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Background: Expansion in liver transplantation (LT) criteria for HCC from Milan to UCSF has not adversely impacted overall survival, prompting further expansion towards Metroticket 2.0 (MT2). In this study, we compared patient survival post-transplant before and after 2007 and long-term outcomes for LT within Milan versus UCSF criteria (to determine the true benefit of the expansion of criteria) and retrospectively validated the MT2 criteria. Methods: Retrospective analysis of ANZLITR (including all patients transplanted for HCC since July 1997). The entire cohort was divided based on criteria used at the time of listing, namely, Milan era (1997–2006) and the UCSF era (2007–July 2015). Results: The overall 5- and 10-year cumulative survival rates for the entire cohort of 691 patients were 78% and 69%, respectively. Patients transplanted in UCSF era had significantly higher 5- and 10-year survival rates than in the Milan era (80% vs. 73% and 72% vs. 65%, respectively; p = 0.016). In the UCSF era, the 5-year survival rate for patients transplanted within Milan criteria was significantly better than those transplanted outside Milan but within UCSF criteria (83% vs. 73%; p < 0.024). Patients transplanted within the MT2 criteria had a significantly better 5- and 10-year survival rate as compared to those outside the criteria (81% vs. 64% and 73% vs. 50%, respectively; p = 0.001). Conclusion: Overall survival following LT for HCC has significantly improved over time despite expanding criteria from Milan to UCSF. Patients fulfilling the MT2 criteria have a survival comparable to the UCSF cohort. Thus, expansion of criteria to MT2 is justifiable.

With the advancement of storage and processing technology, an enormous amount of data is collected on a daily basis in many applications. Nowadays, advanced data analytics have been used to mine the collected data for useful information and make predictions, contributing to the competitive advantages of companies. The increasing data volume, however, has posed many problems to classical batch learning systems, such as the need to retrain the model completely with the newly arrived samples or the impracticality of storing and accessing a large volume of data. This has prompted interest on incremental learning that operates on data streams. In this study, we develop an incremental online multi-label classification (OMLC) method based on a weighted clustering model. The model is made to adapt to the change of data via the decay mechanism in which each sample's weight dwindles away over time. The clustering model therefore always focuses more on newly arrived samples. In the classification process, only clusters whose weights are greater than a threshold (called mature clusters) are employed to assign labels for the samples. In our method, not only is the clustering model incrementally maintained with the revealed ground truth labels of the arrived samples, the number of predicted labels in a sample are also adjusted based on the Hoeffding inequality and the label cardinality. The experimental results show that our method is competitive compared to several well-known benchmark algorithms on six performance measures in both the stationary and the concept drift settings.

Liver transplantation (LT) for small infants remains challenging because of the demands related to graft selection, surgical technique, and perioperative management. The aim of this study was to evaluate the short‐term and longterm outcomes of LT regarding vascular/biliary complications, renal function, growth, and patient/graft survival in infants ≤3 months compared with those of an age between >3 and 6 months at a single transplant center. A total of 64 infants ≤6 months underwent LT and were divided into 2 groups according to age at LT: those of age ≤3 months (range, 6‐118 days; XS group, n = 37) and those of age >3 to ≤6 months (range, 124‐179 days; S group, n = 27) between 1989 and 2014. Acute liver failure was the main indication for LT in the XS group (n = 31, 84%) versus S (n = 7, 26%). The overall incidence of hepatic artery thrombosis and portal vein thrombosis/stricture were 5.4% and 10.8% in the XS group and 7.4% and 11.1% in the S group, respectively (not significant). The overall incidence of biliary stricture and leakage were 5.4% and 2.7% in the XS group and 3.7% and 3.7% in the S group, respectively (not significant). There was no significant difference between the 2 groups in terms of renal function. No significant difference was found between the 2 groups for each year after LT in terms of height and weight z score. The 1‐, 5‐, and 10‐year patient survival rates were 70.3%, 70.3%, and 70.3% in the XS group compared with 92.6%, 88.9%, and 88.9% in the S group, respectively (not significant). In conclusion, LT for smaller infants has acceptable outcomes despite the challenges of surgical technique, including vascular reconstruction and graft preparation, and perioperative management.

