Polyimide-On-Silicon 2D Piezoelectric Micromachined Ultrasound Transducer (PMUT) Array.

This paper presents a fully addressable 8 × 8 two-dimensional (2D) rigid piezoelectric micromachined ultrasonic transducer (PMUT) array. The PMUTs were fabricated on a standard silicon wafer, resulting in a low-cost solution for ultrasound imaging. A polyimide layer is used as the passive layer in the PMUT membranes on top of the active piezoelectric layer. The PMUT membranes are realized by backside deep reactive ion etching (DRIE) with an oxide etch stop. The polyimide passive layer enables high resonance frequencies that can be easily tuned by controlling the thickness of the polyimide. The fabricated PMUT with 6 µm polyimide thickness showed a 3.2 MHz in-air frequency with a 3 nm/V sensitivity. The PMUT has shown an effective coupling coefficient of 14% as calculated from the impedance analysis. An approximately 1% interelement crosstalk between the PMUT elements in one array is observed, which is at least a five-fold reduction compared to the state of the art. A pressure response of 40 Pa/V at 5 mm was measured underwater using a hydrophone while exciting a single PMUT element. A single-pulse response captured using the hydrophone suggested a 70% -6 dB fractional bandwidth for the 1.7 MHz center frequency. The demonstrated results have the potential to enable imaging and sensing applications in shallow-depth regions, subject to some optimization.

Population health management of low-density lipoprotein cholesterol via a remote, algorithmic, navigator-executed program.

BACKGROUND: Implementation of guideline-directed cholesterol management remains low despite definitive evidence establishing such measures reduce cardiovascular (CV) events, especially in high atherosclerotic CV disease (ASCVD) risk patients. Modern electronic resources now exist that may help improve health care delivery. While electronic medical records (EMR) allow for population health screening, the potential for coupling EMR screening to remotely delivered algorithmic population-based management has been less studied as a way of overcoming barriers to optimal cholesterol management. METHODS: In an academically affiliated healthcare system, using EMR screening, we sought to identify 1,000 high ASCVD risk patients not meeting guideline-directed low-density lipoprotein-cholesterol (LDL-C) goals within specific system-affiliated primary care practices. Contacted patients received cholesterol education and were offered a remote, guideline-directed, algorithmic cholesterol management program executed by trained but non-licensed "navigators" under professional supervision. Navigators used telephone, proprietary software and internet resources to facilitate algorithm-driven, guideline-based medication initiation/titration, and laboratory testing until patients achieved LDL-C goals or exited the program. As a clinical effectiveness program for cholesterol guideline implementation, comparison was made to those contacted patients who declined program-based medication management, and received education only, along with their usual care. RESULTS: 1021 patients falling into guideline-defined high ASCVD risk groups warranting statin therapy (ASCVD, type 2 diabetes, LDL ≥ 190 mg/dL, calculated 10-year ASCVD risk ≥7.5%) and not achieving guideline-defined target LDL-C levels and/or therapy were identified and contacted. Among the 698 such patients who opted for program medication management, significant LDL-C reductions occurred in the total cohort (mean -65.4 mg/dL, 45% decrease), and each high ASCVD risk subgroup: ASCVD (-57.2 mg/dL, -48.0%); diabetes mellitus (-53.1 mg/dL, -40.0%); severe hypercholesterolemia (-76.3 mg/dL, -45.7%); elevated ASCVD 10-year risk (-62.8 mg/dL, -41.1%) (P<0.001 for all), without any significant complications. Among 20% of participants with reported statin intolerance, average LDL-C decreased from baseline 143 mg/dL to 85 mg/dL using mainly statins and ezetimibe, with limited PCSK9 inhibitor use. In comparison, eligible high ASCVD risk patients who were contacted but opted for education only, a 17% LDL-C decrease occurred over a similar timeframe, with 80% remaining with an LDL-C over 100 mg/dL. CONCLUSIONS: A remote, algorithm-driven, navigator-executed cholesterol management program successfully identified high ASCVD risk undertreated patients using EMR screening and was associated with significantly improved guideline-directed LDL-C control, supporting this approach as a novel strategy for improving health care access and delivery.

