Quantifying innovation in surgery

Objectives: The objectives of this study were to assess the applicability of patents and publications as metrics of surgical technology and innovation; evaluate the historical relationship between patents and publications; develop a methodology that can be used to determine the rate of innovation growth in any given health care technology. Background: The study of health care innovation represents an emerging academic field, yet it is limited by a lack of valid scientific methods for quantitative analysis. This article explores and cross-validates 2 innovation metrics using surgical technology as an exemplar. Methods: Electronic patenting databases and the MEDLINE database were searched between 1980 and 2010 for “surgeon” OR “surgical” OR “surgery.” Resulting patent codes were grouped into technology clusters. Growth curves were plotted for these technology clusters to establish the rate and characteristics of growth. Results: The initial search retrieved 52,046 patents and 1,801,075 publications. The top performing technology cluster of the last 30 years was minimally invasive surgery. Robotic surgery, surgical staplers, and image guidance were the most emergent technology clusters. When examining the growth curves for these clusters they were found to follow an S-shaped pattern of growth, with the emergent technologies lying on the exponential phases of their respective growth curves. In addition, publication and patent counts were closely correlated in areas of technology expansion. Conclusions: This article demonstrates the utility of publically available patent and publication data to quantify innovations within surgical technology and proposes a novel methodology for assessing and forecasting areas of technological innovation

Liver-specific activation of AMPK prevents steatosis on a high fructose diet

AMP-activated protein kinase (AMPK) plays a key role in integrating metabolic pathways in response to energy demand. We identified a mutation in the γ1 subunit (γ1D316A) that leads to activation of AMPK. We generated mice with this mutation to study the effect of chronic liver-specific activation of AMPK in vivo. Primary hepatocytes isolated from these mice have reduced gluconeogenesis and fatty acid synthesis, but there is no effect on fatty acid oxidation compared to cells from wild-type mice. Liver-specific activation of AMPK decreases lipogenesis in vivo and completely protects against hepatic steatosis when mice are fed a high-fructose diet. Our findings demonstrate that liver-specific activation of AMPK is sufficient to protect against hepatic triglyceride accumulation, a hallmark of non-alcoholic fatty liver disease (NAFLD). These results emphasize the clinical relevance of activating AMPK in the liver to combat NAFLD and potentially other associated complications (e.g., cirrhosis and hepatocellular carcinoma)

Escape rate and Hausdorff measure for entire functions

The escaping set of an entire function is the set of points that tend to infinity under iteration. We consider subsets of the escaping set defined in terms of escape rates and obtain upper and lower bounds for the Hausdorff measure of these sets with respect to certain gauge functions.Comment: 24 pages; some errors corrected, proof of Theorem 2 shortene

Electronic stress tensor analysis of hydrogenated palladium clusters

We study the chemical bonds of small palladium clusters Pd_n (n=2-9) saturated by hydrogen atoms using electronic stress tensor. Our calculation includes bond orders which are recently proposed based on the stress tensor. It is shown that our bond orders can classify the different types of chemical bonds in those clusters. In particular, we discuss Pd-H bonds associated with the H atoms with high coordination numbers and the difference of H-H bonds in the different Pd clusters from viewpoint of the electronic stress tensor. The notion of "pseudo-spindle structure" is proposed as the region between two atoms where the largest eigenvalue of the electronic stress tensor is negative and corresponding eigenvectors forming a pattern which connects them.Comment: 22 pages, 13 figures, published online, Theoretical Chemistry Account

A Close Nuclear Black Hole Pair in the Spiral Galaxy NGC 3393

The current picture of galaxy evolution advocates co-evolution of galaxies and their nuclear massive black holes (MBHs), through accretion and merging. Quasar pairs (6,000-300,000 light-years separation) exemplify the first stages of this gravitational interaction. The final stages, through binary MBHs and final collapse with gravitational wave emission, are consistent with the sub-light-year separation MBHs inferred from optical spectra and light-variability of two quasars. The double active nuclei of few nearby galaxies with disrupted morphology and intense star formation (e.g., NGC 6240 and Mkn 463; ~2,400 and ~12,000 light-years separation respectively) demonstrate the importance of major mergers of equal mass spirals in this evolution, leading to an elliptical galaxy, as in the case of the double radio nucleus (~15 light-years separation) elliptical 0402+379. Minor mergers of galaxies with a smaller companion should be a more common occurrence, evolving into spiral galaxies with active MBH pairs, but have hitherto not been seen. Here we report the presence of two active MBHs, separated by ~430 light-years, in the Seyfert galaxy NGC 3393. The regular spiral morphology and predominantly old circum-nuclear stellar population of this galaxy, and the closeness of the MBHs embedded in the bulge, suggest the result of minor merger evolution.Comment: Preprint (not final) version of a paper to appear in Natur

High-order chromatin architecture determines the landscape of chromosomal alterations in cancer

The rapid growth of cancer genome structural information provides an opportunity for a better understanding of the mutational mechanisms of genomic alterations in cancer and the forces of selection that act upon them. Here we test the evidence for two major forces, spatial chromosome structure and purifying (or negative) selection, that shape the landscape of somatic copy-number alterations (SCNAs) in cancer1. Using a maximum likelihood framework we compare SCNA maps and three-dimensional genome architecture as determined by genome-wide chromosome conformation capture (HiC) and described by the proposed fractal-globule (FG) model2. This analysis provides evidence that the distribution of chromosomal alterations in cancer is spatially related to three-dimensional genomic architecture and additionally suggests that purifying selection as well as positive selection shapes the landscape of SCNAs during somatic evolution of cancer cells

Evaluation of the zucker diabetic fatty (ZDF) rat as a model for human disease based on urinary peptidomic profiles

Representative animal models for diabetes-associated vascular complications are extremely relevant in assessing potential therapeutic drugs. While several rodent models for type 2 diabetes (T2D) are available, their relevance in recapitulating renal and cardiovascular features of diabetes in man is not entirely clear. Here we evaluate at the molecular level the similarity between Zucker diabetic fatty (ZDF) rats, as a model of T2D-associated vascular complications, and human disease by urinary proteome analysis. Urine analysis of ZDF rats at early and late stages of disease compared to age- matched LEAN rats identified 180 peptides as potentially associated with diabetes complications. Overlaps with human chronic kidney disease (CKD) and cardiovascular disease (CVD) biomarkers were observed, corresponding to proteins marking kidney damage (eg albumin, alpha-1 antitrypsin) or related to disease development (collagen). Concordance in regulation of these peptides in rats versus humans was more pronounced in the CVD compared to the CKD panels. In addition, disease-associated predicted protease activities in ZDF rats showed higher similarities to the predicted activities in human CVD. Based on urinary peptidomic analysis, the ZDF rat model displays similarity to human CVD but might not be the most appropriate model to display human CKD on a molecular level

Primary leiomyosarcoma of the right atrium: a case report and literature update

Leiomyosarcoma of the right atrium is a very rare cardiac tumor. Various combinations of treatments including resection or transplant surgery and Chemotherapy have been advocated. We report a case of a man who presented with pulmonary embolism secondary to right atrial leiomyosarcoma. He was managed by excision of the tumor and reconstruction of the right atrium with autologous pericardium. Postoperatively tumor dissemination was controlled with adjuvant chemotherapy