Nanoscale Three-Dimensional Imaging of Integrated Circuits Using a Scanning Electron Microscope and Transition-Edge Sensor Spectrometer.

X-ray nanotomography is a powerful tool for the characterization of nanoscale materials and structures, but it is difficult to implement due to the competing requirements of X-ray flux and spot size. Due to this constraint, state-of-the-art nanotomography is predominantly performed at large synchrotron facilities. We present a laboratory-scale nanotomography instrument that achieves nanoscale spatial resolution while addressing the limitations of conventional tomography tools. The instrument combines the electron beam of a scanning electron microscope (SEM) with the precise, broadband X-ray detection of a superconducting transition-edge sensor (TES) microcalorimeter. The electron beam generates a highly focused X-ray spot on a metal target held micrometers away from the sample of interest, while the TES spectrometer isolates target photons with a high signal-to-noise ratio. This combination of a focused X-ray spot, energy-resolved X-ray detection, and unique system geometry enables nanoscale, element-specific X-ray imaging in a compact footprint. The proof of concept for this approach to X-ray nanotomography is demonstrated by imaging 160 nm features in three dimensions in six layers of a Cu-SiO2 integrated circuit, and a path toward finer resolution and enhanced imaging capabilities is discussed.

LGBTQ+ Inclusivity Training and Education: A Toolkit for Skilled Nursing Facilities.

OBJECTIVES: The objective of this study was to develop the LGBTQ+ Inclusivity Training and Education (LITE) toolkit and to examine the usability and acceptability of the LITE toolkit to health care workers and staff who work within skilled nursing facilities (SNFs). DESIGN: A community-engaged approach using human-centered design to develop the LITE toolkit. To test the usability and acceptability of the LITE toolkit, we provided a posttest survey to users after a 9-week period. SETTING AND PARTICIPANTS: The LITE toolkit was distributed to 25 SNFs throughout a 7-county area in North Carolina. METHODS: Development processes included an LGBTQ+ community advisory board, development of resource topics and a list of best practices, and development of a website. The LITE toolkit comprised a website of LGBTQ+ resources, poster of 6 Best Practices to LGBTQ+ Care, rainbow lapel pins, and writing pens with the LITE logo. Online surveys were distributed to SNF administrators to share with health care workers and staff to collect data on the usability and acceptability of the LITE toolkit. Descriptive statistics were used for data analysis. RESULTS: Fifteen participants completed the survey. Answering all survey questions was not a requirement. Seventy-nine percent (n = 14) of SNF health care workers indicated that the LITE toolkit was "easy to understand" and that they were satisfied with the contents. Fifty-three percent (n = 15) responded that the LITE toolkit would improve the way they care for patients. Sixty-six percent (n = 15) of health care workers and staff strongly agreed the LITE toolkit was applicable to their job role. CONCLUSIONS AND IMPLICATIONS: Providing useful and acceptable LGBTQ+-focused training and education for members of the SNF community addresses the need for health care worker and staff training to foster equitable care and inclusive environments for the LGBTQ+ older adult community. Additional work focused on understanding the facilitators and barriers to using the LITE toolkit in the SNF setting is needed.

Connective Tissue Disorders and Cardiovascular Complications: The Indomitable Role of Transforming Growth Factor-ß Signaling.

Marfan Syndrome (MFS) and Loeys-Dietz Syndrome (LDS) represent heritable connective tissue disorders that segregate with a similar pattern of cardiovascular defects (thoracic aortic aneurysm, mitral valve prolapse/regurgitation, and aortic dilatation with regurgitation). This pattern of cardiovascular defects appears to be expressed along a spectrum of severity in many heritable connective tissue disorders and raises suspicion of a relationship between the normal development of connective tissues and the cardiovascular system. With overwhelming evidence of the involvement of aberrant Transforming Growth Factor-beta (TGF-ß) signaling in MFS and LDS, this signaling pathway may represent the common link in the relationship between connective tissue disorders and their associated cardiovascular complications. To further explore this hypothetical link, this chapter will review the TGF-ß signaling pathway, the heritable connective tissue syndromes related to aberrant TGF-ß signaling, and will discuss the pathogenic contribution of TGF-ß to these syndromes with a primary focus on the cardiovascular system.

NMD abnormalities during brain development in the Fmr1-knockout mouse model of fragile X syndrome.