A Review on Coupled Bulk Acoustic Wave MEMS Resonators.

With the introduction of the working principle of coupled resonators, the coupled bulk acoustic wave (BAW) Micro-Electro-Mechanical System (MEMS) resonators have been attracting much attention. In this paper, coupled BAW MEMS resonators are discussed, including the coupling theory, the actuation and sensing theory, the transduction mechanism, and the applications. BAW MEMS resonators normally exhibit two types of vibration modes: lateral (in-plane) modes and flexural (out-of-plane) modes. Compared to flexural modes, lateral modes exhibit a higher stiffness with a higher operating frequency, resulting in a lower internal loss. Also, the lateral mode has a higher Q factor, as the fluid damping imposes less influence on the in-plane motion. The coupled BAW MEMS resonators in these two vibration modes are investigated in this work and their applications for sensing, timing, and frequency reference are also presented.

Generation of tailored terahertz waves from monolithic integrated metamaterials onto spintronic terahertz emitters.

Recently emerging spintronic terahertz (THz) emitters, featuring many appreciable merits such as low-cost, high efficiency, ultrabroadband, and ease of integration, offer multifaceted capabilities not only in understanding the fundamental ultrafast magnetism physics but also for exploring multifarious practical applications. Integration of various flexible and tunable functions at the source such as polarization manipulation, amplitude tailoring, phase modulation, and radiation beam steering with the spintronic THz emitters and their derivatives can yield more compact and elegant devices. Here, we demonstrate a monolithic metamaterial integrated onto a W/CoFeB/Pt THz nanoemitter for a purpose-designed functionality of the electromagnetically induced transparency analog. Through elaborate engineering the asymmetry degree and geometric parameters of the metamaterial structure, we successfully verified the feasibility of monolithic modulations for the radiated THz waves. The integrated device was eventually compared with a set of stand-alone metamaterial positioning scenarios, and the negligible frequency difference between two of the positioning schemes further manifests almost an ideal realization of the proposed monolithic integrated metamaterial device with a spintronic THz emitter. We believe that such adaptable and scalable devices may make valuable contributions to the designable spintronic THz devices with pre-shaping THz waves and enable chip-scale spintronic THz optics, sensing, and imaging.

Monitoring Lower Back Activity in Daily Life Using Small Unintrusive Sensors and Wearable Electronics in the Context of Rheumatic and Musculoskeletal Diseases.

Due to a sedentary lifestyle, the amount of people suffering from musculoskeletal back diseases has increased over the last few decades. To monitor and cure these disabilities, sensors able to monitor the patient for long-term measurement during daily life and able to provide real-time feedback are required. There are only a few wearable systems that are capable to acquire muscle activity (sEMG) and posture at the same time. Moreover, previously reported systems do not target back sensor and typically comprise bulky uncomfortable solutions. In this paper, we present a new wearable sensor network that is designed to measure muscle activity and posture specialized for back measurement. Special care was taken to propose a discrete and comfortable solution. The prototype only measures 3.1 mm in thickness on the spine, making this sensor system the thinnest and lightest one in the literature to our best knowledge. After testing, it was shown that the sensor system is able to acquire two surface electromyography signals concurrently, to gather acceleration and rotation speed from the patient's lower back, and to transmit data to a computer or a smartphone via serial communication or Bluetooth low energy for a few hours for later processing and analysis.

Micromachined Accelerometers with Sub-µg/√Hz Noise Floor: A Review.

This paper reviews the research and development of micromachined accelerometers with a noise floor lower than 1 µg/√Hz. Firstly, the basic working principle of micromachined accelerometers is introduced. Then, different methods of reducing the noise floor of micromachined accelerometers are analyzed. Different types of micromachined accelerometers with a noise floor below 1 µg/√Hz are discussed. Such sensors can mainly be categorized into: (i) micromachined accelerometers with a low spring constant; (ii) with a large proof mass; (iii) with a high quality factor; (iv) with a low noise interface circuit; (v) with sensing schemes leading to a high scale factor. Finally, the characteristics of various micromachined accelerometers and their trends are discussed and investigated.

