A Spatially Diverse 2TX-3RX Galvanic-Coupled Transdural Telemetry for Tether-Less Distributed Brain-Computer Interfaces.

A near-field galvanic coupled transdural telemetry ASICs for intracortical brain-computer interfaces is presented. The proposed design features a two channels transmitter and three channels receiver (2TX-3RX) topology, which introduces spatial diversity to effectively mitigate misalignments (both lateral and rotational) between the brain and the skull and recovers the path loss by 13 dB when the RX is in the worst-case blind spot. This spatial diversity also allows the presented telemetry to support the spatial division multiplexing required for a high-capacity multi-implant distributed network. It achieves a signal-to-interference ratio of 12 dB, even with the adjacent interference node placed only 8 mm away from the desired link. While consuming only 0.33 mW for each channel, the presented RX achieves a wide bandwidth of 360 MHz and a low input referred noise of 13.21 nV/√Hz. The presented telemetry achieves a 270 Mbps data rate with a BER<10-6 and an energy efficiency of 3.4 pJ/b and 3.7 pJ/b, respectively. The core footprint of the TX and RX modules is only 100 and 52 mm2, respectively, minimizing the invasiveness of the surgery. The proposed transdural telemetry system has been characterized ex-vivo with a 7-mm thick porcine tissue.

High Accuracy Localization for Miniature Ingestible Devices Using Mutual Inductance.

This article demonstrates an inductively coupled high-accuracy localization system for miniature ingestible devices. It utilizes an inductance double capacitances-series capacitance (LCC-S) compensation architecture that enables mutual inductance measurement at primary side that is positioned outside the human body and less constrained by power budget and size than the miniature ingestible. Depending on the secondary circuit architecture, only limited and simple cooperative measurements are needed from the ingestible secondary side, which saves power and area in the miniature device. The errors in the system are modeled thoroughly, providing insights about system require-ments for a particular localization accuracy target for efficient design and to identify key building blocks with large influence on overall performance. The model shows that sub-centimeter localization root-mean-square error (RMSE) can be achieved with a modest external ADC (18bit) using three primary coils and three secondary coils. The localization is verified along a complete small intestine tract with realistic dimensions. The proposed model is verified by simulation and experiment showing that at the selected frequency range up to 5 MHz the body has no influence on the accuracy. The use of 0.9% saline as phantom is proposed which guarantees the analysis validity for all body types.

A SISO FMCW radar based on inherently frequency scanning antennas for 2-D indoor tracking of multiple subjects.

The contextual non-invasive monitoring and tracking of multiple human targets for health and surveillance purposes is an increasingly investigated application. Radars are good candidates, since they are able to remotely monitor people without raising privacy concerns. However, radar systems are typically based on complex architectures involving multiple channels and antennas, such as multiple-input and multiple-output (MIMO) or electronic beam scanning, resulting also in a high power consumption. In contrast with existing technologies, this paper proposes a single-input and single-output (SISO) frequency-modulated continuous wave (FMCW) radar in combination with frequency scanning antennas for tracking multiple subjects in indoor environments. A data processing method is also presented for angular separation and clutter removal. The system was successfully tested in five realistic indoor scenarios involving paired subjects, which were either static or moving along predefined paths varying their range and angular position. In all scenarios, the radar was able to track the targets, reporting a maximum mean absolute error (MAE) of 20 cm and 5.64[Formula: see text] in range and angle, respectively. Practical applications arise for ambient assisted living, telemedicine, smart building applications and surveillance.

Galvanic-coupled Trans-dural Data Transfer for High-bandwidth Intra-cortical Neural Sensing.

A digital-impulse galvanic coupling as a new high-speed trans-dural (from cortex to the skull) data transmission method has been presented in this paper. The proposed wireless telemetry replaces the tethered wires connected in between implants on the cortex and above the skull, allowing the brain implant to be "free-floating" for minimizing brain tissue damage. Such trans-dural wireless telemetry must have a wide channel bandwidth for high-speed data transfer and a small form factor for minimum invasiveness. To investigate the propagation property of the channel, a finite element model is developed and a channel characterization based on a liquid phantom and porcine tissue is performed. The results show that the trans-dural channel has a wide frequency response of up to 250 MHz. Propagation loss due to micro-motion and misalignments is also investigated in this work. The result indicates that the proposed transmission method is relatively insensitive to misalignment. It has approximately 1 dB extra loss when there is a horizontal misalignment of 1mm. A pulse-based transmitter ASIC and a miniature PCB module are designed and validated ex-vivo with a 10-mm thick porcine tissue. This work demonstrates a high-speed and miniature in-body galvanic-coupled pulse-based communication with a data rate up to 250 Mbps with an energy efficiency of 2 pJ/bit, and has a small module area of only 26 mm2.

Analytical Optimal Load Calculation of RF Energy Rectifiers Based on a Simplified Rectifying Model.

