The Evaluation and Treatment of Merkel Cell Carcinoma and Brain Metastasis: A Case Report and Review of the Literature.

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor associated with high mortality if metastases are identified. Currently, there is no standardized nor curative treatment for neurometastatic MCC. In this study, we have reviewed the more recent cases and the use of immunotherapy in a population. In this case report and review, we present a case of MCC with brain metastasis currently undergoing treatment with immunotherapy (pembrolizumab) resulting in an initial complete response with a progression-free survival time of five months. We also review the past reported literature and the 11 newly presented cases on their clinical presentation of neurometastatic MCC, immunohistochemical markers, and treatment outcomes. In summary, immunotherapy initially showed a promising response with the complete elimination of MCC brain metastasis. The early aggressive treatment of pembrolizumab with stereotactic radiosurgery should be considered as this treatment plan has shown improved therapeutic effects compared to the standard chemoradiation therapy. Further investigations are needed to determine the efficacy and response of immunotherapy use for neurometastatic MCC.

Novel Web-Based Music Re-Engineering Software for Enhancement of Music Enjoyment Among Cochlear Implantees.

OBJECTIVES: Cochlear implant (CI) listeners experience diminished music perception and enjoyment from a variety of patient-related and implant-related factors. We investigate the hypothesis that patient-directed music re-engineering may enhance music enjoyment with CI. STUDY DESIGN: Prospective cohort study. SETTING: Academic cochlear implant center. SUBJECTS AND METHODS: A multidisciplinary team of neurotologists, audiologists, and a sound/audio engineer collaborated with a web developer to create a music re-engineering application. Experienced adult CI listeners rated original excerpts from five major genres of music on enjoyment using a visual analog scale (VAS). Subjects were then allowed to re-engineer the original by adjusting treble frequencies, bass frequencies, percussion emphasis, and reverberation and again rated on enjoyment. RESULTS: Total of 46 subjects, with a mean age of 57.6 years (SD = 16; range, 18-90) participated in the study. User-mixed audio was rated higher across all measures of enjoyment than original recordings (mean difference +0.92; p < 0.05, CI [0.22, 1.62]), an effect that was seen across all genres except for country music. Subjects preferred louder bass frequencies (mean difference +7.1 dB; p < 0.01, CI [2.15, 24.3]) and more reverberation (mean difference +6.6 ms; p < 0.01, CI [2.85, 10.7]). Re-engineered music increased enjoyment in 57%, and 79% reported an interest in being able to mix music of their own choosing. CONCLUSION: User-directed music re-engineering increases music enjoyment for CI listeners. The cochlear implantee preferred heightened bass, reverberation, and treble across musical genres. These findings support the implementation of patient-directed music re-engineering to enhance music enjoyment with technology that is readily available today.

PARA: A one-meter reach, two-kg payload, three-DoF open source robotic arm with customizable end effector.

This article presents a robotic arm that is more cost effective than existing models on the market while still maintaining sufficient torque and speed capabilities. Most industrial-grade high power and precision arms are often very expensive, while conversely, more low-cost arms targeted toward the education and hobby sectors are inadequate in power and robustness. The Creative Machines Lab's three degree of freedom Printed Articulated Robotic Arm (PARA) can lift a 2 kg payload at a reach of 940 mm, while under a no-load case, it has exhibited a precision of about ±2.6 mm at an end effector speed of 250 mm/s. It costs about $3400 to build, an order of magnitude lower than market models with similar functionalities. This project is also meant to serve as a demonstration of the usage of 3D printed parts as practical tools in industry.

Negative Pressure Waves Based High Resolution Leakage Localization Method Using Piezoceramic Transducers and Multiple Temporal Convolutions.

The negative pressure wave (NPW) signals generated by a pipeline leakage often have a long signal duration. When these signals are utilized to compute the leakage position, the long signal duration will result in a large area being considered as leakage area. The localization resolution is low. A novel high-resolution localization algorithm is developed for pipeline leakage detection using piezoceramic transducers in this paper. The proposed algorithm utilizes multiple temporal convolutions to decrease the localization functional values at the points close to the leakage, in order to reduce the range of the leakage area revealed by the proposed algorithm. As a result, the localization resolution is improved. A measured experiment was conducted to study the proposed algorithm. In the experiment, the proposed algorithm was used to monitor a 55.8 m pressurized pipeline with two controllable valves and two Lead Zirconate Titanate (PZT) sensors. With the aid of the piezoceramic sensor, the experimental results show that the proposed algorithm results in a resolution which is better than that of the traditional method.

A Novel Embeddable Tubular Piezoceramics-Based Smart Aggregate for Damage Detection in Two-Dimensional Concrete Structures.

