Nonsurgical Approaches to Treat Biliary Tract and Liver Tumors

Endoscopic and percutaneous therapies have been shown to prolong life and reduce morbidity for patients with unresectable advanced stages of primary hepatobiliary malignancies. This article reviews pertinent studies published within the last 5 years that involve locoregional techniques to manage hepatocellular carcinoma, perihilar and distal cholangiocarcinoma. A major emphasis is placed on photodynamic therapy, radiofrequency ablation, irreversible electroporation, and microwave ablation. Technical advances, combinational therapies, and postintervention outcomes are discussed. Despite widespread application, high-quality evidence does not show superiority of any particular locoregional technique for treating advanced hepatobiliary cancers

From Markovian to pairwise epidemic models and the performance of moment closure approximations

Many if not all models of disease transmission on networks can be linked to the exact state-based Markovian formulation. However the large number of equations for any system of realistic size limits their applicability to small populations. As a result, most modelling work relies on simulation and pairwise models. In this paper, for a simple SIS dynamics on an arbitrary network, we formalise the link between a well known pairwise model and the exact Markovian formulation. This involves the rigorous derivation of the exact ODE model at the level of pairs in terms of the expected number of pairs and triples. The exact system is then closed using two different closures, one well established and one that has been recently proposed. A new interpretation of both closures is presented, which explains several of their previously observed properties. The closed dynamical systems are solved numerically and the results are compared to output from individual-based stochastic simulations. This is done for a range of networks with the same average degree and clustering coefficient but generated using different algorithms. It is shown that the ability of the pairwise system to accurately model an epidemic is fundamentally dependent on the underlying large-scale network structure. We show that the existing pairwise models are a good fit for certain types of network but have to be used with caution as higher-order network structures may compromise their effectiveness

The potential for income and employment generation in Kenya's urban informal sector: a proposed survey

This paper is concerned with a survey of informal sector enterprises that the authors propose to carry out in Nairobi this year. The emphasis is placed on the search for more information on the operation of the sector's enterprises, particularly their constraints on expansion, so that policies of help and encouragement can be formulated from a more informed data base

Beyond clustering: mean-field dynamics on networks with arbitrary subgraph composition

Clustering is the propensity of nodes that share a common neighbour to be connected. It is ubiquitous in many networks but poses many modelling challenges. Clustering typically manifests itself by a higher than expected frequency of triangles, and this has led to the principle of constructing networks from such building blocks. This approach has been generalised to networks being constructed from a set of more exotic subgraphs. As long as these are fully connected, it is then possible to derive mean-field models that approximate epidemic dynamics well. However, there are virtually no results for non-fully connected subgraphs. In this paper, we provide a general and automated approach to deriving a set of ordinary differential equations, or mean-field model, that describes, to a high degree of accuracy, the expected values of system-level quantities, such as the prevalence of infection. Our approach offers a previously unattainable degree of control over the arrangement of subgraphs and network characteristics such as classical node degree, variance and clustering. The combination of these features makes it possible to generate families of networks with different subgraph compositions while keeping classical network metrics constant. Using our approach, we show that higher-order structure realised either through the introduction of loops of different sizes or by generating networks based on different subgraphs but with identical degree distribution and clustering, leads to non-negligible differences in epidemic dynamics

Evaluation of milk yield losses associated with Salmonella antibodies in bulk-tank milk in bovine dairy herds

The effect of Salmonella on milk production is not well established in cattle. The objective of this study was to investigate whether introduction of Salmonella into dairy cattle herds was associated with reduced milk yield and the duration of any effect. Longitudinal data from 2005 through 2009 were used, with data from 12 months before until 18 months after the estimated date of infection. Twenty-eight case herds were selected based on an increase in the level of Salmonella specific antibodies in bulk-tank milk from < 10 corrected optic density percentage (ODC%) to ≥ 70 ODC% between two consecutive 3-monthly measurements in the Danish Salmonella surveillance program. All selected case herds were conventional Danish Holstein herds. Control herds (n = 40) were selected randomly from Danish Holstein herds with Salmonella antibody levels consistently < 10 ODC%. A date of herd infection was randomly allocated to the control herds. Hierarchical mixed effect models with the outcome test day energy corrected milk yield (ECM)/cow were used to investigate the daily milk yield before and after the estimated herd infection date for cows in parity 1, 2 and 3+. Control herds were used to evaluate whether the effects in the case herds could be reproduced in herds without Salmonella infection. Herd size, days in milk, somatic cell count, season, and year were included in the models. The key results were that first parity cow yield was reduced by a mean of 1.4 kg (95% CI: 0.5 to 2.3) ECM/cow per day from seven to 15 months after the estimated herd infection date, compared with first parity cows in the same herds in the 12 months before the estimated herd infection date. Yield for parity 3+ was reduced by a mean of 3.0 kg (95% CI: 1.3 to 4.8) ECM/cow per day from seven to 15 months after herd infection compared with parity 3+ cows in the 12 months before the estimated herd infection. There were minor differences in yield in second parity cows before and after herd infection, and no difference between cows in control herds before and after the simulated infection date. There was a significant drop in milk yield in affected herds and the reduction was detectable several months after the increase in bulk-tank milk Salmonella antibodies. It took more than a year for milk yield to return to pre- infection levels

