Initial experience of intraoperative identification of parathyroid glands with elastic scattering spectroscopy

BACKGROUND: Postoperative hypoparathyroidism due to damage to the parathyroid glands during a thyroidectomy is a well-known surgical complication. The current gold standard intraoperative method for identifying parathyroid glands is surgical judgment; other methods are limited in both their sensitivity and convenience. There is a clear need for an objective diagnostic tool that is effective in its identification of the parathyroid glands and of their viability. We hypothesized that an intraoperative tool using Elastic Scattering Spectroscopy (ESS) has the potential to differentiate optical signatures of the parathyroid gland from surrounding tissues in real-time. METHODS: ESS optical signatures were collected intraoperatively from perfused parathyroid, thyroid, fat, muscle, and nerve tissue during thyroidectomy. The ESS data was collected using a portable, handheld, noninvasive, "cold" fiber optic probe able to detect spectra in a non-ionizing, broadband spectrum of light (320 to 920 nm). Five measurements were collected at each tissue site over a total of 1.2 seconds. Visual analysis of tissue was analyzed and compared to pathology, and spectral measurements attained with ESS. RESULTS: No complications resulted from the use of the ESS probe. Of the 10 parathyroid glands evaluated to be at risk in the study, the optical probe utilizing ESS was able to detect unique spectral features associated with the parathyroid gland. All 10 parathyroid glands are optically differentiable from surrounding tissues with ESS. CONCLUSIONS: Utilizing spectroscopy in the form of a hand-held probe is feasible for intraoperative differentiation between tissue types. Preliminary results of this spectral technique warrant further investigation. If successful, implementation of a portable ESS probe to identify the parathyroid tissue during endocrine surgical procedures could reduce surgical complications and improve patient safety

Mixed Use of Analytical Derivatives and Algorithmic Differentiation for NMPC of Robot Manipulators

International audienceIn the context of nonlinear model predictive control (NMPC) for robot manipulators, we address the problem of enabling the mixed and transparent use of algorithmic differentiation (AD) and efficient analytical derivatives of rigid-body dynamics (RBD) to decrease the solution time of the subjacent optimal control problem (OCP). Efficient functions for RBD and their analytical derivatives are made available to the numerical optimization framework CasADi by overloading the operators in the implementations made by the RBD library Pinocchio and adding a derivative-overloading feature to CasADi. A comparison between analytical derivatives and AD is made based on their influence on the solution time of the OCP, showing the benefits of using analytical derivatives for RBD in optimal control of robot manipulators

The Genetic Age: Who Owns the Genome?: A Symposium on Intellectual Property and the Human Genome, 2 J. Marshall Rev. Intell. Prop. L. 6 (2002)

A Symposium on Intellectual Property Co-Sponsored by The Woodrow Wilson Center. Featuring the remarks of Scott A. Brown, J.D.; Q. Todd Dickinson, J.D.; Stephen P.A. Fodor, Ph.D.; Justin Gillis; Hon. Lee H. Hamilton; Eric S. Lander, Ph.D.; and Pilar Ossorio, Ph.D., J.D

Harnessing peripheral DNA methylation differences in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to reveal novel biomarkers of disease

Background Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease impacting an estimated 44 million adults worldwide. The causal pathology of AD (accumulation of amyloid-beta and tau), precedes hallmark symptoms of dementia by more than a decade, necessitating development of early diagnostic markers of disease onset, particularly for new drugs that aim to modify disease processes. To evaluate differentially methylated positions (DMPs) as novel blood-based biomarkers of AD, we used a subset of 653 individuals with peripheral blood (PB) samples in the Alzheimer’s disease Neuroimaging Initiative (ADNI) consortium. The selected cohort of AD, mild cognitive impairment (MCI), and age-matched healthy controls (CN) all had imaging, genetics, transcriptomics, cerebrospinal protein markers, and comprehensive clinical records, providing a rich resource of concurrent multi-omics and phenotypic information on a well-phenotyped subset of ADNI participants. Results In this manuscript, we report cross-diagnosis differential peripheral DNA methylation in a cohort of AD, MCI, and age-matched CN individuals with longitudinal DNA methylation measurements. Epigenome-wide association studies (EWAS) were performed using a mixed model with repeated measures over time with a P value cutoff of 1 × 10−5 to test contrasts of pairwise differential peripheral methylation in AD vs CN, AD vs MCI, and MCI vs CN. The most highly significant differentially methylated loci also tracked with Mini Mental State Examination (MMSE) scores. Differentially methylated loci were enriched near brain and neurodegeneration-related genes (e.g., BDNF, BIN1, APOC1) validated using the genotype tissue expression project portal (GTex). Conclusions Our work shows that peripheral differential methylation between age-matched subjects with AD relative to healthy controls will provide opportunities to further investigate and validate differential methylation as a surrogate of disease. Given the inaccessibility of brain tissue, the PB-associated methylation marks may help identify the stage of disease and progression phenotype, information that would be central to bringing forward successful drugs for AD

Multi-tissue integrative analysis of personal epigenomes

Evaluating the impact of genetic variants on transcriptional regulation is a central goal in biological science that has been constrained by reliance on a single reference genome. To address this, we constructed phased, diploid genomes for four cadaveric donors (using long-read sequencing) and systematically charted noncoding regulatory elements and transcriptional activity across more than 25 tissues from these donors. Integrative analysis revealed over a million variants with allele-specific activity, coordinated, locus-scale allelic imbalances, and structural variants impacting proximal chromatin structure. We relate the personal genome analysis to the ENCODE encyclopedia, annotating allele- and tissue-specific elements that are strongly enriched for variants impacting expression and disease phenotypes. These experimental and statistical approaches, and the corresponding EN-TEx resource, provide a framework for personalized functional genomics