BACKGROUND: Fragile X syndrome (FXS) is an intellectual disability attributable to loss of fragile X protein (FMRP). We previously demonstrated that FMRP binds mRNAs targeted for nonsense-mediated mRNA decay (NMD) and that FMRP loss results in hyperactivated NMD and inhibition of neuronal differentiation in human stem cells. RESULTS: We show here that NMD is hyperactivated during the development of the cerebral cortex, hippocampus, and cerebellum in the Fmr1-knockout (KO) mouse during embryonic and early postnatal periods. Our findings demonstrate that NMD regulates many neuronal mRNAs that are important for mouse brain development. CONCLUSIONS: We reveal the abnormal regulation of these mRNAs in the Fmr1-KO mouse, a model of FXS, and highlight the importance of early intervention.

Design of a 3000-Pixel Transition-Edge Sensor X-Ray Spectrometer for Microcircuit Tomography.

Feature sizes in integrated circuits have decreased substantially over time, and it has become increasingly difficult to three-dimensionally image these complex circuits after fabrication. This can be important for process development, defect analysis, and detection of unexpected structures in externally sourced chips, among other applications. Here, we report on a non-destructive, tabletop approach that addresses this imaging problem through x-ray tomography, which we uniquely realize with an instrument that combines a scanning electron microscope (SEM) with a transition-edge sensor (TES) x-ray spectrometer. Our approach uses the highly focused SEM electron beam to generate a small x-ray generation region in a carefully designed target layer that is placed over the sample being tested. With the high collection efficiency and resolving power of a TES spectrometer, we can isolate x-rays generated in the target from background and trace their paths through regions of interest in the sample layers, providing information about the various materials along the x-ray paths through their attenuation functions. We have recently demonstrated our approach using a 240 Mo/Cu bilayer TES prototype instrument on a simplified test sample containing features with sizes of ∼ 1 µm. Currently, we are designing and building a 3000 Mo/Au bilayer TES spectrometer upgrade, which is expected to improve the imaging speed by factor of up to 60 through a combination of increased detector number and detector speed.

Adolescents' Sex-Related Alcohol Expectancies and Alcohol Advertisements in Magazines: The Role of Wishful Identification, Realism, and Beliefs about Women's Enjoyment of Sexualization.

In the United States, approximately one in five sexually active teens report alcohol or drug use before their last sexual encounter. The co-occurrence of alcohol with sex increases risky behaviors, such as having unprotected sex. Magazines that target adolescents often feature alcohol advertisements with sexual innuendo and female objectification. Such advertisements may inform adolescents' expectancies that alcohol can facilitate sex. With an experimental design and path analysis, we examined 874 adolescents' (ages 15-17, M = 16.05) exposure to objectifying alcohol ads, their perceptions of the ads, and their attitudes about women's sexualization in relation to sex-related alcohol expectancies. For female adolescents we assessed their enjoyment of sexualization, and for male adolescents, we assessed their perceived enjoyment of sexualization among women. Teens' perceptions that alcohol ads promote the co-occurrence of alcohol with sex mediated the effect of ad exposure and perceived realism of the ads on sex-related alcohol expectancies. The enjoyment of sexualization construct mediated the effect of wishful identification and perceived realism on sex-related alcohol expectancies. Wishful identification also directly related to sex-related alcohol expectancies. Results challenge the alcohol industry's compliance with advertisement regulations and suggest media literacy as a strategy to promote healthy sex-related alcohol expectancies among adolescents.

The Influence of Using a Footstool during a Prolonged Standing Task on Low Back Pain in Office Workers.

While many office workers experience low back pain (LBP), little is known about the effect of prolonged standing on LBP symptoms. This repeated-measures within-subjects study aimed to determine whether office workers with LBP are able to work at a standing workstation for one hour without exacerbating symptoms and whether using a footstool affects LBP severity. Sixteen office workers with LBP performed computer work at a standing workstation for one hour under the following two conditions, one week apart: with a footstool and without a footstool. The intensity of LBP was recorded at 10 min intervals. Maximal severity of LBP pain and change in LBP severity throughout the standing task were not different between the footstool and no footstool conditions (p > 0.26). There was a trend for more participants to have an increase in their pain between the start and end of the task when not using a footstool compared to using a footstool (p = 0.10). Most office workers with LBP are able to use a standing workstation without significant exacerbation of symptoms, but a proportion will experience a clinical meaningful increase in symptoms. Using a footstool does not change the severity of LBP experienced when using a standing workstation in individuals with a history of LBP.

