Center for Discrete Mathematics and Theoretical Computer Science

OBJECTIVE: To evaluate a new 2-step technique for obtaining adequate but short-term parenchymal hypertrophy in oncologic patients requiring extended right hepatic resection with limited functional reserve. BACKGROUND: Patients presenting with primary or metastatic liver tumors often face the dilemma that the remaining liver tissue may not be sufficient. Preoperative portal vein embolization has thus far been established as the standard procedure for achieving resectability. METHODS: Two-staged hepatectomy was performed in patients who preoperatively appeared to be marginally resectable but had a tumor-free left lateral lobe. Marginal respectability was defined as a left lateral lobe to body weight ratio of less than 0.5. In the first step, surgical exploration, right portal vein ligation (PVL), and in situ splitting (ISS) of the liver parenchyma along the falciform ligament were performed. Computed tomographic volumetry was performed before ISS and before completion surgery. RESULTS: The study included 25 patients with primary liver tumors (hepatocellular carcinoma: n = 3, intrahepatic cholangiocarcinoma: n = 2, extrahepatic cholangiocarcinoma: n = 2, malignant epithelioid hemangioendothelioma: n = 1, gallbladder cancer: n = 1 or metastatic disease [colorectal liver metastasis]: n = 14, ovarian cancer: n = 1, gastric cancer: n = 1). Preoperative CT volumetry of the left lateral lobe showed 310 mL in median (range = 197-444 mL). After a median waiting period of 9 days (range = 5-28 days), the volume of the left lateral lobe had increased to 536 mL (range = 273-881 mL), representing a median volume increase of 74% (range = 21%-192%) (P < 0.001). The median left lateral liver lobe to body weight ratio was increased from 0.38% (range = 0.25%-0.49%) to 0.61% (range = 0.35-0.95). Ten of 25 patients (40%) required biliary reconstruction with hepaticojejunostomy. Rapid perioperative recovery was reflected by normalization of International normalized ratio (INR) (80% of patients), creatinine (84% of patients), nearly normal bilirubin (56% of patients), and albumin (64% of patients) values by day 14 after completion surgery. Perioperative morbidity was classified according to the Dindo-Clavien classification of surgical complications: grade I (12 events), grade II (13 events), grade III (14 events, III a: 6 events, III b: 8 events), grade IV (8 events, IV a: 3 events, IV b: 5 events), and grade V (3 events). Sixteen patients (68%) experienced perioperative complications. Follow-up was 180 days in median (range: 60-776 days) with an estimated overall survival of 86% at 6 months after resection. CONCLUSIONS: Two-step hepatic resection performing surgical exploration, PVL, and ISS results in a marked and rapid hypertrophy of functional liver tissue and enables curative resection of marginally resectable liver tumors or metastases in patients that might otherwise be regarded as palliative.

The recent FCC frequency allocation for UWB has generated a lot of interest in UWB technologies. There is 7,500 MHz of spectrum for unlicensed use. The main limitations are provided by the low-power spectral density and by the fact that the transmit signal must occupy at least 500 MHz at whole times. IEEE 802.15.3a is being developed for high-bit-rate PAN applications, and UWB is the most promising technology to support the stringent requirements: 110, 200, and 480 Mb/s. Two UWB multiband systems, frequency hopping and Spectral Keying, have been described in this article. Both systems meet the stringent requirements provided by IEEE 802.15.

The main theme of this book is the interplay between the behaviour of a class of stochastic processes (random walks) and discrete structure theory. The author considers Markov chains whose state space is equipped with the structure of an infinite, locally finite graph, or as a particular case, of a finitely generated group. The transition probabilities are assumed to be adapted to the underlying structure in some way that must be specified precisely in each case. From the probabilistic viewpoint, the question is what impact the particular type of structure has on various aspects of the behaviour of the random walk. Vice-versa, random walks may also be seen as useful tools for classifying, or at least describing the structure of graphs and groups. Links with spectral theory and discrete potential theory are also discussed. This book will be essential reading for all researchers working in stochastic process and related topics.

