Exploring pig trade patterns to inform the design of risk-based disease surveillance and control strategies

An understanding of the patterns of animal contact networks provides essential information for the design of risk-based animal disease surveillance and control strategies. This study characterises pig movements throughout England and Wales between 2009 and 2013 with a view to characterising spatial and temporal patterns, network topology and trade communities. Data were extracted from the Animal and Plant Health Agency (APHA)’s RADAR (Rapid Analysis and Detection of Animal-related Risks) database, and analysed using descriptive and network approaches. A total of 61,937,855 pigs were moved through 872,493 movements of batches in England and Wales during the 5-year study period. Results show that the network exhibited scale-free and small-world topologies, indicating the potential for diseases to quickly spread within the pig industry. The findings also provide suggestions for how risk-based surveillance strategies could be optimised in the country by taking account of highly connected holdings, geographical regions and time periods with the greatest number of movements and pigs moved, as these are likely to be at higher risk for disease introduction. This study is also the first attempt to identify trade communities in the country, information which could be used to facilitate the pig trade and maintain disease-free status across the country in the event of an outbreak

Endothelial-Mesenchymal Transition of Brain Endothelial Cells: Possible Role during Metastatic Extravasation

Cancer progression towards metastasis follows a defined sequence of events described as the metastatic cascade. For extravasation and transendothelial migration metastatic cells interact first with endothelial cells. Yet the role of endothelial cells during the process of metastasis formation and extravasation is still unclear, and the interaction between metastatic and endothelial cells during transendothelial migration is poorly understood. Since tumor cells are well known to express TGF-beta, and the compact endothelial layer undergoes a series of changes during metastatic extravasation (cell contact disruption, cytoskeletal reorganization, enhanced contractility), we hypothesized that an EndMT may be necessary for metastatic extravasation. We demonstrate that primary cultured rat brain endothelial cells (BEC) undergo EndMT upon TGF-beta 1 treatment, characterized by the loss of tight and adherens junction proteins, expression of fibronectin, beta 1-integrin, calponin and a-smooth muscle actin (SMA). B16/F10 cell line conditioned and activated medium (ACM) had similar effects: claudin-5 down-regulation, fibronectin and SMA expression. Inhibition of TGF-beta signaling during B16/F10 ACM stimulation using SB-431542 maintained claudin-5 levels and mitigated fibronectin and SMA expression. B16/F10 ACM stimulation of BECs led to phosphorylation of Smad2 and Smad3. SB-431542 prevented SMA up-regulation upon stimulation of BECs with A2058, MCF-7 and MDA-MB231 ACM as well. Moreover, B16/F10 ACM caused a reduction in trans-endothelial electrical resistance, enhanced the number of melanoma cells adhering to and transmigrating through the endothelial layer, in a TGF-beta-dependent manner. These effects were not confined to BECs: HUVECs showed TGF-beta-dependent SMA expression when stimulated with breast cancer cell line ACM. Our results indicate that an EndMT may be necessary for metastatic transendothelial migration, and this transition may be one of the potential mechanisms occurring during the complex phenomenon known as metastatic extravasation

GSK-3 Activity Is Critical for the Orientation of the Cortical Microtubules and the Dorsoventral Axis Determination in Zebrafish Embryos

The formation of dorsal-ventral (D–V) axis is the earliest event that breaks the radial symmetry and determines the bilateral body plan of a vertebrate embryo, however, the maternal control of this process is not fully understood. Here, we discovered a new dorsalizing window of acute lithium treatment, which covers only less than 10 minutes after fertilization. Lithium treatment in this window was not able to reverse the ventralized phenotype in tokkeabi (tkk) mutant embryos, and its dorsalizing activity on wild-type embryos was inhibited by nocodazole co-treatment. These evidences indicate that the underlying mechanism is independent of a direct activation of Wnt/β-catenin signaling, but depends on the upstream level of the microtubule mediated dorsal determinant transport. In order to identify the target of lithium in this newly discovered sensitive window, GSK-3 inhibitor IX as well as the IMPase inhibitor L690, 330 treatments were performed. We found that only GSK-3 inhibitor IX treatment mimicked the lithium treatment in the dorsalizing activity. Further study showed that the parallel pattern of cortical microtubules in the vegetal pole region and the directed migration of the Wnt8a mRNA were randomized by either lithium or GSK-3 inhibitor IX treatment. These results thus revealed an early and critical role of GSK-3 activity that regulates the orientation of the cortical microtubules and the directed transport of the dorsal determinants in zebrafish embryos

Genetic polymorphisms of cytochrome P4501A1 and oesophageal squamous-cell carcinoma in Taiwan