Wireless power transfer (WPT) is an essential enabler for novel sensor networks such as the wireless powered communication network (WPCN). The efficiency of an energy rectifier is dependent on both input power and loading condition. In this work, to maximize the rectifier efficiency, we present a low-complexity numerical method based on an analytical rectifier model to calculate the optimal load for different rectifier topologies, including half-wave and voltage-multipliers, without needing time-consuming simulations. The method is based on a simplified analytical rectifier model based on the diode equivalent circuit including parasitic parameters. Furthermore, by using Lambert-W function and the perturbation method, closed-form solutions are given for low-input power cases. The method is validated by means of both simulations and measurements. Extensive transient simulation results using different diodes (Skyworks SMS7630 and Avago HSMS285x) and frequency bands (400 MHz, 900 MHz, and 2.4 GHz) are provided for validation of the method. A 400 MHz 1- and 2-stage voltage multiplier are designed and fabricated, and measurements are conducted. Different input signals are used when validating the proposed methods, including the single sinewave signal and the multisine signal. The proposed numerical method shows excellent accuracy with both signal types, as long as the output voltage ripple is sufficiently low.

[Pyoderma gangrenosum: a complication following surgery for carpal tunnel syndrome]. / Pyoderma gangrenosum.

BACKGROUND: Pyoderma gangrenosum is a rare condition with an unpredictable disease course. The condition is accompanied by tissue decay and recognition often comes late. Pyoderma gangrenosum has clinical features similar to an infection, but does not react to antibiotics. The condition can develop following a surgical procedure or can be worsened by one. To date, only one other case of pyoderma gangrenosum following surgery for carpal tunnel syndrome has been described in the literature. CASE DESCRIPTION: A 60-year-old man developed painful ulcers shortly after surgery for carpal tunnel syndrome, a clinical picture representing a serious infection. Antibiotics and surgical debridement did not lead to improvement. Cultures from the wound did not contain micro-organisms. Following histological investigation a diagnosis of pyoderma gangrenosum was made. Administration of a high dosage of prednisone led to a swift improvement and the wound healed. CONCLUSION: Timely recognition of pyoderma gangrenosum is essential to prevent unnecessary surgical treatment and worsening of the condition. Systemic glucocorticoids are the treatment of first choice for pyoderma gangrenosum.

Meta-Analysis of Genome-Wide Association Studies and Network Analysis-Based Integration with Gene Expression Data Identify New Suggestive Loci and Unravel a Wnt-Centric Network Associated with Dupuytren's Disease.

Dupuytren´s disease, a fibromatosis of the connective tissue in the palm, is a common complex disease with a strong genetic component. Up to date nine genetic loci have been found to be associated with the disease. Six of these loci contain genes that code for Wnt signalling proteins. In spite of this striking first insight into the genetic factors in Dupuytren´s disease, much of the inherited risk in Dupuytren´s disease still needs to be discovered. The already identified loci jointly explain ~1% of the heritability in this disease. To further elucidate the genetic basis of Dupuytren´s disease, we performed a genome-wide meta-analysis combining three genome-wide association study (GWAS) data sets, comprising 1,580 cases and 4,480 controls. We corroborated all nine previously identified loci, six of these with genome-wide significance (p-value < 5x10-8). In addition, we identified 14 new suggestive loci (p-value < 10-5). Intriguingly, several of these new loci contain genes associated with Wnt signalling and therefore represent excellent candidates for replication. Next, we compared whole-transcriptome data between patient- and control-derived tissue samples and found the Wnt/ß-catenin pathway to be the top deregulated pathway in patient samples. We then conducted network and pathway analyses in order to identify protein networks that are enriched for genes highlighted in the GWAS meta-analysis and expression data sets. We found further evidence that the Wnt signalling pathways in conjunction with other pathways may play a critical role in Dupuytren´s disease.

Dupuytren diathesis and genetic risk.

PURPOSE: Dupuytren disease (DD) is a benign fibrosing disorder of the hand and fingers. Recently, we identified 9 single nucleotide polymorphisms (SNPs) associated with DD in a genome-wide association study. These SNPs can be used to calculate a genetic risk score for DD. The aim of this study was to test whether certain clinical characteristics (including the DD diathesis features) of patients with DD are associated with a high genetic risk score. METHODS: Between 2007 and 2010, we prospectively invited all DD patients (1,120 in total) to participate. Clinical characteristics were noted using patient- and doctor-completed questionnaires, and blood was obtained for DNA analysis. We analyzed a total of 933 subjects with genetic and clinical data. The 9 previously identified DD SNPs were used to calculate a weighted genetic risk score. Patients were categorized into high and low genetic risk score groups, according to their weighted genetic risk score. Logistic regression was performed to study the association of clinical characteristics with a high genetic risk score. RESULTS: In a univariate regression model, patients with an age of onset of DD younger than 50 years, a family history positive for DD, knuckle pads, and Ledderhose disease were statistically significantly associated with a high genetic risk score. In an additional analysis using high and low genetic risk groups that deviate further from the median, Ledderhose disease was no longer significantly associated with DD. CONCLUSIONS: Patients with DD who present with these diathesis features, and predominantly patients with knuckle pads, are more likely to carry more risk alleles for the discovered DD SNPs than patients without these diathesis features. CLINICAL RELEVANCE: These markers may prove useful in predicting disease progression or recurrence.