Logistic regression analysis of high-dimensional data, such as natural language text, poses computational and statistical challenges. Maximum likelihood estimation often fails in these applications. We present a simple Bayesian logistic regression approach that uses a Laplace prior to avoid overfitting and produces sparse predictive models for text data. We apply this approach to a range of document classification problems and show that it produces compact predictive models at least as effective as those produced by support vector machine classifiers or ridge logistic regression combined with feature selection. We describe our model fitting algorithm, our open source implementations (BBR and BMR), and experimental results.

We present the design of a superconducting qubit that has circulating currents of opposite sign as its two states. The circuit consists of three nanoscale aluminum Josephson junctions connected in a superconducting loop and controlled by magnetic fields. The advantages of this qubit are that it can be made insensitive to background charges in the substrate, the flux in the two states can be detected with a superconducting quantum interference device, and the states can be manipulated with magnetic fields. Coupled systems of qubits are also discussed as well as sources of decoherence.

Stefan Brands proposes cryptographic building blocks for the design of digital certificates that preserve privacy without sacrificing security. As paper-based communication and transaction mechanisms are replaced by automated ones, traditional forms of security such as photographs and handwritten signatures are becoming outdated. Most security experts believe that digital certificates offer the best technology for safeguarding electronic communications. They are already widely used for authenticating and encrypting email and software, and eventually will be built into any device or piece of software that must be able to communicate securely. There is a serious problem, however, with this unavoidable trend: unless drastic measures are taken, everyone will be forced to communicate via what will be the most pervasive electronic surveillance tool ever built. There will also be abundant opportunity for misuse of digital certificates by hackers, unscrupulous employees, government agencies, financial institutions, insurance companies, and so on.In this book Stefan Brands proposes cryptographic building blocks for the design of digital certificates that preserve privacy without sacrificing security. Such certificates function in much the same way as cinema tickets or subway tokens: anyone can establish their validity and the data they specify, but no more than that. Furthermore, different actions by the same person cannot be linked. Certificate holders have control over what information is disclosed, and to whom. Subsets of the proposed cryptographic building blocks can be used in combination, allowing a cookbook approach to the design of public key infrastructures. Potential applications include electronic cash, electronic postage, digital rights management, pseudonyms for online chat rooms, health care information storage, electronic voting, and even electronic gambling.

We address optimization problems in which we are given contradictory pieces of input information and the goal is to find a globally consistent solution that minimizes the extent of disagreement with the respective inputs. Specifically, the problems we address are rank aggregation, the feedback arc set problem on tournaments, and correlation and consensus clustering. We show that for all these problems (and various weighted versions of them), we can obtain improved approximation factors using essentially the same remarkably simple algorithm. Additionally, we almost settle a long-standing conjecture of Bang-Jensen and Thomassen and show that unless NP⊆BPP, there is no polynomial time algorithm for the problem of minimum feedback arc set in tournaments.

This paper presents new graph-theoretic results appropriate for the analysis of a variety of consensus problems cast in dynamically changing environments. The concepts of rooted, strongly rooted, and neighbor-shared are defined, and conditions are derived for compositions of sequences of directed graphs to be of these types. The graph of a stochastic matrix is defined, and it is shown that under certain conditions the graph of a Sarymsakov matrix and a rooted graph are one and the same. As an illustration of the use of the concepts developed in this paper, graph-theoretic conditions are obtained which address the convergence question for the leaderless version of the widely studied Vicsek consensus problem.

A feedback vertex set of a graph is a subset of vertices that contains at least one vertex from every cycle in the graph. The problem considered is that of finding a minimum feedback vertex set given a weighted and undirected graph. We present a simple and efficient approximation algorithm with performance ratio of at most 2, improving previous best bounds for either weighted or unweighted cases of the problem. Any further improvement on this bound, matching the best constant factor known for the vertex cover problem, is deemed challenging. The approximation principle, underlying the algorithm, is based on a generalized form of the classical local ratio theorem, originally developed for approximation of the vertex cover problem, and a more flexible style of its application.