Resonating Shell: A Spherical-Omnidirectional Ultrasound Transducer for Underwater Sensor Networks.

This paper presents the design and fabrication process of a spherical-omnidirectional ultrasound transducer for underwater sensor network applications. The transducer is based on the vibration of two hemispheres with a thickness of 1 mm and an outer diameter of 10 mm, which are actuated by two piezoelectric ring elements. Since the ultrasound wave is generated by the vibration of the two hemispheres, a matching layer is not required. Silicon Carbide (SiC) is used as the material of the hemispherical shells of the transducer. The shells were fabricated by laser sintering as an additive manufacturing method, in which the hemispheres were built layer by layer from a powder bed. All manufactured transducers with an outer dimension of 10 × 14.2 mm and a center frequency of 155 kHz were measured in a water tank by a hydrophone or in mutual communication. The circumferential source level was measured to vary less than 5dB. The power consumption and the insertion loss of the transducer, ranging from 100 µ W to 2.4 mW and 21.2 dB, respectively, along with all other measurements, prove that the transducer can transmit and receive ultrasound waves omnidirectionally at tens of centimeters intervals with a decent power consumption and low actuation voltage.

Magnetic Cell Centrifuge Platform Performance Study with Different Microsieve Pore Geometries.

The detection and analysis of circulating tumor cells (CTCs) plays a crucial role in clinical practice. However, the heterogeneity and rarity of CTCs make their capture and separation from peripheral blood very difficult while maintaining their structural integrity and viability. We previously demonstrated the effectiveness of the Magnetic Cell Centrifuge Platform (MCCP), which combined the magnetic-labeling cell separation mechanism with the size-based method. In this paper, a comparison of the effectiveness of different microsieve pore geometries toward MCCP is demonstrated to improve the yield of the target cell capture. Firstly, models of a trapped cell with rectangular and circular pore geometries are presented to compare the contact force using finite element numerical simulations. The device performance is then evaluated with both constant pressure and constant flow rate experimental conditions. In addition, the efficient isolation of magnetically labeled Hela cells with red fluorescent proteins (target cells) from Hela cells with green fluorescent protein (background cells) is validated. The experimental results show that the circular sieves yield 97% purity of the target cells from the sample with a throughput of up to 2 µL/s and 66-fold sample enrichment. This finding will pave the way for the design of a higher efficient MCCP systems.

Spider Chitin: An Ultrafast Microwave-Assisted Method for Chitin Isolation from Caribena versicolor Spider Molt Cuticle.

Chitin, as a fundamental polysaccharide in invertebrate skeletons, continues to be actively investigated, especially with respect to new sources and the development of effective methods for its extraction. Recent attention has been focused on marine crustaceans and sponges; however, the potential of spiders (order Araneae) as an alternative source of tubular chitin has been overlooked. In this work, we focused our attention on chitin from up to 12 cm-large Theraphosidae spiders, popularly known as tarantulas or bird-eating spiders. These organisms "lose" large quantities of cuticles during their molting cycle. Here, we present for the first time a highly effective method for the isolation of chitin from Caribena versicolor spider molt cuticle, as well as its identification and characterization using modern analytical methods. We suggest that the tube-like molt cuticle of this spider can serve as a naturally prefabricated and renewable source of tubular chitin with high potential for application in technology and biomedicine.

Significant Published Articles for Pharmacy Nutrition Support Practice in 2014 and 2015.

PURPOSE: To assist the pharmacy clinician engaged in nutrition support in staying current with the most pertinent literature. METHODS: Several experienced board-certified clinical pharmacists engaged in nutrition support therapy compiled a list of articles published in 2014 and 2015 that they considered to be important to their practice. Only those articles available in print format were considered for potential inclusion. Articles available only in preprint electronic format were not evaluated. The citation list was compiled into a single spreadsheet where the author participants were asked to ascertain whether they considered the paper important to nutrition support pharmacy practice. A culled list of publications was then identified whereby the majority of author participants (at least 5 out of 8) considered the paper to be important. RESULTS: A total of 108 articles were identified; 36 of which were considered to be of high importance. An important guideline article published in early 2016, but not ranked, was also included. The top-ranked articles from the primary literature were reviewed. CONCLUSION: It is recommended that the informed pharmacist, who is engaged in nutrition support therapy, be familiar with the majority of these articles.