WNT2 locus is involved in genetic susceptibility of Peyronie's disease.

INTRODUCTION: Peyronie's disease (PD) is a fibromatosis of the penis, with a pathology very similar to what is seen in the hand (palmar fascia) in Dupuytren's disease (DD). Recently, we performed a genome-wide association study and identified nine genetic loci containing common variants associated with DD. Seven of these loci mapped within or near genes of the canonical WNT pathway and each locus yielded relatively large odds ratios (ORs) for DD disease status. AIM: Given the clinical overlap between PD and DD, we examined whether the nine DD susceptibility loci are also involved in PD. METHODS: An association study was performed using a case/control design. From 2007 to 2010, we prospectively included 111 men who had been clinically diagnosed with PD. Control subjects (N = 490 males) were randomly drawn from a population-based cohort from the same region of the Netherlands. Allele frequencies in the 111 PD cases and 490 controls were compared using a 1-degree-of-freedom basic chi-square test. A P value < 0.05 after Bonferroni correction for the nine tested single nucleotide polymorphisms (SNPs) was considered statistically significant (i.e., P < 0.0056). MAIN OUTCOME MEASURE: Association of genetic markers (SNPs) with PD. RESULTS: We observed significant association with SNP rs4730775 at the wingless-type MMTV integration site family member 2 (WNT2) locus on chromosome 7 (P = 0.0015, OR 0.61), but found no evidence for the other eight loci being involved with PD despite the large effect size seen for some of these variants in DD. The WNT2 association was even more significant after we removed 15 patients with comorbid DD. CONCLUSIONS: WNT2 is a susceptibility locus for PD and our finding provides evidence for a partly shared genetic susceptibility between PD and DD.

Wnt signaling and Dupuytren's disease.

BACKGROUND: Dupuytren's disease is a benign fibromatosis of the hands and fingers that leads to flexion contractures. We hypothesized that multiple genetic and environmental factors influence susceptibility to this disease and sought to identify susceptibility genes to better understand its pathogenesis. METHODS: We conducted a genomewide association study of 960 Dutch persons with Dupuytren's disease and 3117 controls (the discovery set) to test for association between the disease and genetic markers. We tested the 35 single-nucleotide polymorphisms (SNPs) most strongly associated with Dupuytren's disease (P<1×10(-4)) in the discovery set in three additional, independent case series comprising a total of 1365 affected persons and 8445 controls from Germany, the United Kingdom, and The Netherlands. RESULTS: Initially, we observed a significant genomewide association between Dupuytren's disease and 8 SNPs at three loci. Tests of replication and joint analysis of all data from 2325 patients with Dupuytren's disease and 11,562 controls yielded an association with 11 SNPs from nine different loci (P<5.0×10(-8)). Six of these loci contain genes known to be involved in the Wnt-signaling pathway: WNT4 (rs7524102) (P=2.8×10(-9); odds ratio, 1.28), SFRP4 (rs16879765) (P=5.6×10(-39); odds ratio, 1.98), WNT2 (rs4730775) (P=3.0×10(-8); odds ratio, 0.83), RSPO2 (rs611744) (P=7.9×10(-15); odds ratio, 0.75), SULF1 (rs2912522) (P=2.0×10(-13); odds ratio, 0.72), and WNT7B (rs6519955) (P=3.2×10(-33); odds ratio, 1.54). CONCLUSIONS: This study implicates nine different loci involved in genetic susceptibility to Dupuytren's disease. The fact that six of these nine loci harbor genes encoding proteins in the Wnt-signaling pathway suggests that aberrations in this pathway are key to the process of fibromatosis in Dupuytren's disease.

A lightweight security scheme for wireless body area networks: design, energy evaluation and proposed microprocessor design.

In order for wireless body area networks to meet widespread adoption, a number of security implications must be explored to promote and maintain fundamental medical ethical principles and social expectations. As a result, integration of security functionality to sensor nodes is required. Integrating security functionality to a wireless sensor node increases the size of the stored software program in program memory, the required time that the sensor's microprocessor needs to process the data and the wireless network traffic which is exchanged among sensors. This security overhead has dominant impact on the energy dissipation which is strongly related to the lifetime of the sensor, a critical aspect in wireless sensor network (WSN) technology. Strict definition of the security functionality, complete hardware model (microprocessor and radio), WBAN topology and the structure of the medium access control (MAC) frame are required for an accurate estimation of the energy that security introduces into the WBAN. In this work, we define a lightweight security scheme for WBAN, we estimate the additional energy consumption that the security scheme introduces to WBAN based on commercial available off-the-shelf hardware components (microprocessor and radio), the network topology and the MAC frame. Furthermore, we propose a new microcontroller design in order to reduce the energy consumption of the system. Experimental results and comparisons with other works are given.

Giant fibroadenoma of one breast: Immediate bilateral reconstruction.

A rare case of giant fibroadenoma of the left breast is presented. We performed a nipple sparing subcutaneous mastectomy of the left breast. Since the patient desired larger breasts, a contralateral augmentation mammaplasty was carried out in a single stage operation. A satisfactory result was achieved.