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

Binarity as a key factor in protoplanetary disk evolution: Spitzer disk census of the eta Chamaeleontis cluster

The formation of planets is directly linked to the evolution of the circumstellar (CS) disk from which they are born. The dissipation timescales of CS disks are, therefore, of direct astrophysical importance in evaluating the time available for planet formation. We employ Spitzer Space Telescope spectra to complete the CS disk census for the late-type members of the ~8 Myr-old eta Chamaeleontis star cluster. Of the 15 K- and M-type members, eight show excess emission. We find that the presence of a CS disk is anti-correlated with binarity, with all but one disk associated with single stars. With nine single stars in total, about 80% retain a CS disk. Of the six known or suspected close binaries the only CS disk is associated with the primary of RECX 9. No circumbinary disks have been detected. We also find that stars with disks are slow rotators with surface values of specific angular momentum j = 2-15 j_sun. All high specific angular momentum systems with j = 20-30 j_sun are confined to the primary stars of binaries. This provides novel empirical evidence for rotational disk locking and again demonstrates the much shorter disk lifetimes in close binary systems compared to single star systems. We estimate the characteristic mean disk dissipation timescale to be ~5 Myr and ~9 Myr for the binary and single star systems, respectively.Comment: Accepted by ApJ

Investigating prostate cancer tumour-stroma interactions - clinical and biological insights from an evolutionary game

BACKGROUND: Tumours are made up of a mixed population of different types of cells that include normal structures as well as ones associated with the malignancy, and there are multiple interactions between the malignant cells and the local microenvironment. These intercellular interactions, modulated by the microenvironment, effect tumour progression and represent a largely under appreciated therapeutic target. We use observations of primary tumor biology from prostate cancer to extrapolate a mathematical model: specifically; it has been observed that in prostate cancer three disparate cellular outcomes predominate: (i) the tumour remains well differentiated and clinically indolent - in this case the local stromal cells may act to restrain the growth of the cancer; (ii) early in its genesis the tumour acquires a highly malignant phenotype, growing rapidly and displacing the original stromal population (often referred to as small cell prostate cancer) - these less common aggressive tumours are relatively independent of the local microenvironment; and, (iii) the tumour co-opts the local stroma - taking on a classic stromagenic phenotype where interactions with the local microenvironment are critical to the cancer growth. METHODS: We present an evolutionary game theoretical construct that models the influence of tumour-stroma interactions in driving these outcomes. We consider three characteristic and distinct cellular populations: stromal cells, tumour cells that are self-reliant in terms of microenvironmental factors and tumour cells that depend on the environment for resources but can also co-opt stroma. 
RESULTS: Using evolutionary game theory we explore a number of different scenarios that elucidate the impact of tumour-stromal interactions on the dynamics of prostate cancer growth and progression and how different treatments in the metastatic setting can affect different types of tumors.
CONCLUSIONS: The tumour microenvironment plays a crucial role selecting the traits of the tumour cells that will determine prostate cancer progression. Equally important, treatments like hormone therapy affect the selection of these cancer phenotypes making it very important to understand how they impact prostate cancer’s somatic evolution

Evidence for proteolytic cleavage of brevican by the ADAMTSs in the dentate gyrus after excitotoxic lesion of the mouse entorhinal cortex

BACKGROUND: Brevican is a member of the lectican family of aggregating extracellular matrix (ECM) proteoglycans that bear chondroitin sulfate (CS) chains. It is highly expressed in the central nervous system (CNS) and is thought to stabilize synapses and inhibit neural plasticity and as such, neuritic or synaptic remodeling would be less likely to occur in regions with intact and abundant, lectican-containing, ECM complexes. Neural plasticity may occur more readily when these ECM complexes are broken down by endogenous proteases, the ADAMTSs (adisintegrin and metalloproteinase with thrombospondin motifs), that selectively cleave the lecticans. The purpose of these experiments was to determine whether the production of brevican or the ADAMTS-cleaved fragments of brevican were altered after deafferentation and reinnervation of the dentate gyrus via entorhinal cortex lesion (ECL). RESULTS: In the C57Bl6J mouse, synaptic density in the molecular layer of the dentate gyrus, as measured by synaptophysin levels in ELISA, was significantly attenuated 2 days (nearly 50% of contralateral) and 7 days after lesion and returned to levels not different from the contralateral region at 30 days. Immunoreactive brevican in immunoblot was elevated 2 days after lesion, whereas there was a significant increase in the proteolytic product at 7, but not 30 days post-lesion. ADAMTS activity, estimated using the ratio of the specific ADAMTS-derived brevican fragment and intact brevican levels was increased at 7 days, but was not different from the contralateral side at 2 or 30 days after deafferentation. CONCLUSION: These findings indicate that ADAMTS activity in the dentate outer molecular layer (OML) is elevated during the initial synaptic reinnervation period (7 days after lesion). Therefore, proteolytic processing of brevican appears to be a significant extracellular event in the remodeling of the dentate after EC lesion, and may modulate the process of sprouting and/or synaptogenesis

The stability of a cubic fixed point in three dimensions from the renormalization group

The global structure of the renormalization-group flows of a model with isotropic and cubic interactions is studied using the massive field theory directly in three dimensions. The four-loop expansions of the \bt-functions are calculated for arbitrary $N$. The critical dimensionality $N_c=2.89 \pm 0.02$ and the stability matrix eigenvalues estimates obtained on the basis of the generalized Pad$\acute{\rm e}$-Borel-Leroy resummation technique are shown to be in a good agreement with those found recently by exploiting the five-loop \ve-expansions.Comment: 18 pages, LaTeX, 5 PostScript figure

On the spectrum of Farey and Gauss maps

In this paper we introduce Hilbert spaces of holomorphic functions given by generalized Borel and Laplace transforms which are left invariant by the transfer operators of the Farey map and its induced version, the Gauss map, respectively. By means of a suitable operator-valued power series we are able to study simultaneously the spectrum of both these operators along with the analytic properties of the associated dynamical zeta functions.Comment: 23 page