Alexander representation of tangles

A tangle is an oriented 1-submanifold of the cylinder whose endpoints lie on the two disks in the boundary of the cylinder. Using an algebraic tool developed by Lescop, we extend the Burau representation of braids to a functor from the category of oriented tangles to the category of Z[t,t^{-1}]-modules. For (1,1)-tangles (i.e., tangles with one endpoint on each disk) this invariant coincides with the Alexander polynomial of the link obtained by taking the closure of the tangle. We use the notion of plat position of a tangle to give a constructive proof of invariance in this case.Comment: 13 pages, 5 figure

Rethinking neoadjuvant chemotherapy for breast cancer

Breast cancer is the most common cancer in women worldwide. In 2014, 55 000 women in the UK were given the diagnosis of breast cancer, and 11 000 died.1 Early breast cancer is traditionally treated with surgery, plus radiotherapy and adjuvant systemic therapy as required. Neoadjuvant chemotherapy for breast cancer is a new strategy that was introduced towards the end of the 20th century with the aim of reducing tumour size. It has four main rationales. Firstly, it should render an otherwise inoperable tumour operable or, secondly, allow more conservative surgery. Thirdly, starting systemic treatment preoperatively was hoped to lead to improved overall survival in patients with locally advanced cancers, who are at high risk of having distant disease. Finally, unlike adjuvant chemotherapy given in the absence of any measurable disease, neoadjuvant chemotherapy gives us the opportunity to observe the tumour shrink both palpably and on imaging, enabling a rapid assessment of clinical response. This could help test responses in vivo to new drug regimens, which could then be used as adjuvant therapies, in so called window of opportunity studies. A survey of multidisciplinary teams in Australia, Germany, Italy, the UK, and the US found that 7-27% of new breast cancers are treated with neoadjuvant chemotherapy (Saunders C, Cody H, Kolberg HC, et al, personal communication, 2017). With 1.7 million women receiving diagnoses annually, this translates into 120 000-460 000 women receiving neoadjuvant chemotherapy worldwide.1 Although data indicate that the first rationale remains valid, the others have not led to the desired outcomes. More conservative surgery after neoadjuvant chemotherapy can result in a higher rate of local recurrence, and, despite the earlier initiation of systemic treatment, no improvement in survival has been seen.234 Furthermore, neoadjuvant chemotherapy may not help test novel chemotherapies—although primary tumour response is a good indicator of prognosis for a particular treatment, it is counterintuitively a poor surrogate marker for the overall survival benefit when evaluating novel chemotherapy regimens. Finally, for 40-80% of patients, even the best neoadjuvant chemotherapy regimens extend the period the cancer remains in the breast and can make surgery more difficult, as the tumour is less easily palpable and the axillary lymph nodes are less distinct. We question the wisdom of the current widespread use of neoadjuvant chemotherapy

Building capacity for clinical research in developing countries: the INDOX cancer research network experience

Transnational Organisations increasingly prioritise the need to support local research capacity in low and middle income countries in order that local priorities are addressed with due consideration of contextual issues. There remains limited evidence on the best way in which this should be done or the ways in which external agencies can support this process

Pancreatitis following liver transplantation

Since 1981, when the liver transplantation program was initiated at the University of Pittsburgh, we have been impressed with the prevalence of pancreatitis occurring following liver transplantation in patients transplanted for hepatitis B—related liver disease. To either confirm this clinical impression or refute it, the records of the 27 HbsAg+ patients and those of an additional 24 HbsAg“but HbcAb and/or HbsAb+ patients who underwent orthotopic liver transplantation were reviewed to determine the prevalence of clinical pancreatitis and hyperamylasemia (biochemical pancreatitis) following liver transplantation (OLTx). Post-OLTx hyperamylasemia occurred significantly more frequently in HbsAg+ patients (6/27) than it did in the HbsAg- patients (0/24) (P<0.05). More importantly, clinical pancreatitis occurred in 14% (4/27) of the HbsAg+ patients and 0% (0/24) of the HbsAg- patients. Interestingly, in each case, the pancreatitis was associated with the occurrence of acute hepatitis B infection of the allograft. Based upon these data, we conclude that pancreatitis occurring after liver transplantation is more common in patients transplanted for active viral liver disease caused by hepatitis B than in those with inactive viral liver disease. These observations suggest that pancreatitis occurring in, at least some cases following liver transplantation for viral liver disease, may result from hepatitis B virus infection of the pancreas. © 1988 by The Williams and Wilkins Co

Abundance and local-scale processes contribute to multi-phyla gradients in global marine diversity

Among themost enduring ecological challenges is an integrated theory explaining the latitudinal biodiversity gradient, including discrepancies observed at different spatial scales. Analysis of Reef Life Survey data for 4127 marine species at 2406 coral and rocky sites worldwide confirms that the total ecoregion richness peaks in low latitudes, near +15 degrees N and -15 degrees S. However, although richness at survey sites is maximal near the equator for vertebrates, it peaks at high latitudes for large mobile invertebrates. Site richness for different groups is dependent on abundance, which is in turn correlated with temperature for fishes and nutrients for macroinvertebrates. We suggest that temperature-mediated fish predation and herbivory have constrained mobile macroinvertebrate diversity at the site scale across the tropics. Conversely, at the ecoregion scale, richness responds positively to coral reef area, highlighting potentially huge global biodiversity losses with coral decline. Improved conservation outcomes require management frameworks, informed by hierarchical monitoring, that cover differing site- and regional-scale processes across diverse taxa, including attention to invertebrate species, which appear disproportionately threatened by warming seas

Characterising Wildlife Trade Market Supply-Demand Dynamics.