The application of finite element analysis is used to simulate the relative distribution and magnitude of stress–strain conditions during a geologically brief, NNW-SSE-oriented, extensional event (1595 Ma to 1590 Ma), co-incident with IOCG-hydrothermal fluid flow and mineralisation across the Mt Woods Inlier, Gawler Craton, South Australia. Differential stress and shear strain maps across the modelled terrane highlight regions that were predisposed to strain localization, extensional failure and fluid throughput during the simulated mineralisation event. These maps are integrated with other datasets and interpretation layers, one of which is a proposed structural–geometrical relationship apparent in many world-class IOCG deposits, including Prominent Hill, Olympic Dam, Sossego, Salobo, Cristalino and Candelaria. These deposits occur at steeply plunging, pipe-like intersections of conjugate extensional systems of faults, shears and/or contacts, wherein the obtuse angle may have been bisected by the maximum principal extensional axis (viz., σ3) during mineralisation. Several other layers are also used for the generation of targets, such as distance from major shear zones, favourable host lithologies, and proximity to tectonostratigraphic contacts of markedly contrasting competency. The result is an integrated target index or heat map for IOCG prospectively across the Mt. Woods Inlier.

Funding: This work was supported by the EU Horizon 2020 project, TeamPlay, Grant Number 779882, and UK EPSRC Discovery, Grant Number EP/P020631/1. This paper presents a new technique for introducing and tuning parallelism for heterogeneous shared-memory systems (comprising a mixture of CPUs and GPUs), using a combination of algorithmic skeletons (such as farms and pipelines), Monte–Carlo tree search for deriving mappings of tasks to available hardware resources, and refactoring tool support for applying the patterns and mappings in an easy and effective way. Using our approach, we demonstrate easily obtainable, significant and scalable speedups on a number of case studies showing speedups of up to 41 over the sequential code on a 24-core machine with one GPU. We also demonstrate that the speedups obtained by mappings derived by the MCTS algorithm are within 5–15% of the best-obtained manual parallelisation. Publisher PDF

We present a new variant of the Vehicle Routing Problem based on a real industrial scenario. This VRP is dynamic and heavily constrained and uses time-windows, a heterogeneous vehicle fleet and multiple types of job. A constructive solver is developed and tested using dynamic simulation of real-world data from a leading Scottish haulier. Our experiments establish the efficiency and reliability of the method for this problem. Additionally, a methodology for evaluating policy changes through simulation is presented, showing that our technique supports operations and management. We establish that fleet size can be reduced or more jobs handled by the company.

Fitness modeling has received growing interest from the evolutionary computation community in recent years. With a fitness model, one can improve evolutionary algorithm efficiency by directly sampling new solutions, developing hybrid guided evolutionary operators or using the model as a surrogate for an expensive fitness function. This paper addresses several issues on fitness modeling of discrete functions, particularly how modeling quality and efficiency can be improved. We define the Markov network fitness model in terms of Walsh functions. We explore the relationship between the Markov network fitness model and fitness in a number of discrete problems, showing how the parameters of the fitness model can identify qualitative features of the fitness function. We define the fitness prediction correlation, a metric to measure fitness modeling capability of local and global fitness models. We use this metric to investigate the effects of population size and selection on the tradeoff between model quality and complexity for the Markov network fitness model.

Objectives: To construct new prostate cancer staging lookup tables based on a dataset collated by the British Association of Urological Surgeons (BAUS) and to validate them and compare their predictive power with Partin tables. Patients and methods: Complete data on 1701 patients was collated between 1999 and 2008 across 57 UK centres. Lookup tables were created for prediction of pathological stage (PS) using PSA level, biopsy Gleason score (GS) and clinical stage, replicating Partin's original approach. Tables were generated using logistic regression (LR) and bootstrap resampling methods and were internally validated and externally validated using concordance indices (CI) and area under the receiver operating characteristic curve (AUROC) respectively. Results: The CI and AUROC analyses indicate that Partin tables performed poorly on UK data in comparison with US data. The UK prostate cancer tables performed better than Partin tables but the predictive power of all models was relatively poor. Conclusion: The study shows that the predictive power of Partin tables is reduced when applied to the UK population. Models generated using LR methodology have fundamental limitations, and we suggest alternative modelling methods such as Bayesian networks.