Due to their multiple advantages, piezoceramic materials have been widely used in structural health monitoring (SHM). Piezoceramic patch-based smart aggregate (SA) and spherical piezoceramic-based smart aggregate (SSA) have been developed for damage detection of concrete structures. However, the stress waves generated by these two types of transducers are limited by their geometry and are unsuitable for use in two-dimensional concrete structures (e.g., shear walls, floors and cement concrete pavements). In this paper, a novel embeddable tubular smart aggregate (TSA) based on a piezoceramic tube was designed, fabricated and tested for use in two-dimensional (2D) structures. Due to its special geometry, radially uniform stress waves can be generated, and thus the TSA is suitable for damage detection in planar structures. The suitability of the transducer for use in structural health monitoring was investigated by characterizing the ability of the transducer to transmit and measure stress waves. Three experiments, including impedance analysis, time of arrival analysis and sweep frequency analysis, were conducted to test the proposed TSA. The experimental results show that the proposed TSA is suitable for monitoring the health condition of two-dimensional concrete structures.

Design of a New Stress Wave-Based Pulse Position Modulation (PPM) Communication System with Piezoceramic Transducers.

Stress wave-based communication has great potential for succeeding in subsea environments where many conventional methods would otherwise face excessive difficulty, and it can benefit logging well by using the drill string as a conduit for stress wave propagation. To achieve stress wave communication, a new stress wave-based pulse position modulation (PPM) communication system is designed and implemented to transmit data through pipeline structures with the help of piezoceramic transducers. This system consists of both hardware and software components. The hardware is composed of a piezoceramic transducer that can generate powerful stress waves travelling along a pipeline, upon touching, and a PPM signal generator that drives the piezoceramic transducer. Once the transducer is in contact with a pipeline surface, the generator integrated with an amplifier is utilized to excite the piezoceramic transducer with a voltage signal that is modulated to encode the information. The resulting vibrations of the transducer generates stress waves that propagate throughout the pipeline. Meanwhile, piezoceramic sensors mounted on the pipeline convert the stress waves to electric signals and the signal can be demodulated. In order to enable the encoding and decoding of information in the stress wave, a PPM-based communication protocol was integrated into the software system. A verification experiment demonstrates the functionality of the developed system for stress wave communication using piezoceramic transducers and the result shows that the data transmission speed of this new communication system can reach 67 bits per second (bps).

A Review of Rock Bolt Monitoring Using Smart Sensors.

Rock bolts have been widely used as rock reinforcing members in underground coal mine roadways and tunnels. Failures of rock bolts occur as a result of overloading, corrosion, seismic burst and bad grouting, leading to catastrophic economic and personnel losses. Monitoring the health condition of the rock bolts plays an important role in ensuring the safe operation of underground mines. This work presents a brief introduction on the types of rock bolts followed by a comprehensive review of rock bolt monitoring using smart sensors. Smart sensors that are used to assess rock bolt integrity are reviewed to provide a firm perception of the application of smart sensors for enhanced performance and reliability of rock bolts. The most widely used smart sensors for rock bolt monitoring are the piezoelectric sensors and the fiber optic sensors. The methodologies and principles of these smart sensors are reviewed from the point of view of rock bolt integrity monitoring. The applications of smart sensors in monitoring the critical status of rock bolts, such as the axial force, corrosion occurrence, grout quality and resin delamination, are highlighted. In addition, several prototypes or commercially available smart rock bolt devices are also introduced.

Monitoring Concrete Deterioration Due to Reinforcement Corrosion by Integrating Acoustic Emission and FBG Strain Measurements.

Corrosion of concrete reinforcement members has been recognized as a predominant structural deterioration mechanism for steel reinforced concrete structures. Many corrosion detection techniques have been developed for reinforced concrete structures, but a dependable one is more than desired. Acoustic emission technique and fiber optic sensing have emerged as new tools in the field of structural health monitoring. In this paper, we present the results of an experimental investigation on corrosion monitoring of a steel reinforced mortar block through combined acoustic emission and fiber Bragg grating strain measurement. Constant current was applied to the mortar block in order to induce accelerated corrosion. The monitoring process has two aspects: corrosion initiation and crack propagation. Propagation of cracks can be captured through corresponding acoustic emission whereas the mortar expansion due to the generation of corrosion products will be monitored by fiber Bragg grating strain sensors. The results demonstrate that the acoustic emission sources comes from three different types, namely, evolution of hydrogen bubbles, generation of corrosion products and crack propagation. Their corresponding properties are also discussed. The results also show a good correlation between acoustic emission activity and expansive strain measured on the specimen surface.

Reduction of the Harmonic Series Influences Musical Enjoyment With Cochlear Implants.

