, and 17 had PTSD. Mean PTSD Checklist- Military Version (PCL-M) scores were 62.0 ± 8.95, 60.5 ± 4.73, and 32.5 ± 8.95 in PTSD/OSA, PTSD, and OSA, respectively. The mean AHI was 16.9 ± 15.0, 18.9 ± 17.0, and 1.73 ± 1.3 for those with PTSD/OSA, OSA, and PTSD. PTSD symptoms and OSA severity in military personnel with comorbid PTSD/OSA were not significantly different from those with PTSD or OSA alone. On multivariate analysis, BMI was a significant predictor of OSA (OR, 1.21; 95% CI, 1.04-1.44) and age trended towards significance. Depression, but not OSA severity, was associated with PTSD symptoms. CONCLUSIONS: Following recent combat exposure, comorbid PTSD/OSA is not associated with increased PTSD symptoms or decreased severity of OSA. Early evaluation after traumatic exposure for comorbid OSA is indicated in PTSD patients with sleep complaints given the high co-occurrence and adverse clinical implications.

Correlation of growth factor receptor expression with clinical growth in vestibular schwannomas.

OBJECTIVE: To examine the relationship between growth rate of vestibular schwannomas and the expression of various growth factor receptors. STUDY DESIGN: Retrospective case review of clinical growth rate in conjunction with a histopathologic and immunohistochemical reexamination of archival specimens. SETTING: A tertiary referral neurotologic center. PATIENTS: Three groups: a historical group to act as controls, consisting of 30 patients with sporadic vestibular schwannomas removed before the unit adopted an initial interval scan policy; a group of 14 patients with sporadic vestibular schwannomas who had undergone an initial interval scan policy, showed radiologic evidence of growth, and therefore had their schwannoma removed; and a group of 16 schwannomas removed from 11 neurofibromatosis Type 2 patients. MAIN OUTCOME MEASURES: A comparison between the three clinical groups using immunohistochemical studies to determine the level of expression of the proliferation factor Ki-67, c-erbB-2, and c-erbB-3 receptors and fibroblastic growth factor receptors 1 and 4. RESULTS: The level of expression of the proliferation factor Ki-67 was very low and similar in all three groups. C-erbB-2 and c-erbB-3 receptors were not expressed in any of the groups. fibroblastic growth factor receptor 4 expression was not significantly different, but there was a variation in the expression of fibroblastic growth factor receptor 1 between the three groups that correlated well with the differing incidence of growth in the groups. The increase in expression of fibroblastic growth factor receptor 1 in the neurofibromatosis Type 2 group was not statistically significant, but the increase in expression of fibroblastic growth factor receptor 1 in the growing sporadic group was statistically significant when compared with the historical controls. The level of fibroblastic growth factor receptor 1 expression correlates significantly with the rate of growth as measured on interval magnetic resonance imaging. CONCLUSIONS: Overexpression of fibroblastic growth factor receptor 1 has a positive correlation with the incidence and the rate of growth of sporadic vestibular schwannomas.

Trauma associated sleep disorder: a proposed parasomnia encompassing disruptive nocturnal behaviors, nightmares, and REM without atonia in trauma survivors.

STUDY OBJECTIVES: To characterize the clinical, polysomnographic and treatment responses of patients with disruptive nocturnal behaviors (DNB) and nightmares following traumatic experiences. METHODS: A case series of four young male, active duty U.S. Army Soldiers who presented with DNB and trauma related nightmares. Patients underwent a clinical evaluation in a sleep medicine clinic, attended overnight polysomnogram (PSG) and received treatment. We report pertinent clinical and PSG findings from our patients and review prior literature on sleep disturbances in trauma survivors. RESULTS: DNB ranged from vocalizations, somnambulism to combative behaviors that injured bed partners. Nightmares were replays of the patient's traumatic experiences. All patients had REM without atonia during polysomnography; one patient had DNB and a nightmare captured during REM sleep. Prazosin improved DNB and nightmares in all patients. CONCLUSIONS: We propose Trauma associated Sleep Disorder (TSD) as a unique sleep disorder encompassing the clinical features, PSG findings, and treatment responses of patients with DNB, nightmares, and REM without atonia after trauma.

Simple approach to study biomolecule adsorption in polymeric microfluidic channels.

Herein a simple analytical method is presented for the characterization of biomolecule adsorption on cyclo olefin polymer (COP, trade name: Zeonor(®)) substrates which are widely used in microfluidic lab-on-a-chip devices. These Zeonor(®) substrates do not possess native functional groups for specific reactions with biomolecules. Therefore, depending on the application, such substrates must be functionalized by surface chemistry methods to either enhance or suppress biomolecular adsorption. This work demonstrates a microfluidic method for evaluating the adsorption of antibodies and oligonucleotides surfaces. The method uses centrifugal microfluidic flow-through chips and can easily be implemented using common equipment such as a spin coater. The working principle is very simple. The user adds 40 L of the solution containing the sample to the starting side of a microfluidic channel, where it is moved through by centrifugal force. Some molecules are adsorbed in the channel. The sample is then collected at the other end in a small reservoir and the biomolecule concentration is measured. As a pilot application, we characterized the adsorption of goat anti-human IgG and a 20-mer DNA on Zeonor(®), and on three types of functionalized Zeonor: 3-aminopropyltriethoxysilane (APTES) modified surface with mainly positive charge, negatively charged surface with immobilized bovine serum albumin (BSA), and neutral, hydrogel-like film with polyethylene glycol (PEG) characteristics. This simple analytical approach adds to the fundamental understanding of the interaction forces in real, microfluidic systems. This method provides a straightforward and rapid way to screen surface compositions and chemistry, and relate these to their effects on the sensitivity and resistance to non-specific binding of bioassays using them. In an additional set of experiments, the surface area of the channels in this universal microfluidic chip was increased by precision milling of microscale trenches. This modified surface was then coated with APTES and tested for its potential to serve as a unique protein dilution feature.

Objective method of assessing and presenting the House-Brackmann and regional grades of facial palsy by production of a facogram.

OBJECTIVE: To produce a reliable objective method of assessing the House-Brackmann (H-B) and regional grades of facial palsy with the results produced and presented in a time and manner suitable for a routine clinical setting. STUDY DESIGN: Analysis of video pixel data using artificial neural networks (ANNs). SETTING: Tertiary-referral neuro-otologic center. SUBJECTS: Subjects with varying degrees of unilateral facial palsy. METHOD: Clinicians assessed videos of subjects with varying degrees of facial palsy performing prescribed movements. The results of their overall and regional assessments were used to train ANNs. These were then tested for consistency, accuracy, and ability to identify clinical changes in grading. RESULTS: A group of subjects had their objective computer assessment repeated, and consistent H-B and regional grades were obtained. A second group had both subjective clinical and objective computer assessments performed. The program gave results that were within the expected level of agreement with the subjective clinical assessment for both H-B and regional grades. A third group had repeated clinical and computer assessments from the time of onset to recovery of facial function. The changes in the computer results both for H-B and regional grades tracked the clinical change. CONCLUSION: It is possible to measure consistently and objectively the H-B and regional grades of facial palsy using trained ANNs to analysis video pixel data, and this can be done in a routine clinical environment by a technician. The results from each region of the face are presented as a Facogram along with the H-B grade.