Disseminated neoplasia in blue mussels, Mytilus galloprovincialis, from the Black Sea, Romania

Disseminated neoplasia, also called leukemia or hemic neoplasia, has been detected in 15 species of marine bivalve mollusks worldwide. The disease is characterized by the presence of single anaplastic cells with enlarged nuclei and sometimes frequent mitosis, in hemolymph vessels and sinuses. The neoplastic cells gradually replace normal hemocytes leading to the increased mortality of animals. The neoplasia reaches epizootic prevalences in blue mussels, Mytilus trossulus, in some areas, whereas prevalences in Mytilus edulis are generally very low. Mytilus galloprovincialis was suggested to be resistant to the disease although very low prevalences were documented from Spain in the Atlantic Ocean and Italy in the Mediterranean Sea. A case of disseminated neoplasia was discovered in M. galloprovincialis from among 200 specimens studied from the coast of the Romanian Black Sea. Histological preparation revealed the presence of large anaplastic cells with lobed nuclei. This observation extends the geographic range of marine bivalve mollusks with disseminated neoplasia to include the Black Sea

The impact of contact tracing in clustered populations

The tracing of potentially infectious contacts has become an important part of the control strategy for many infectious diseases, from early cases of novel infections to endemic sexually transmitted infections. Here, we make use of mathematical models to consider the case of partner notification for sexually transmitted infection, however these models are sufficiently simple to allow more general conclusions to be drawn. We show that, when contact network structure is considered in addition to contact tracing, standard “mass action” models are generally inadequate. To consider the impact of mutual contacts (specifically clustering) we develop an improvement to existing pairwise network models, which we use to demonstrate that ceteris paribus, clustering improves the efficacy of contact tracing for a large region of parameter space. This result is sometimes reversed, however, for the case of highly effective contact tracing. We also develop stochastic simulations for comparison, using simple re-wiring methods that allow the generation of appropriate comparator networks. In this way we contribute to the general theory of network-based interventions against infectious disease

Constraining the long-term evolution of the slip rate for a major extensional fault system in the central Aegean, Greece, using thermochronology

The brittle/ductile transition is a major rheologic boundary in the crust yet little is known about how or if rates of tectonic processes are influenced by this boundary. In this study we examine the slip history of the large-scale Naxos/Paros extensional fault system (NPEFS), Cyclades, Greece, by comparing published slip rates for the ductile crust with new thermochronological constraints on slip rates in the brittle regime. Based on apatite and zircon fission-track (AFT and ZFT) and (U–Th)/He dating we observe variable slip rates across the brittle/ductile transition on Naxos. ZFT and AFT ages range from 11.8 ± 0.8 to 9.7 ± 0.8 Ma and 11.2 ± 1.6 to 8.2 ± 1.2 Ma and (U–Th)/He zircon and apatite ages are between 10.4 ± 0.4 to 9.2 ± 0.3 Ma and 10.7 ± 1.0 to 8.9 ± 0.6 Ma, respectively. On Paros, ZFT and AFT ages range from 13.1 ± 1.4 Ma to 11.1 ± 1.0 Ma and 12.7 ± 2.8 Ma to 10.5 ± 2.0 Ma while the (U–Th)/He zircon ages are slightly younger between 8.3 ± 0.4 Ma and 9.8 ± 0.3 Ma. All ages consistently decrease northwards in the direction of hanging wall transport. Most of our new thermochronological results and associated thermal modeling more strongly support the scenario of an identical fault dip and a constant or slightly accelerating slip rate of 6–8 km Myr− 1 on the NPEFS across the brittle/ductile transition. Even the intrusion of a large granodiorite body into the narrowing fault zone at 12 Ma on Naxos does not seem to have affected the thermal structure of the area in a way that would significantly disturb the slip rate. The data also show that the NPEFS accomplished a minimum total offset of 50 km between 16 and 8 Ma