Efficacy of a Creon delayed-release pancreatic enzyme protocol for clearing occluded enteral feeding tubes.

BACKGROUND: Alkalinized Viokase pancreatic enzyme tablets restored patency to 71.9% of occluded Dobhoff tubes in a prospective study. After removal of Viokase tablets from the US market, the hospital protocol for unclogging enteral feeding tubes was adapted to use Creon pancreatic enzyme delayed-release capsules, despite the lack of published data. OBJECTIVE: To evaluate the effectiveness of a Creon-based protocol to clear occluded enteral feeding tubes. METHODS: This retrospective study included all adult and pediatric patients seen in the emergency department or in an inpatient setting who received Creon 12 000 units lipase delayed-release capsule dissolved in a solution of sodium bicarbonate 650 mg and sterile water for clearing occluded enteral feeding tubes between May 1 and November 30, 2010. The Creon protocol was deemed effective if tube clearance was documented in the medical record or if enteral feedings were resumed with no note regarding tube replacement. RESULTS: Alkalinized Creon delayed-release capsules were administered to 83 patients with a total of 118 clogged tubes. Three poorly documented cases and 5 tubes with mechanical clogs were excluded from data analysis. Patency was restored to 53 of 110 (48.2%) occluded tubes. More than 1 treatment course was attempted in 5 cases, with success in 3. CONCLUSION: An alkalinized Creon pancreatic enzyme protocol was effective in clearing approximately half of the occluded enteral feeding tubes in this retrospective study, an efficacy rate much less than that previously reported in the literature with a Viokase-based protocol.

Significant publications for pharmacy nutrition support practice in 2013.

PURPOSE: To assist the pharmacy clinician engaged in nutrition support in staying current with the most pertinent literature. METHODS: Several experienced board-certified clinical pharmacists in nutrition support compiled a list of publications published in 2013 that they considered to be important to their practice. The citation list was compiled into a Web-based survey whereby pharmacist members of the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.), GI-Liver-Nutrition Practice Research Network of the American College of Clinical Pharmacy, and the Pharmacy and Pharmacology Section of the Society of Critical Care Medicine were asked to rank each article according to level of importance in their practice. RESULTS: A total of 30 articles were identified by the author group. Thirty-six participants responded to the survey. The top-ranked papers by participants from the Web-based survey were reviewed by the authors. Due to its high level of importance, the parenteral nutrition safety consensus recommendations article, to be published in 2014 by A.S.P.E.N., was also reviewed. CONCLUSION: It is recommended that the informed pharmacist, who is engaged in nutrition support therapy, be familiar with the majority of these publications.

Near-zero stiffness accelerometer with buckling of tunable electrothermal microbeams.

Pre-shaped microbeams, curved or inclined, are widely used in MEMS for their interesting stiffness properties. These mechanisms allow a wide range of positive and negative stiffness tuning in their direction of motion. A mechanism of pre-shaped beams with opposite curvature, connected in a parallel configuration, can be electrothermally tuned to reach a near-zero or negative stiffness behavior at the as-fabricated position. The simple structure helps incorporate the tunable spring mechanism in different designs for accelerometers, even with different transduction technologies. The sensitivity of the accelerometer can be considerably increased or tuned for different applications by electrothermally changing the stiffness of the spring mechanism. Opposite inclined beams are implemented in a capacitive micromachined accelerometer. The measurements on fabricated prototypes showed more than 55 times gain in sensitivity compared to their initial sensitivity. The experiments showed promising results in enhancing the resolution of acceleration sensing and the potential to reach unprecedent performance in micromachined accelerometers.

Understanding paraneoplastic syndromes in athletes.