OBJECTIVE: Cochlear implantation is associated with poor music perception and enjoyment. Reducing music complexity has been shown to enhance music enjoyment in cochlear implant (CI) recipients. In this study, we assess the impact of harmonic series reduction on music enjoyment. STUDY DESIGN: Prospective analysis of music enjoyment in normal-hearing (NH) individuals and CI recipients. SETTING: Single tertiary academic medical center. PATIENTS: NH adults (N = 20) and CI users (N = 8) rated the Happy Birthday song on three validated enjoyment modalities-musicality, pleasantness, and naturalness. INTERVENTION: Subjective rating of music excerpts. MAIN OUTCOME MEASURES: Participants listened to seven different instruments play the melody, each with five levels of harmonic reduction (Full, F3+F2+F1+F0, F2+F1+F0, F1+F0, F0). NH participants listened to the segments both with and without CI simulation. Linear mixed effect models (LME) and likelihood ratio tests were used to assess the impact of harmonic reduction on enjoyment. RESULTS: NH listeners without simulation rated segments with the first four harmonics (F3+F2+F1+F0) most pleasant and natural (p <0.001, p = 0.004). NH listeners with simulation rated the first harmonic alone (F0) most pleasant and natural (p <0.001, p = 0.003). Their ratings demonstrated a positive linear relationship between harmonic reduction and both pleasantness (slope estimate = 0.030, SE = 0.004, p <0.001, LME) and naturalness (slope estimate = 0.012, SE = 0.003, p = 0.003, LME). CI recipients also found the first harmonic alone (F0) to be most pleasant (p = 0.003), with a positive linear relationship between harmonic reduction and pleasantness (slope estimate = 0.029, SE = 0.008, p <0.001, LME). CONCLUSION: Harmonic series reduction increases music enjoyment in CI and NH individuals with or without CI simulation. Therefore, minimization of the harmonics may be a useful strategy for enhancing musical enjoyment among both NH and CI listeners.

FBG sensor for contact level monitoring and prediction of perforation in cardiac ablation.

Atrial fibrillation (AF) is the most common type of arrhythmia, and is characterized by a disordered contractile activity of the atria (top chambers of the heart). A popular treatment for AF is radiofrequency (RF) ablation. In about 2.4% of cardiac RF ablation procedures, the catheter is accidently pushed through the heart wall due to the application of excessive force. Despite the various capabilities of currently available technology, there has yet to be any data establishing how cardiac perforation can be reliably predicted. Thus, two new FBG based sensor prototypes were developed to monitor contact levels and predict perforation. Two live sheep were utilized during the study. It was observed during operation that peaks appeared in rhythm with the heart rate whenever firm contact was made between the sensor and the endocardial wall. The magnitude of these peaks varied with pressure applied by the operator. Lastly, transmural perforation of the left atrial wall was characterized by a visible loading phase and a rapid signal drop-off correlating to perforation. A possible pre-perforation signal was observed for the epoxy-based sensor in the form of a slight signal reversal (12-26% of loading phase magnitude) prior to perforation (occurring over 8 s).

A genome-wide analysis of small regulatory RNAs in the human pathogen group A Streptococcus.

The coordinated regulation of gene expression is essential for pathogens to infect and cause disease. A recently appreciated mechanism of regulation is that afforded by small regulatory RNA (sRNA) molecules. Here, we set out to assess the prevalence of sRNAs in the human bacterial pathogen group A Streptococcus (GAS). Genome-wide identification of candidate GAS sRNAs was performed through a tiling Affymetrix microarray approach and identified 40 candidate sRNAs within the M1T1 GAS strain MGAS2221. Together with a previous bioinformatic approach this brings the number of novel candidate sRNAs in GAS to 75, a number that approximates the number of GAS transcription factors. Transcripts were confirmed by Northern blot analysis for 16 of 32 candidate sRNAs tested, and the abundance of several of these sRNAs were shown to be temporally regulated. Six sRNAs were selected for further study and the promoter, transcriptional start site, and Rho-independent terminator identified for each. Significant variation was observed between the six sRNAs with respect to their stability during growth, and with respect to their inter- and/or intra-serotype-specific levels of abundance. To start to assess the contribution of sRNAs to gene regulation in M1T1 GAS we deleted the previously described sRNA PEL from four clinical isolates. Data from genome-wide expression microarray, quantitative RT-PCR, and Western blot analyses are consistent with PEL having no regulatory function in M1T1 GAS. The finding that candidate sRNA molecules are prevalent throughout the GAS genome provides significant impetus to the study of this fundamental gene-regulatory mechanism in an important human pathogen.

The youngest reported case of corticobasal degeneration.

Corticobasal degeneration (CBD) is a movement disorder characterized by early apraxia and asymmetric parkinsonism that responds poorly to anti-Parkinson medications. There are clinical manifestations reflecting dysfunction in both the cerebral cortex and the basal ganglia. Patients typically present between the sixth and seventh decades. Previously, the youngest clinically diagnosed individual was 40 years old. Here we describe a 34-year-old woman who meets the clinical diagnostic criteria for CBD with onset of symptoms at age 28. In this patient, the first symptom was an 'uncooperative' right hand. This was soon followed by right hand dystonia. Symptoms progressed rapidly, and she developed generalized bradykinesia, rigidity, and corticospinal tract signs with preservation of the initial asymmetry. Her symptoms did not respond to a daily dose of 1200 mg of immediate release levodopa. Extensive laboratory workup and brain imaging were normal. Neuropsychological evaluation revealed mild deficits consistent with frontal-subcortical dysfunction. The chronic, progressive course, asymmetric limb rigidity, apraxia, focal dystonia, and lack of response to levodopa suggest CBD. To our knowledge, this is the youngest reported case of clinically probable CBD.