The trade in wildlife products can represent an important source of income for poor people, but also threaten wildlife locally, regionally and internationally. Bushmeat provides livelihoods for hunters, traders and sellers, protein to rural and urban consumers, and has depleted the populations of many tropical forest species. Management interventions can be targeted towards the consumers or suppliers of wildlife products. There has been a general assumption in the bushmeat literature that the urban trade is driven by consumer demand with hunters simply fulfilling this demand. Using the urban bushmeat trade in the city of Kumasi, Ghana, as a case study, we use a range of datasets to explore the processes driving the urban bushmeat trade. We characterise the nature of supply and demand by explicitly considering three market attributes: resource condition, hunter behaviour, and consumer behaviour. Our results suggest that bushmeat resources around Kumasi are becoming increasingly depleted and are unable to meet demand, that hunters move in and out of the trade independently of price signals generated by the market, and that, for the Kumasi bushmeat system, consumption levels are driven not by consumer choice but by shortfalls in supply and consequent price responses. Together, these results indicate that supply-side processes dominate the urban bushmeat trade in Kumasi. This suggests that future management interventions should focus on changing hunter behaviour, although complementary interventions targeting consumer demand are also likely to be necessary in the long term. Our approach represents a structured and repeatable method to assessing market dynamics in information-poor systems. The findings serve as a caution against assuming that wildlife markets are demand driven, and highlight the value of characterising market dynamics to inform appropriate management

A Multi-Study Model-Based Evaluation of the Sequence of Imaging and Clinical Biomarker Changes in Huntington's Disease

Understanding the order and progression of change in biomarkers of neurodegeneration is essential to detect the effects of pharmacological interventions on these biomarkers. In Huntington’s disease (HD), motor, cognitive and MRI biomarkers are currently used in clinical trials of drug efficacy. Here for the first time we use directly compare data from three large observational studies of HD (total N = 532) using a probabilistic event-based model (EBM) to characterise the order in which motor, cognitive and MRI biomarkers become abnormal. We also investigate the impact of the genetic cause of HD, cytosine-adenine-guanine (CAG) repeat length, on progression through these stages. We find that EBM uncovers a broadly consistent order of events across all three studies; that EBM stage reflects clinical stage; and that EBM stage is related to age and genetic burden. Our findings indicate that measures of subcortical and white matter volume become abnormal prior to clinical and cognitive biomarkers. Importantly, CAG repeat length has a large impact on the timing of onset of each stage and progression through the stages, with a longer repeat length resulting in earlier onset and faster progression. Our results can be used to help design clinical trials of treatments for Huntington’s disease, influencing the choice of biomarkers and the recruitment of participants

A Graph-Based Semantics Workbench for Concurrent Asynchronous Programs

A number of novel programming languages and libraries have been proposed that offer simpler-to-use models of concurrency than threads. It is challenging, however, to devise execution models that successfully realise their abstractions without forfeiting performance or introducing unintended behaviours. This is exemplified by SCOOP---a concurrent object-oriented message-passing language---which has seen multiple semantics proposed and implemented over its evolution. We propose a "semantics workbench" with fully and semi-automatic tools for SCOOP, that can be used to analyse and compare programs with respect to different execution models. We demonstrate its use in checking the consistency of semantics by applying it to a set of representative programs, and highlighting a deadlock-related discrepancy between the principal execution models of the language. Our workbench is based on a modular and parameterisable graph transformation semantics implemented in the GROOVE tool. We discuss how graph transformations are leveraged to atomically model intricate language abstractions, and how the visual yet algebraic nature of the model can be used to ascertain soundness.Comment: Accepted for publication in the proceedings of FASE 2016 (to appear

Hepatic encephalopathy: current challenges and future prospects.

Hepatic encephalopathy (HE) is a common complication of liver dysfunction, including acute liver failure and liver cirrhosis. HE presents as a spectrum of neuropsychiatric symptoms ranging from subtle fluctuating cognitive impairment to coma. It is a significant contributor of morbidity in patients with liver disease. HE is observed in acute liver failure, liver bypass procedures, for example, shunt surgry and transjugular intrahepatic portosystemic shunt, and cirrhosis. These are classified as Type A, B and C HE, respectively. HE can also be classified according to whether its presence is overt or covert. The pathogenesis is linked with ammonia and glutamine production, and treatment is based on mechanisms to reduce the formation and/or removal of these compounds. There is no specific diagnostic test for HE, and diagnosis is based on clinical suspicion, excluding other causes and use of clinical tests that may support its diagnosis. Many tests are used in trials and experimentally, but have not yet gained universal acceptance. This review focuses on the definitions, pathogenesis and treatment of HE. Consideration will be given to existing treatment, including avoidance of precipitating factors and novel therapies such as prebiotics, probiotics, antibiotics, laxatives, branched-chain amino acids, shunt embolization and the importance of considering liver transplant in appropriate cases