Ultrasound (US) elasticity imaging is an extension of the ancient art of palpation and of earlier US methods for viewing tissue stiffness such as echopalpation. Elasticity images consist of either an image of strain in response to force or an image of estimated elastic modulus. There are 3 main types of US elasticity imaging: elastography that tracks tissue movement during compression to obtain an estimate of strain, sonoelastography that uses color Doppler to generate an image of tissue movement in response to external vibrations, and tracking of shear wave propagation through tissue to obtain the elastic modulus. Other modalities may be used for elasticity imaging, the most powerful being magnetic resonance elastography. With 4 commercial US scanners already offering elastography and more to follow, US-based methods may be the most widely used for the near future. Elasticity imaging is possible for nearly every tissue. Breast mass elastography has potential for enhancing the specificity of US and mammography for cancer detection. Lesions in the thyroid, prostate gland, pancreas, and lymph nodes have been successfully imaged using elastography. Evaluation of diffuse disease including cirrhosis and transplant rejection is also possible using both imaging and nonimaging methods. Vascular imaging including myocardium, blood vessel wall, plaque, and venous thrombi has also shown great potential. Elasticity imaging may also be important in assessing the progress of ablation therapy. Recent work in assessing porous materials using elastography suggests that the technique may be useful in monitoring the severity of lymphedema.

The main focus of this study was to obtain plant produced Reclaimed Asphalt Pavement (RAP) mixtures, to document the mixture production parameters and to evaluate the degree of blending between the virgin and RAP binders. The effect of mixture production parameters on the performance (in terms of stiffness, cracking, rutting, and moisture susceptibility) and workability of the mixtures was evaluated. Eighteen plant produced mixtures were obtained from three locations in the Northeast United States. RAP contents (zero to 40%) were varied and softer binders were used. The data and analysis illustrated that the degree of blending between RAP and virgin binders is a function of production parameters. The stiffness of the mixtures increased as the percentage of RAP increased, but not when the discharge temperatures of the mixtures were inconsistent. The cracking resistance was reduced as the percentage of RAP increased. The rutting and moisture damage resistance improved as the percentage of RAP in the mixtures increased. Finally, reheating the mixtures in the laboratory caused a significant increase in the stiffness of the mixtures.

OBJECTIVE: To update and examine national temporal trends in contralateral prophylactic mastectomy (CPM) and determine whether survival differed for invasive breast cancer patients based on hormone receptor (HR) status and age. METHODS: We identified women diagnosed with unilateral stage I to III breast cancer between 1998 and 2012 within the Surveillance, Epidemiology, and End Results registry. We compared characteristics and temporal trends between patients undergoing breast-conserving surgery, unilateral mastectomy, and CPM. We then performed Cox proportional-hazards regression to examine breast cancer-specific survival (BCSS) and overall survival (OS) in women diagnosed between 1998 and 2007, who underwent breast-conserving surgery with radiation (breast-conserving therapy), unilateral mastectomy, or CPM, with subsequent subgroup analysis stratifying by age and HR status. RESULTS: Of 496,488 women diagnosed with unilateral invasive breast cancer, 59.6% underwent breast-conserving surgery, 33.4% underwent unilateral mastectomy, and 7.0% underwent CPM. Overall, the proportion of women undergoing CPM increased from 3.9% in 2002 to 12.7% in 2012 (P < 0.001). Reconstructive surgery was performed in 48.3% of CPM patients compared with only 16.0% of unilateral mastectomy patients, with rates of reconstruction with CPM rising from 35.3% in 2002 to 55.4% in 2012 (P < 0.001). When compared with breast-conserving therapy, we found no significant improvement in BCSS or OS for women undergoing CPM (BCSS: HR 1.08, 95% confidence interval 1.01-1.16; OS: HR 1.08, 95% confidence interval 1.03-1.14), regardless of HR status or age. CONCLUSIONS: The use of CPM more than tripled during the study period despite evidence suggesting no survival benefit over breast conservation. Further examination on how to optimally counsel women about surgical options is warranted.