The understanding of paraneoplastic syndromes has improved over the last several years. These disorders are brought about by tumor secretion of substances that can alter hormonal function and create immune cross-reactivity with normal tissues. This, in turn, can alter normal metabolic pathways resulting in paraneoplastic syndromes. The athlete must maintain an awareness of their body because these syndromes affect diverse organ systems. Commonly associated malignancies include small cell lung cancer, breast cancer, gynecologic tumors, and gastroenterological malignancies. These cancers most notably affect the neuromuscular, rheumatologic, mucocutaneous, hematologic, renal, and endocrine systems. Effective diagnosis and treatment of paraneoplastic syndromes most often require appropriate diagnosis and treatment of the underlying malignancy. This review focuses on the most commonly encountered paraneoplastic syndromes, so athletes and those who care for them can be aware of the potential risk of an occult or recurrent malignancy.

Full-electric microfluidic platform to capture, analyze and selectively release single cells.

Current single-cell technologies require large and expensive equipment, limiting their use to specialized labs. In this paper, we present for the first time a microfluidic device which demonstrates a combined method for full-electric cell capturing, analyzing, and selectively releasing with single-cell resolution. All functionalities are experimentally demonstrated on Saccharomyces cerevisiae. Our microfluidic platform consists of traps centered around a pair of individually accessible coplanar electrodes, positioned under a microfluidic channel. Using this device, we validate our novel Two-Voltage method for trapping single cells by positive dielectrophoresis (pDEP). Cells are attracted to the trap when a high voltage (VH) is applied. A low voltage (VL) holds the already trapped cell in place without attracting additional cells, allowing full control over the number of trapped cells. After trapping, the cells are analyzed by broadband electrochemical impedance spectroscopy. These measurements allow the detection of single cells and the extraction of cell parameters. Additionally, these measurements show a strong correlation between average phase change and cell size, enabling the use of our system for size measurements in biological applications. Finally, our device allows selectively releasing trapped cells by turning off the pDEP signal in their trap. The experimental results show the techniques potential as a full-electric single-cell analysis tool with potential for miniaturization and automation which opens new avenues towards small-scale, high throughput single-cell analysis and sorting lab-on-CMOS devices.

Development of complexity categories for an investigational drug services complexity scoring tool to assess pharmacy effort in clinical trial initiation and maintenance.

PURPOSE: Research pharmacy effort required to safely and compliantly manage investigational products (IP) varies between studies. No validated tool exists in the United States to evaluate these differences in effort. The Vizient Pharmacy Research Committee Investigational Drug Services (IDS) Subcommittee previously developed a systematic complexity scoring tool (CST) through expert consensus to assign a complexity score for pharmacy effort. This project seeks to develop and validate complexity categories based on CST scores. METHODS: Vizient member institutions in IDS assigned a CST complexity score and a perceived complexity category (low, medium, or high) for study initiation and maintenance. Receiver operating characteristic (ROC) curve analysis defined the best CST score cutoff points for each complexity category. Comparing the CST-assigned to the user-perceived complexity category determined whether the CST-assigned complexity category aligned with practitioner assignment. RESULTS: A total of 322 responses were used to determine complexity score categories. The AUC values for study initiation and maintenance were 0.79 (P < 0.001) for the low/medium boundary and 0.80 (P < 0.001) for the medium/high boundary, suggesting the performance of the CST is good. The agreement between CST-assigned and user-perceived complexity categories was 60% for study initiation and 58% for maintenance. The Kendall rank correlation coefficient between the raters and ROC categories was strong, with a value of 0.48 for study initiation and 0.47 for maintenance. CONCLUSION: Development of the CST allows IDS pharmacies to objectively measure the complexity of clinical trials, which is a significant step towards assessing workload and guiding resource allocation.

Opportunities in optical and electrical single-cell technologies to study microbial ecosystems.

New techniques are revolutionizing single-cell research, allowing us to study microbes at unprecedented scales and in unparalleled depth. This review highlights the state-of-the-art technologies in single-cell analysis in microbial ecology applications, with particular attention to both optical tools, i.e., specialized use of flow cytometry and Raman spectroscopy and emerging electrical techniques. The objectives of this review include showcasing the diversity of single-cell optical approaches for studying microbiological phenomena, highlighting successful applications in understanding microbial systems, discussing emerging techniques, and encouraging the combination of established and novel approaches to address research questions. The review aims to answer key questions such as how single-cell approaches have advanced our understanding of individual and interacting cells, how they have been used to study uncultured microbes, which new analysis tools will become widespread, and how they contribute to our knowledge of ecological interactions.