A pressure and shear sensing liner for prosthetic sockets.

Interface pressures are closely related to the comfort and fit of a lower-limb prosthetic socket and clinicians and researchers are interested in monitoring these loads. In particular, shear stresses at the socket/liner interface are indicative of important fit characteristics but are difficult to measure in situ. We have developed an elastomeric liner with sixteen integrated pressure and shear sensors, along with necessary wiring and data acquisition electronics. The sensors measure three-axis pressures using optical emitter/detector pairs coupled with transparent and opaque elastomeric layers. The liner has similar properties to those typically used in clinical practice. The system was tested on a single amputee subject during several sit/stand/walk cycles.

Clinical outcomes associated with the initial use of the Canine Unicompartmental Elbow (CUE) Arthroplasty System(®).

We evaluated mid- to long-term outcomes with respect to function and complications in dogs undergoing canine unicompartmental elbow (CUE) arthroplasty for treatment of medial compartment disease of the elbow. This prospective multicenter case series is the first group of clinical cases to receive CUE arthroplasty. Cases (each elbow that underwent CUE performed by a participating surgeon) were enrolled into an electronic database and prospectively followed to determine and record all associated complications, as well as functional outcomes. There were 103 cases from 18 surgeons. Final follow-up time ranged from 6 to 47 mo with a mean and median of 10 mo. Canine unicompartmental elbow was associated with 1 catastrophic (1%), 11 major (10.7%), and 28 minor (27.2%) complications. Outcomes following CUE were reported as full function in 49 cases (47.6%), acceptable function in 45 cases (43.7%), and unacceptable function in 9 cases (8.7%). We conclude that CUE arthroplasty is an appropriate consideration for treatment of medial compartment disease of the elbow in dogs.

Résultats cliniques associés à l'utilisation initiale du système d'arthroplastieCanine Unicompartmental Elbow (CUE) Arthroplasty SystemMD. Nous avons évalué les résultats à long et à moyen terme relativement à la fonction et aux complications chez les chiens subissant une arthroplastie du coude unicompartimental canin (CUC) pour le traitement de la maladie compartimentale médiale du coude. Cette série prospective de cas multicentres représente le premier groupe de cas cliniques à recevoir une arthroplastie CUC. Les cas (chaque coude qui a subi une CUC réalisée par un chirurgien participant) étaient inscrits dans une base de données électroniques et suivis de manière prospective afin de déterminer et de consigner toutes les complications connexes ainsi que les résultats fonctionnels. Il y avait 103 cas provenant de 18 chirurgiens. Le temps de suivi final s'échelonnait de 6 à 47 mois avec une moyenne et une médiane de 10 mois. Le coude compartimental canin a été associé à 1 complication catastrophique (1 %), à 11 complications majeures (10,7 %) et à 28 complications mineures (27,2 %). Les résultats après l'arthroplastie CUC ont été signalés comme une fonction complète dans 49 cas (47,6 %), une fonction acceptable dans 45 cas (43,7 %) et une fonction inacceptable dans 9 cas (8,7 %). Nous avons conclu que l'arthroplastie CUC est une considération appropriée pour le traitement de la maladie compartimentale médiale du coude chez les chiens.(Traduit par Isabelle Vallières).

Relation of murine thoracic aortic structural and cellular changes with aging to passive and active mechanical properties.

BACKGROUND: Maintenance of the structure and mechanical properties of the thoracic aorta contributes to aortic function and is dependent on the composition of the extracellular matrix and the cellular content within the aortic wall. Age-related alterations in the aorta include changes in cellular content and composition of the extracellular matrix; however, the precise roles of these age-related changes in altering aortic mechanical function are not well understood. METHODS AND RESULTS: Thoracic aortic rings from the descending segment were harvested from C57BL/6 mice aged 6 and 21 months. Thoracic aortic diameter and wall thickness were higher in the old mice. Cellular density was reduced in the medial layer of aortas from the old mice; concomitantly, collagen content was higher in old mice, but elastin content was similar between young and old mice. Stress relaxation, an index of compliance, was reduced in aortas from old mice and correlated with collagen fraction. Contractility of the aortic rings following potassium stimulation was reduced in old versus young mice. Furthermore, collagen gel contraction by aortic smooth muscle cells was reduced with age. CONCLUSIONS: These results demonstrate that numerous age-related structural changes occurred in the thoracic aorta and were related to alterations in mechanical properties. Aortic contractility decreased with age, likely because of a reduction in medial cell number in addition to a smooth muscle contractile deficit. Together, these unique findings provide evidence that the age-related changes in structure and mechanical function coalesce to provide an aortic substrate that may be predisposed to aortopathies.