Given a high dimensional convex body K⊆ℝn by a separation oracle, we can approximate its volume with relative error ε, using O*(n5) oracle calls. Our algorithm also brings the body into isotropic position. As all previous randomized volume algorithms, we use “rounding” followed by a multiphase Monte-Carlo (product estimator) technique. Both parts rely on sampling (generating random points in K), which is done by random walk. Our algorithm introduces three new ideas: the use of the isotropic position (or at least an approximation of it) for rounding; the separation of global obstructions (diameter) and local obstructions (boundary problems) for fast mixing; and a stepwise interlacing of rounding and sampling. © 1997 John Wiley & Sons, Inc. Random Struct. Alg., 11, 1–50, 1997

Abstract Control rules governing transciption of eukaryotic genes can be modeled as Boolean function, and these rules are strongly biased toward large numbers of “canalizing” inputs. The ensemble of networks with the observed canalizing bias predicts cells are in an ordered regime with convergent flow in transcription state space, a percolating subnetwork of genes fixed on or off an isolated islands of twinkling genes turning on or off, and a near power‐law distribution of cascades of gene activity changes following perturbations. The data suggest that a given cell state or type can be represented as an attractor of transcriptional activity or flow over time. © 2002 Wiley Periodicals, Inc.

A computational method has been developed for the assignment of a protein sequence to a folding class in the Structural Classification of Proteins (SCOP). This method uses global descriptors of a primary protein sequence in terms of the physical, chemical, and structural properties of the constituent amino acids. Neural networks are utilized to combine these descriptors in a way to discriminate members of a given fold from members of all other folds. An extensive testing of the method has been performed to evaluate its prediction accuracy. The method is applicable for the fold assignment of any protein sequence with or without significant sequence homology to known proteins. A WWW page for predicting protein folds is available at URL http://cbcg.lbl.gov/. Proteins 1999;35:401–407.

A new scalable modeling framework and scalable parallel simulations make it possible to analyze the detailed behaviour of large, multidomain multiprotocol Internet models. The article focuses on simulation research. It describes the software designs that let us construct and run appropriately large models. After several years of research, we have developed a scalable network modeling framework, a scalable simulation framework (SSF), and scalable parallel discrete event simulators capable of modeling the Internet at unprecedented scales.

OBJECTIVE: The aim of this study is to evaluate long-term oncologic outcomes of robotic surgery for rectal cancer compared with laparoscopic surgery at a single institution. BACKGROUND: Robotic surgery is regarded as a new modality to surpass the technical limitations of conventional surgery. Short-term outcomes of robotic surgery for rectal cancer were acceptable in previous reports. However, evidence of long-term feasibility and oncologic safety is required. METHODS: Between April 2006 and August 2011, 217 patients who underwent minimally invasive surgery for rectal cancer with stage I-III disease were enrolled prospectively (robot, n = 133; laparoscopy, n = 84). Median follow-up period was 58 months (range, 4-80 months). Perioperative clinicopathologic outcomes, morbidities, 5-year survival rates, prognostic factors, and cost were evaluated. RESULTS: Perioperative clinicopathologic outcomes demonstrated no significant differences except for the conversion rate and length of hospital stay. The 5-year overall survival rate was 92.8% in robotic, and 93.5% in laparoscopic surgical procedures (P = 0.829). The 5-year disease-free survival rate was 81.9% and 78.7%, respectively (P = 0.547). Local recurrence was similar: 2.3% and 1.2% (P = 0.649). According to the univariate analysis, this type of surgical approach was not a prognostic factor for long-term survival. The patient's mean payment for robotic surgery was approximately 2.34 times higher than laparoscopic surgery. CONCLUSIONS: No significant differences were found in the 5-year overall, disease-free survival and local recurrence rates between robotic and laparoscopic surgical procedures. We concluded that robotic surgery for rectal cancer failed to offer any oncologic or clinical benefits as compared with laparoscopy despite an increased cost.