Micrographic View of Graft Union Formation Between Watermelon Scion and Squash Rootstock.

Grafting has become a common practice for watermelon [Citrullus lanatus (Thunb.) Matsum & Nakai] production in many parts of the world, due to its efficacy against biotic and abiotic stressors. However, grafting success for watermelon is challenging in part due to the complex anatomy of the cucurbit vascular system. The survival of grafted transplants depends on compatibility between the scion and rootstock, which in turn depends on anatomical, physiological, and genetic variables. A better understanding of cucurbit anatomy and graft union formation would inform grafting approaches and transplant management. An anatomical study was conducted by scanning electron microscopy (SEM) at 11 and 25 days after grafting (DAG) with seedless watermelon cultivar 'Secretariat' grafted onto compatible rootstock cultivars 'Pelop' (Lagenaria siceraria) and 'Tetsukabuto' (Cucurbita maxima × Cucurbita moschata) in comparison to non-grafted watermelon and rootstock seedlings. At 11 DAG, the parenchymatic cells of the central pith of grafted plants were dead and a necrotic layer was observed, representing the beginning of callus formation. New xylem strands were formed in the vascular system, connecting the rootstock with the scion. At 25 DAG, fully developed vascular bundles at the graft interface were observed with both scion-rootstock combinations. Although more studies are necessary to characterize the sequence of physiological events after grafting in Cucurbit species, this is one of the first studies to describe the complex anatomical changes that occur during watermelon graft healing.

Thin flexible arrays for long-term multi-electrode recordings in macaque primary visual cortex.

Objective.Basic, translational and clinical neuroscience are increasingly focusing on large-scale invasive recordings of neuronal activity. However, in large animals such as nonhuman primates and humans-in which the larger brain size with sulci and gyri imposes additional challenges compared to rodents, there is a huge unmet need to record from hundreds of neurons simultaneously anywhere in the brain for long periods of time. Here, we tested the electrical and mechanical properties of thin, flexible multi-electrode arrays (MEAs) inserted into the primary visual cortex of two macaque monkeys, and assessed their magnetic resonance imaging (MRI) compatibility and their capacity to record extracellular activity over a period of 1 year.Approach.To allow insertion of the floating arrays into the visual cortex, the 20 by 100µm2shafts were temporarily strengthened by means of a resorbable poly(lactic-co-glycolic acid) coating.Main results. After manual insertion of the arrays, theex vivoandin vivoMRI compatibility of the arrays proved to be excellent. We recorded clear single-unit activity from up to 50% of the electrodes, and multi-unit activity (MUA) on 60%-100% of the electrodes, which allowed detailed measurements of the receptive fields and the orientation selectivity of the neurons. Even 1 year after insertion, we obtained significant MUA responses on 70%-100% of the electrodes, while the receptive fields remained remarkably stable over the entire recording period.Significance.Thus, the thin and flexible MEAs we tested offer several crucial advantages compared to existing arrays, most notably in terms of brain tissue compliance, scalability, and brain coverage. Future brain-machine interface applications in humans may strongly benefit from this new generation of chronically implanted MEAs.

Design of a large-range rotary microgripper with freeform geometries using a genetic algorithm.

This paper describes a novel electrostatically actuated microgripper with freeform geometries designed by a genetic algorithm. This new semiautomated design methodology is capable of designing near-optimal MEMS devices that are robust to fabrication tolerances. The use of freeform geometries designed by a genetic algorithm significantly improves the performance of the microgripper. An experiment shows that the designed microgripper has a large displacement (91.5 µm) with a low actuation voltage (47.5 V), which agrees well with the theory. The microgripper has a large actuation displacement and can handle micro-objects with a size from 10 to 100 µm. A grasping experiment on human hair with a diameter of 77 µm was performed to prove the functionality of the gripper. The result confirmed the superior performance of the new design methodology enabling freeform geometries. This design method can also be extended to the design of many other MEMS devices.