Connective tissue disorders and cardiovascular complications: the indomitable role of transforming growth factor-beta signaling.

Marfan Syndrome (MFS) and Loeys-Dietz Syndrome (LDS) represent heritable connective tissue disorders that cosegregate with a similar pattern of cardiovascular defects (thoracic aortic aneurysm, mitral valve prolapse/regurgitation, and aortic root dilatation with regurgitation). This pattern of cardiovascular defects appears to be expressed along a spectrum of severity in many heritable connective tissue disorders and raises suspicion of a relationship between the normal development of connective tissues and the cardiovascular system. Given the evidence of increased transforming growth factor-beta (TGF-ß) signaling in MFS and LDS, this signaling pathway may represent the common link in this relationship. To further explore this hypothetical link, this chapter will review the TGF-ß signaling pathway, heritable connective tissue syndromes related to TGF-ß receptor (TGFBR) mutations, and discuss the pathogenic contribution of TGF-ß to these syndromes with a primary focus on the cardiovascular system.

Plasma biomarkers for distinguishing etiologic subtypes of thoracic aortic aneurysm disease.

BACKGROUND: Thoracic aortic aneurysms (TAAs) develop through an asymptomatic process resulting in gross dilation that progresses to rupture if left undetected and untreated. If detected, patients with TAA are followed over time until the risk of rupture outweighs the risk of surgical repair. Current methodologies for tracking TAA size are limited to expensive computed tomography or magnetic resonance imaging because no acceptable population screening tools are currently available. Previous studies from this laboratory and others have identified differential protein profiles for the matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors (TIMPs), in ascending TAA tissue from patients with bicuspid aortic valves (BAVs), versus patients with idiopathic degenerative disease and a tricuspid aortic valve (TAV). In addition, altered microRNA (miR) expression levels have also been reported in TAAs compared with normal aortic tissue. The objective of our study was to identify circulating factors within plasma that could serve as potential biomarkers for distinguishing etiologic subtypes of aneurysm disease. METHODS: Ascending TAA tissue and plasma specimens were obtained from patients with BAV (n = 21) and TAV (n = 21) at the time of surgical resection. The protein abundance of key MMPs (1, 2, 3, 8, and 9), TIMPs (1, 2, 3, and 4), and miRs (1, 21, 29a, 133a, 143, and 145) was examined using a multianalyte protein profiling system or by quantitative polymerase chain reaction, respectively. Results were compared with normal aortic tissue and plasma obtained from patients without aortic disease (n = 10). RESULTS: Significant (P < .05) differences in standardized miR-1 and miR-21 abundance between BAV and TAV aortic tissue samples and different tissue and plasma profiles of analyte differences from normal aorta where observed between the BAV and TAV groups. Linear regression analysis revealed significant linear relationships in plasma and tissue measurements only for MMP-8 and TIMP-1, TIMP-3, and TIMP-4 (P < .05). Receiver operator curve analysis revealed specific cassettes of analytes predictive of TAA disease. Relative to normal aorta, BAV proteolytic balance was significantly increased for MMP-1, MMP-2, and MMP-7, and for decreased MMP-8 and MMP-9. In contrast, TAV proteolytic balance relative to normal aorta was significantly increased only for MMP-1 and decreased for MMP-8 and MMP-9. CONCLUSIONS: Taken together, these unique data demonstrate differential plasma profiles of MMPs, TIMPs, and miRs in ascending TAA specimens from patients with BAV and TAV. These results suggest that circulating biomarkers may form the foundation for a broader platform of biomarkers capable of detecting the presence of TAA using a simple blood test and may also be useful in personalized strategies to distinguish between etiologic subtypes of TAAs in patients with aneurysm disease.

Epidemiology of esophageal cancer.

This article discusses the incidence, geographic differences, and risk factors for the 2 most common cancers of the esophagus: squamous cell and adenocarcinoma.

Static and cyclic performance evaluation of sensors for human interface pressure measurement.