Patterns of ^(15)N assimilation and growth of methanotrophic ANME-2 archaea and sulfate-reducing bacteria within structured syntrophic consortia revealed by FISH-SIMS

Methane release from the oceans is controlled in large part by syntrophic interactions between anaerobic methanotrophic archaea (ANME) and sulfate-reducing bacteria (DSS), frequently found as organized consortia. An understanding of the specifics of this symbiotic relationship and the metabolic heterogeneity existing between and within individual methane-oxidizing aggregates is currently lacking. Here, we use the microanalytical method FISH-SIMS (fluorescence in situ hybridization-secondary ion mass spectrometry) to describe the physiological traits and anabolic activity of individual methanotrophic consortia, specifically tracking ^(15)N-labelled protein synthesis to examine the effects of organization and size on the metabolic activity of the syntrophic partners. Patterns of 15N distribution within individual aggregates showed enhanced ^(15)N assimilation in ANME-2 cells relative to the co-associated DSS revealing a decoupling in anabolic activity between the partners. Protein synthesis in ANME-2 cells was sustained throughout the core of individual ANME-2/DSS consortia ranging in size range from 4 to 20 μm. This indicates that metabolic activity of the methane-oxidizing archaea is not limited to, or noticeably enhanced at the ANME−2/DSS boundary. Overall, the metabolic activity of both syntrophic partners within consortia was greater than activity measured in representatives of the ANME-2 and DSS observed alone, with smaller ANME-2/DSS aggregates displaying a tendency for greater ^(15)N uptake and doubling times ranging from 3 to 5 months. The combination of ^(15)N-labelling and FISH-SIMS provides an important perspective on the extent of heterogeneity within methanotrophic aggregates and may aid in constraining predictive models of activity and growth by these syntrophic consortia

Longer-term effectiveness of systemic family therapy compared with treatment as usual for young people after self-harm: An extended follow up of pragmatic randomised controlled trial

Background: Self-harm in adolescents is common and repetition frequent. Evidence for effective interventions to reduce self-harm is limited. Long term follow-up of existing studies is rare. Methods: Extended follow up, from 18 to at least 36-months, of the SHIFT trial: a pragmatic, multi-centre, individually-randomised, controlled trial involving young people (11–17) who had self-harmed at least twice and presented to Child & Adolescent Mental Health Services (CAMHS). SHIFT evaluated manualised family therapy (FT) versus treatment as usual (TAU) in reducing repetition of self-harm leading to hospital attendance 18 months post-randomisation. We obtained ONS mortality data, adult mental health data, and further details of hospital attendance from routine Hospital Episode Statistics (HES) data plus researcher follow-up. We assessed longer-term differences in outcome using multivariable Cox Proportional Hazards regression analysis, and assessed all-cause mortality and morbidity relating to hospital attendances for reasons other than self-harm. Study registration: ISRCTN 59793150 Outcomes: The original sample of 832 were randomised between April 2010 and December 2013. Extended follow-up continued until February 2017 for a median 55·4 months (range 0–82·5 months), providing post 18-month data for 804 (96·6%) participants, of whom 785 (94·4%) had a minimum of 36-months follow-up. There was no evidence of a between-group difference in the primary outcome during the extended follow-up period (Hazard Ratio (HR) 1·03; 95% CI: 0·83, 1·28; p-value=0·78), consistent with our findings in the original trial with 18 months follow-up (HR 1·14, 95% CI 0·87, 1·49; p-value 0·33). There was a reduced rate of self-harm in older participants aged 15–17 (HR 0·7, 95% CI 0·56, 0·88), as compared with those aged 11–14; and significantly increased rates of self-harm in participants whose index episode combined self-injury and poisoning (HR 1·8, 95% CI 1·2, 2·7). Two deaths were reported during the extended follow up period. Interpretation: For adolescents referred to CAMHS after self-harm, having self-harmed at least once before, trial FT confers no benefits over TAU in reducing subsequent hospitalisation for self-harm over 18 months or 36 months. Funding: NIHR HTA Reference: 07/33/0