An energy-efficient wireless data link for implantable electronics

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2009.Cataloged from PDF version of thesis.Includes bibliographical references (p. 101-103).Low-power wireless links are important for the development of long-term implantable neural prostheses. Furthermore, in implanted systems with many neural recording electrodes, the data rate of the wireless link will need to be quite high since each recording electrode can produce about 120 kbps of data. For low-power operation, inductively-coupled near-field wireless links have shown great promise and were used to develop a power-efficient data link for biomedical implants. A prototype bi-directional, half-duplex wireless link based on inductive coupling was designed in a 0.18 [mu]m process. The uplink (i.e. data transmission from the internal transceiver) was designed to use an impedance modulation strategy. Since this technique only requires a single local oscillator (LO) in the external transceiver, the energy expenditure of the implanted transceiver is minimized. Simulated uplink data transfer rates of up to 10 Mbps has been shown. A PWM based ASK coding strategy was used for the downlink (i.e. data transmission to the implanted device). The downlink is able to achieve a data transfer rate of up to 1.5 Mbps. A technique to reduce BER of inductive coupling links due to pulse-width distortion effects by pre-distorting the transmitted data is also presented. A calibration technique to reduce the resonant frequency mismatch between the two magnetically coupled resonators is also shown.by Daniel Prashanth Kumar.S.M

Genomic landscape of clinically advanced KRAS wild-type pancreatic ductal adenocarcinoma

IntroductionKRAS mutation is a common occurrence in Pancreatic Ductal Adenocarcinoma (PDA) and is a driver mutation for disease development and progression. KRAS wild-type PDA may constitute a distinct molecular and clinical subtype. We used the Foundation one data to analyze the difference in Genomic Alterations (GAs) that occur in KRAS mutated and wild-type PDA.MethodsComprehensive genomic profiling (CGP) data, tumor mutational burden (TMB), microsatellite instability (MSI) and PD-L1 by Immunohistochemistry (IHC) were analyzed.Results and discussionOur cohort had 9444 cases of advanced PDA. 8723 (92.37%) patients had KRAS mutation. 721 (7.63%) patients were KRAS wild-type. Among potentially targetable mutations, GAs more common in KRAS wild-type included ERBB2 (mutated vs wild-type: 1.7% vs 6.8%, p <0.0001), BRAF (mutated vs wild-type: 0.5% vs 17.9%, p <0.0001), PIK3CA (mutated vs wild-type: 2.3% vs 6.5%, p <0.001), FGFR2 (mutated vs wild-type: 0.1% vs 4.4%, p <0.0001), ATM (mutated vs wild-type: 3.6% vs 6.8%, p <0.0001). On analyzing untargetable GAs, the KRAS mutated group had a significantly higher percentage of TP53 (mutated vs wild-type: 80.2% vs 47.6%, p <0.0001), CDKN2A (mutated vs wild-type: 56.2% vs 34.4%, p <0.0001), CDKN2B (mutated vs wild-type: 28.9% vs 23%, p =0.007), SMAD4 (mutated vs wild-type: 26.8% vs 15.7%, p <0.0001) and MTAP (mutated vs wild-type: 21.7% vs 18%, p =0.02). ARID1A (mutated vs wild-type: 7.7% vs 13.6%, p <0.0001 and RB1(mutated vs wild-type: 2% vs 4%, p =0.01) were more prevalent in the wild-type subgroup. Mean TMB was higher in the KRAS wild-type subgroup (mutated vs wild-type: 2.3 vs 3.6, p <0.0001). High TMB, defined as TMB > 10 mut/mB (mutated vs wild-type: 1% vs 6.3%, p <0.0001) and very-high TMB, defined as TMB >20 mut/mB (mutated vs wild-type: 0.5% vs 2.4%, p <0.0001) favored the wild-type. PD-L1 high expression was similar between the 2 groups (mutated vs wild-type: 5.7% vs 6%,). GA associated with immune checkpoint inhibitors (ICPIs) response including PBRM1 (mutated vs wild-type: 0.7% vs 3.2%, p <0.0001) and MDM2 (mutated vs wild-type: 1.3% vs 4.4%, p <0.0001) were more likely to be seen in KRAS wild-type PDA