Objectives: Prediction of prostate cancer pathological stage is an essential step in a patient's pathway. It determines the treatment that will be applied further. In current practice, urologists use the pathological stage predictions provided in Partin tables to support their decisions. However, Partin tables are based on logistic regression (LR) and built from US data. Our objective is to investigate a range of both predictive methods and of predictive variables for pathological stage prediction and assess them with respect to their predictive quality based on UK data. Methods and material: The latest version of Partin tables was applied to a large scale British dataset in order to measure their performances by mean of concordance index (c-index). The data was collected by the British Association of Urological Surgeons (BAUS) and gathered records from over 1700 patients treated with prostatectomy in 57 centers across UK. The original methodology was replicated using the BAUS dataset and evaluated using concordance index. In addition, a selection of classifiers, including, among others, LR, artificial neural networks and Bayesian networks (BNs) was applied to the same data and compared with each other using the area under the ROC curve (AUC). Subsets of the data were created in order to observe how classifiers perform with the inclusion of extra variables. Finally a local dataset prepared by the Aberdeen Royal Infirmary was used to study the effect on predictive performance of using different variables. Results: Partin tables have low predictive quality (c-index=0.602) when applied on UK data for comparison on patients with organ confined and extra prostatic extension conditions, patients at the two most frequently observed pathological stages. The use of replicate lookup tables built from British data shows an improvement in the classification, but the overall predictive quality remains low (c-index=0.610). Comparing a range of classifiers shows that BNs generally outperform other methods. Using the four variables from Partin tables, naive Bayes is the best classifier for the prediction of each class label (AUC=0.662 for OC). When two additional variables are added, the results of LR (0.675), artificial neural networks (0.656) and BN methods (0.679) are overall improved. BNs show higher AUCs than the other methods when the number of variables raises Conclusion: The predictive quality of Partin tables can be described as low to moderate on UK data. This means that following the predictions generated by Partin tables, many patients would received an inappropriate treatment, generally associated with a deterioration of their quality of life. In addition to demographic differences between UK and the original US population, the methodology and in particular LR present limitations. BN represents a promising alternative to LR from which prostate cancer staging can benefit. Heuristic search for structure learning and the inclusion of more variables are elements that further improve BN models quality.

This paper presents a Markov random field (MRF) approach to estimating and sampling the probability distribution in populations of solutions. The approach is used to define a class of algorithms under the general heading distribution estimation using Markov random fields (DEUM). DEUM is a subclass of estimation of distribution algorithms (EDAs) where interaction between solution variables is represented as an undirected graph and the joint probability of a solution is factorized as a Gibbs distribution derived from the structure of the graph. The focus of this paper will be on describing the three main characteristics of DEUM framework, which distinguishes it from the traditional EDA. They are: 1) use of MRF models, 2) fitness modeling approach to estimating the parameter of the model and 3) Monte Carlo approach to sampling from the model.

Genetic algorithms (GAs) are a heuristic search and optimisation technique inspired by natural evolution. They have been successfully applied to a wide range of real-world problems of significant complexity. This paper is intended as an introduction to GAs aimed at immunologists and mathematicians interested in immunology. We describe how to construct a GA and the main strands of GA theory before speculatively identifying possible applications of GAs to the study of immunology. An illustrative example of using a GA for a medical optimal control problem is provided. The paper also includes a brief account of the related area of artificial immune systems.

Background Little is known about the pattern of injury in short track speed skating. Purpose To investigate the incidence and characteristics of injuries in short track speed skating. Study Design Retrospective study. Methods Ninety-five of 150 elite-level skaters (63.3%) were surveyed to collect information on training and competition load as well as on injuries sustained during the 1999—2000 competitive season. Injuries were characterized in terms of anatomic location, type of injury, time loss from training and competition, and circumstance of injury (acute onset during competition, on-ice practice, off-ice training, or insidious onset). Results Sixty-one of the 95 skaters (64.2%) reported sustaining at least one injury. The knee, ankle, spine, leg, and groin were the most commonly reported sites of injury. Skaters were also asked to list previous on-ice injuries. The two most common injuries occurring on-ice before the 1999—2000 season were lacerations from the knee down (11.1%) and ankle fractures (10.2%). Conclusion The results of this study suggest that there is a high incidence of injury in competitive short track speed skating.