Researchers and clinicians often desire to monitor pressure distributions on soft tissues at interfaces to mechanical devices such as prosthetics, orthotics or shoes. The most common type of sensor used for this type of applications is a Force Sensitive Resistor (FSR) as these are convenient to use and inexpensive. Several other types of sensors exist that may have superior sensing performance but are less ubiquitous or more expensive, such as optical or capacitive sensors. We tested five sensors (two FSRs, one optical, one capacitive and one fluid pressure) in a static drift and cyclic loading configuration. The results show that relative to the important performance characteristics for soft tissue pressure monitoring (i.e. hysteresis, drift), many of the sensors tested have significant limitations. The FSRs exhibited hysteresis, drift and loss of sensitivity under cyclic loading. The capacitive sensor had substantial drift. The optical sensor had some hysteresis and temperature-related drift. The fluid pressure sensor performed well in these tests but is not as flat as the other sensors and is not commercially available. Researchers and clinicians should carefully consider the convenience and performance trade-offs when choosing a sensor for soft-tissue pressure monitoring.

Real-time knee adduction moment feedback for gait retraining through visual and tactile displays.

The external knee adduction moment (KAM) measured during gait is an indicator of tibiofemoral joint osteoarthritis progression and various strategies have been proposed to lower it. Gait retraining has been shown to be an effective, noninvasive approach for lowering the KAM. We present a new gait retraining approach in which the KAM is fed back to subjects in real-time during ambulation. A study was conducted in which 16 healthy subjects learned to alter gait patterns to lower the KAM through visual or tactile (vibration) feedback. Participants converged on a comfortable gait in just a few minutes by using the feedback to iterate on various kinematic modifications. All subjects adopted altered gait patterns with lower KAM compared with normal ambulation (average reduction of 20.7%). Tactile and visual feedbacks were equally effective for real-time training, although subjects using tactile feedback took longer to converge on an acceptable gait. This study shows that real-time feedback of the KAM can greatly increase the effectiveness and efficiency of subject-specific gait retraining compared with conventional methods.

MEMS-based bubble pressure sensor for prosthetic socket interface pressure measurement.

The ability to chronically monitor pressure at the prosthetic socket/residual limb interface could provide important data to the research and clinical communities. With this application in mind, we describe a novel type of sensor which consists of a MEMS pressure sensor and custom electronics packaged in a fluid-filled bubble. The sensor is characterized and compared to two commercially-available technologies. The bubble sensor has excellent drift performance and good sensing resolution. It exhibits hysteresis which may be due to the silicone that the sensor is molded in. To reduce hysteresis, it may be advisable to place the sensor between the liner and the socket rather molding directly into the liner.

Surgical views: Vacuum-assisted wound closure: clinical applications.

Vacuum-assisted closure (VAC) is a wound management system that exposes a wound bed to local negative pressure to promote healing. Benefits of VAC therapy include removal of fluid from the extravascular space, improved circulation, enhanced granulation tissue formation, and increased bacterial clearance. VAC therapy has been used extensively in human patients to treat a variety of acute and chronic wound conditions. This article reviews the use of VAC therapy in a variety of wound conditions and describes our experiences with using VAC therapy in dogs and cats at the University of Florida.

Investigation of rotational skin stretch for proprioceptive feedback with application to myoelectric systems.

We present a new wearable haptic device that provides a sense of position and motion by inducing rotational skin stretch on the user's skin. In the experiments described in this paper, the device was used to provide proprioceptive feedback from a virtual prosthetic arm controlled with myoelectric sensors on the bicep and tricep muscles in 15 able-bodied participants. Targeting errors in blind movements with the haptic device were compared to cases where no feedback and contralateral proprioception were provided. Average errors were lower with the device than with no feedback but larger than with contralateral proprioceptive feedback. Participants also had lower visual demand with the device than with no feedback while tracking a 30 ( degrees ) moving range. The results indicate that the rotational skin stretch may ultimately be effective for proprioceptive feedback in myoelectric prostheses, particularly when vision is otherwise occupied.

Reconstruction and EMG-informed control, simulation and analysis of human movement for athletics: performance improvement and injury prevention.

In this paper we present methods to track and characterize human dynamic skills using motion capture and electromographic sensing. These methods are based on task-space control to obtain the joint kinematics and extract the key physiological parameters and on computed muscle control to solve the muscle force distribution problem. We also present a dynamic control and analysis framework that integrates these metrics for the purpose of reconstructing and analyzing sports motions in real-time.