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Calibration of sampling clock skew in high-speed, high-resolution time-interleaved ADCs

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2015.Cataloged from PDF version of thesis.Includes bibliographical references (pages 157-160).There is an ever-increasing demand for high-resolution and high-resolution ADCs. In order to raise the sampling rates of ADCs in a power efficient manner, time-interleaving is an essential technique, whereby N ADC channels, each operating at a sampling frequency of fs, are used to achieve an effective conversion rate of N - fs. While time-interleaving enables higher conversion rates in a given technology, mismatch issues such as gain, offset, and sampling clock skew between channels degrade the overall time-interleaved ADC performance. Of these issues, sampling clock skew between channels is the biggest problem in high-speed and high-resolution, time-interleaved ADCs as errors due to sampling clock skew become more severe for higher input frequencies. There are a few sources of sampling clock skew between channels. Mismatches in the sampling clock path and logic delays are the most obvious ones. Input signal routing mismatch and RC mismatch of the input sampling circuits also cause sampling clock skew. In this thesis, we developed two new methods to mitigate the effects of sampling clock skew in time-interleaved ADCs. The first is the rapid consecutive sampling method, whereby each interleaved channel is implemented using two sub-channel ADCs. Two consecutive samples of the input are taken with a short time delay between them. This allows for a straight-forward linear interpolation between the consecutive samples in order to recover the de-skewed sample. The second method entails introducing a programmable delay in the input signal path, instead of delaying the sampling clock, in order to calibrate out sampling clock skew. The design and implementation of a proof-of-concept, time-interleaved ADC that implements the input signal delay method is detailed. Finally, measurement results to show the efficacy of the proposed method in mitigating the effects of sampling clock skew is also presented.by Daniel Kumar.Ph. D

Residual Energy Monitoring in WirelessSensor Networks

Since wireless sensor networks are energy constrained, introducing a method that facilitates the efficient use of the available energy in each node is a fundamental design issue. In this work, a mechanism to monitor the residual energy of sensor networks is proposed. The information about the residual energy of each sensor node in the network is saved in a special node called monitoring node. This information can be used as input to other applications to prolong the network lifetime. Each sensor node in the network uses the proposed prediction-based model to forecast its energy consumption rate. The model's performance is measured based on the number of energy packets sent to the monitoring node for various thresholds (prediction errors). The simulation results showed that reducing the threshold will produce more accurate projection of the residual energy of each node in the monitoring node. However, as the threshold is further decreased the number of energy packets sent to the monitoring node grows significantly. This incurs higher energy map construction cost on the network in terms of energy and bandwidth. The simulation results also showed the tradeoff between increasing the accuracy of the prediction model and reducing the cost of energy map construction

Molecular Targets in Salivary Gland Cancers: A Comprehensive Genomic Analysis of 118 Mucoepidermoid Carcinoma Tumors

Introduction: Salivary gland carcinomas (SGC) are histologically diverse cancers and next-generation sequencing (NGS) to identify key molecular targets is an important aspect in the management of advanced cases. Methods: DNA was extracted from paraffin embedded tissues of advanced SGC and comprehensive genomic profiling (CGP) was carried out to evaluate for base substitutions, short insertions, deletions, copy number changes, gene fusions and rearrangements. Tumor mutation burden (TMB) was calculated on approximately 1.25 Mb. Some 324 genes in the FoundationOne CDX panel were analyzed. Results: Mucoepidermoid carcinoma (MECa) mutations were assessed. CDKN2A and CDKN2B GA were common in mucoepidermoid carcinoma (MECa) (52.5 and 30.5%). PIK3CA was also common in MECa (16.9%). ERBB2 amplification/short variants (amp/SV) were found in MECa (5.9/0%). HRAS GA was common in MECa (14.4%) as well. Other targets, including BAP1, PTEN, and KRAS, were noted but had a low incidence. In terms of immunotherapy (IO)-predictive markers, TMB > 10 was more common in MECa (16.9%). PDL1 high was also seen in MECa (4.20%). Conclusion: SGC are rare tumors with no FDA-approved treatment options. This large dataset reveals many opportunities for IO and targeted therapy contributing to the continuously increased precision in the selection of treatment for these patients