Background The outcome of treatment for advanced hepatoblastoma has recently improved after the introduction of preoperative or pre- and postoperative cisplatin-containing chemotherapy combined with complete surgical excision. The role of liver transplantation in a population of patients who have received this regimen has not been clearly defined. Methods Orthotopic liver transplantation (OLT) was performed in 13 children, aged 5 months to 11 years (median 27 months), who were assessed with unresectable hepatoblastoma, and whose pretreatment extent-of-disease was based on radiologic findings of group III (n=11) and group IV (n=2). One child with a multifocal tumor showed pulmonary metastases at presentation, but, according to radiologic studies, the deposits resolved with chemotherapy before liver transplantation. One other child showed exophytic extension of the primary tumor infiltrating the porta hepatis and body of the pancreas. All 13 patients received preoperative chemotherapy to reduce the size of the primary tumor(s) and to treat metastatic spread. Results Twelve children underwent elective OLT; all are alive and show normal graft function at a mean follow-up of 33 months (range 1-108). One child shows evidence of recurrent disease in the form of pulmonary metastases. One child underwent emergency OLT for acute liver failure after (incomplete) extended right hepatectomy and died from respiratory failure, with no evidence of recurrent tumor 3 weeks posttransplant. Conclusions Liver transplantation is an effective treatment for unresectable unifocal or multifocal hepatoblastoma confined to the liver. A multidisciplinary approach to the management of hepatoblastoma, with thoughtful collaboration between pediatric oncologists, hepatologists, and liver surgeons, is essential.

It is controversial whether prolonged antibiotic treatment is effective for patients in whom symptoms persist after the recommended antibiotic treatment for acute Lyme disease.We conducted two randomized trials: one in 78 patients who were seropositive for IgG antibodies to Borrelia burgdorferi at the time of enrollment and the other in 51 patients who were seronegative. The patients received either intravenous ceftriaxone, 2 g daily for 30 days, followed by oral doxycycline, 200 mg daily for 60 days, or matching intravenous and oral placebos. Each patient had well-documented, previously treated Lyme disease but had persistent musculoskeletal pain, neurocognitive symptoms, or dysesthesia, often associated with fatigue. The primary outcome measures were improvement on the physical- and mental-health-component summary scales of the Medical Outcomes Study 36-item Short-Form General Health Survey (SF-36)--a scale measuring the health-related quality of life--on day 180 of the study.After a planned interim analysis, the data and safety monitoring board recommended that the studies be discontinued because data from the first 107 patients indicated that it was highly unlikely that a significant difference in treatment efficacy between the groups would be observed with the planned full enrollment of 260 patients. Base-line assessments documented severe impairment in the patients' health-related quality of life. In intention-to-treat analyses, there were no significant differences in the outcomes with prolonged antibiotic treatment as compared with placebo. Among the seropositive patients who were treated with antibiotics, there was improvement in the score on the physical-component summary scale of the SF-36, the mental-component summary scale, or both in 37 percent, no change in 29 percent, and worsening in 34 percent; among seropositive patients receiving placebo, there was improvement in 40 percent, no change in 26 percent, and worsening in 34 percent (P=0.96 for the comparison between treatment groups). The results were similar for the seronegative patients.There is considerable impairment of health-related quality of life among patients with persistent symptoms despite previous antibiotic treatment for acute Lyme disease. However, in these two trials, treatment with intravenous and oral antibiotics for 90 days did not improve symptoms more than placebo.

In recent years much work has been don; on modelling the growth of malignant tumours with a view to predicting their development and optimizing the effect of chemotherapy on their alleviation. One approach has been to treat the tumour as a non‐linear system and the drug treatment as a control strategy. This has led to the use of calculus of variations and optimization techniques to produce optimal and sub‐optimal drug regimes. This paper uses the Gompertz equation as a model of tumour growth and attempts to minimize final tumour size in the presence of drug constraints. The optimization technique is novel in that it uses the genetic algorithm method to devise optimal drug regimes where individual regimes are encoded as ‘chromosomes’ and evolution is simulated in order to improve treatment strategies.