Given an arc-weighted directed graph G = (V, A, /spl lscr/) and a pair of nodes s, t, we seek to find an s-t walk of length at most B that maximizes some given function f of the set of nodes visited by the walk. The simplest case is when we seek to maximize the number of nodes visited: this is called the orienteering problem. Our main result is a quasi-polynomial time algorithm that yields an O(log OPT) approximation for this problem when f is a given submodular set function. We then extend it to the case when a node v is counted as visited only if the walk reaches v in its time window [R(v), D(v)]. We apply the algorithm to obtain several new results. First, we obtain an O(log OPT) approximation for a generalization of the orienteering problem in which the profit for visiting each node may vary arbitrarily with time. This captures the time window problem considered earlier for which, even in undirected graphs, the best approximation ratio known [Bansal, N et al. (2004)] is O(log/sup 2/ OPT). The second application is an O(log/sup 2/ k) approximation for the k-TSP problem in directed graphs (satisfying asymmetric triangle inequality). This is the first non-trivial approximation algorithm for this problem. The third application is an O(log/sup 2/ k) approximation (in quasi-poly time) for the group Steiner problem in undirected graphs where k is the number of groups. This improves earlier ratios (Garg, N et al.) by a logarithmic factor and almost matches the inapproximability threshold on trees (Halperin and Krauthgamer, 2003). This connection to group Steiner trees also enables us to prove that the problem we consider is hard to approximate to a ratio better than /spl Omega/(log/sup 1-/spl epsi// OPT), even in undirected graphs. Even though our algorithm runs in quasi-poly time, we believe that the implications for the approximability of several basic optimization problems are interesting.

Recent studies of human cancers and mutant mouse models have implicated the Nkx3.1 homeobox gene as having a key role in prostate carcinogenesis. Consistent with such a role, here we show that Nkx3.1 displays growth-suppressing activities in cell culture, and that aged Nkx3.1 mutant mice display histopathological defects resembling prostatic intraepithelial neoplasia (PIN), the presumed precursor of human prostate cancer. Using a tissue recombination approach, we found that PIN-like lesions from Nkx3.1 mutants can undergo progressively severe histopathological alterations after serial transplantation in nude mice. Our findings indicate that Nkx3.1 loss-of-function is a critical event in prostate cancer initiation, and that Nkx3.1 mutant mice accurately model early stages of prostate carcinogenesis. More generally, our tissue recombination assay provides an empirical test to examine the relationship of PIN to prostate carcinoma.

In Brief Objective: To study the differences in short and long-term outcomes of transthoracic and transhiatal esophagectomy for cancer. Background: Studies have compared transthoracic with transhiatal esophagectomy with varying results. Previous systematic reviews (1999, 2001) do not include the latest randomized controlled trials. Methods: Systematic review of English-language studies comparing transthoracic with transhiatal esophagectomy up to January 31, 2010. Meta-analysis was used to summate the study outcomes. Methodological and surgical quality of included studies was assessed. Results: Fifty-two studies, comprising 5905 patients (3389 transthoracic and 2516 transhiatal) were included in the analysis. No study met all minimum surgical quality standards. Transthoracic operations took longer and were associated with a significantly longer length of stay. There was no difference in blood loss. The transthoracic group had significantly more respiratory complications, wound infections, and early postoperative mortality, whereas anastomotic leak, anastomotic stricture, and recurrent laryngeal nerve palsy rate was significantly higher in the transhiatal group. Lymph node retrieval was reported in 4 studies and was significantly greater in the transthoracic group by on average 8 lymph nodes. Analysis of 5-year survival showed no significant difference between the groups and was subject to significant heterogeneity. Conclusions: This meta-analysis of studies comparing transthoracic with transhiatal esophagectomy for cancer demonstrates no difference in 5-year survival, however lymphadenectomy and reported surgical quality was suboptimal in both groups and the transthoracic group had significantly more advanced cancer. The finding of equivalent survival should therefore be viewed with caution. This meta-analysis of studies comparing transthoracic with transhiatal esophagectomy for cancer demonstrates no difference in 5-year survival, however lymphadenectomy and reported surgical quality was suboptimal in both groups and the transthoracic group had significantly more advanced cancer. The finding of equivalent survival should therefore be viewed with caution.