To assess the outcomes of patients undergoing percutaneous renal artery embolization (PRAE) prior to radical nephrectomy.We performed retrospective chart review of patients undergoing PRAE in Auckland Public Hospital from January 2004 to December 2011. PRAE was performed under epidural anaesthesia and within 24 h of nephrectomy. We compared our perioperative outcomes with the published literature.Forty-two patients were identified in this series. Patients had predominantly more advanced stage disease with 30 (71%) being T3 or higher (TNM staging). Median operation time was 192 min (range 84-428). 45.2% of patients experienced complications from the surgery. There were no complications associated with PRAE.PRAE prior to nephrectomy is a safe procedure. There is no convincing evidence in the literature that the benefits outweigh the risks. All published studies are non-randomized and subject to selection bias, so the true role of PRAE has not yet been determined and routine use is probably not justified.

The aim of present paper was to document the incidence of gall bladder cancer, cancer of the extrahepatic bile ducts and ampullary carcinoma in New Zealand.Data were collected from the New Zealand Cancer Registry from 1980 to 1997 and combined with national census statistics to give crude and age standardized incidence rates.Over the 18-year study period, 226 carcinomas of the ampulla of Vater, 608 gall bladder cancers, and 486 extrahepatic cholangiocarcinomas were registered. The age standardized incidence rates for gall bladder carcinoma in all New Zealanders were 0.41/100 000 in men and 0.74/100 000 in women. The age standardized incidence rates for gall bladder cancer in Maori were 1.49/100 000 in Maori men and 1.59/100 000 in Maori women. The corresponding age standardized incidence rates for extrahepatic bile duct cancers were 0.67/100 000 in men and 0.45/100 000 in women. There were insufficient cases to calculate an age standardized incidence in Maori or Pacific Islanders. For carcinoma of the ampulla, the age standardized rates were 0.34/100 000 in men and 0.25/100 000 in women. There were insufficient cases to calculate an age standardized incidence rate for Maori or Pacific Islanders. When histology was defined adenocarcinoma was the most common form of cancer occurring in 66% of gall bladder cancers, 91% of extrahepatic bile duct cancers and 70% of ampullary cancers. Most tumours were advanced at presentation with regional or distant metastases present in 72% of gall bladder cancers, 63% of extrahepatic bile duct cancers and 69% of ampullary tumours at diagnosis. Survival was poor with median survivals of 86 days, 151 days and 440 days recorded for gall bladder cancer, extrahepatic bile duct cancer and ampullary cancer, respectively.The demographic profile, pathology and survival of patients with gall bladder cancer, extrahepatic bile duct cancer and ampullary carcinoma are similar in New Zealand to that of other Western countries. However New Zealand Maori have a relatively high incidence of gall bladder cancer, and the incidence is equal in both Maori men and women, while cancers of the extra-hepatic bile duct and ampulla of Vater are rare in Maori. In comparison, cancers of the gall bladder, extrahepatic bile ducts and ampulla are rare in Pacific Islanders.

Inelastic differential scattering cross sections for the system potassium + alkyl halide have been measured in the small angle region for Eχ between 20–1000 eV°. Electronic excitation of both collision partners is seen together with vibrational excitation of the alkyl halide.Evidence is adduced suggesting that excitation occurs by either of two paths corresponding to the preliminary transfer of an electron in the entrance channel or as the colliding pair recedes. A harpooning model incorporating bond stretching in the negative molecular ion is developed that agrees well with most of the observations.

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The paper presents results from an examination of teacher flows within a large city school system. The focus is primarily on the mobility of teachers among schools within the system, the movement of teachers into and out of the system, and the effect of these flows on the allocation of teachers among different types of schools. The data cover the movement of teachers in San Diego between the 1970-71 and 1971-72 school years. However, the theoretical framework used and many of the empirical results should be directly relevant to school personnel systems in large cities throughout the United States.

This paper examines several aspects of the training and retention of Air Force electronic specialists. The major goal of the study is to investigate the responsiveness of the re-enlistment rate to changes in Air Force remuneration. The study is based on data obtained from the Personnel Research Laboratory at Lackland Air Force Base. Both biographical and earnings information were available for a group of 505 electronic specialists who left the Air Force in 1962 after their first tour of duty and who reported their civilian earnings in 1964. Biographical data were also obtained for a control group of 393 electronic specialists who chose to re-enlist in 1962 after their first tour of duty. For this sample of airmen, the re-enlistment rate is very sensitive to differences between civilian and Air Force earnings opportunities. Our results imply, for example, that if the initial re-enlistment rate were 50 percent and if Air Force remuneration were increased by $1,000 per year, then the re-enlistment rate would rise to about 70 percent.