Several in vitro studies have demonstrated that genetic polymorphisms result in functionally significant changes in cytochrome p4501A1 (either CYP1A1 MspI or exon 7) but the few epidemiologic studies of these polymorphisms in oesophageal squamous-cell carcinoma have been inconclusive. These inconclusive results motivated us to further examine the relationship between CYP1A1 MspI and exon 7 polymorphisms and risk of oesophageal cancer. In total, 146 cases of oesophageal squamous-cell-carcinoma and 324 control cases (a total of 470 cases) were genotyped from records at three Taiwan hospitals. No significant association was noted for the CYP1A1 MspI polymorphism variable between carcinoma and control cases. In contrast, the frequency of Ile/Ile, Ile/Val, and Val/Val in exon 7 was 68 (46.6%), 62 (42.5%), and 16 (11.0%) in carcinoma cases and 179 (55.3%), 127 (39.2%), and 18 (5.6%) in control cases, respectively. After factoring out other potential contributing factors, patients with Val/Val showed a 2.48 (95% CT=1.15–5.34) greater risk of developing oesophageal cancer than those with Ile/Ile. A slightly (albeit not significantly) greater risk was identified in subjects with Ile/Val (OR=1.34; 95% CI=0.86–2.07). These findings suggest that an exon 7 polymorphism, not a MspI polymorphism, in CYP1A1 may be pivotal in the development of oesophageal cancer

Controlling epidemic spread by social distancing: Do it well or not at all

BACKGROUND: Existing epidemiological models have largely tended to neglect the impact of individual behaviour on the dynamics of diseases. However, awareness of the presence of illness can cause people to change their behaviour by, for example, staying at home and avoiding social contacts. Such changes can be used to control epidemics but they exact an economic cost. Our aim is to study the costs and benefits of using individual-based social distancing undertaken by healthy individuals as a form of control.METHODS: Our model is a standard SIR model superimposed on a spatial network, without and with addition of small-world interactions. Disease spread is controlled by allowing susceptible individuals to temporarily reduce their social contacts in response to the presence of infection within their local neighbourhood. We ascribe an economic cost to the loss of social contacts, and weigh this against the economic benefit gained by reducing the impact of the epidemic. We study the sensitivity of the results to two key parameters, the individuals' attitude to risk and the size of the awareness neighbourhood.RESULTS: Depending on the characteristics of the epidemic and on the relative economic importance of making contacts versus avoiding infection, the optimal control is one of two extremes: either to adopt a highly cautious control, thereby suppressing the epidemic quickly by drastically reducing contacts as soon as disease is detected; or else to forego control and allow the epidemic to run its course. The worst outcome arises when control is attempted, but not cautiously enough to cause the epidemic to be suppressed. The next main result comes from comparing the size of the neighbourhood of which individuals are aware to that of the neighbourhood within which transmission can occur. The control works best when these sizes match and is particularly ineffective when the awareness neighbourhood is smaller than the infection neighbourhood. The results are robust with respect to inclusion of long-range, small-world links which destroy the spatial structure, regardless of whether individuals can or cannot control them. However, addition of many non-local links eventually makes control ineffective.CONCLUSIONS: These results have implications for the design of control strategies using social distancing: a control that is too weak or based upon inaccurate knowledge, may give a worse outcome than doing nothing

Search for new physics with same-sign isolated dilepton events with jets and missing transverse energy

A search for new physics is performed in events with two same-sign isolated leptons, hadronic jets, and missing transverse energy in the final state. The analysis is based on a data sample corresponding to an integrated luminosity of 4.98 inverse femtobarns produced in pp collisions at a center-of-mass energy of 7 TeV collected by the CMS experiment at the LHC. This constitutes a factor of 140 increase in integrated luminosity over previously published results. The observed yields agree with the standard model predictions and thus no evidence for new physics is found. The observations are used to set upper limits on possible new physics contributions and to constrain supersymmetric models. To facilitate the interpretation of the data in a broader range of new physics scenarios, information on the event selection, detector response, and efficiencies is provided.Comment: Published in Physical Review Letter

Azimuthal anisotropy of charged particles at high transverse momenta in PbPb collisions at sqrt(s[NN]) = 2.76 TeV

The azimuthal anisotropy of charged particles in PbPb collisions at nucleon-nucleon center-of-mass energy of 2.76 TeV is measured with the CMS detector at the LHC over an extended transverse momentum (pt) range up to approximately 60 GeV. The data cover both the low-pt region associated with hydrodynamic flow phenomena and the high-pt region where the anisotropies may reflect the path-length dependence of parton energy loss in the created medium. The anisotropy parameter (v2) of the particles is extracted by correlating charged tracks with respect to the event-plane reconstructed by using the energy deposited in forward-angle calorimeters. For the six bins of collision centrality studied, spanning the range of 0-60% most-central events, the observed v2 values are found to first increase with pt, reaching a maximum around pt = 3 GeV, and then to gradually decrease to almost zero, with the decline persisting up to at least pt = 40 GeV over the full centrality range measured.Comment: Replaced with published version. Added journal reference and DO

Compressed representation of a partially defined integer function over multiple arguments

In OLAP (OnLine Analitical Processing) data are analysed in an n-dimensional cube. The cube may be represented as a partially defined function over n arguments. Considering that often the function is not defined everywhere, we ask: is there a known way of representing the function or the points in which it is defined, in a more compact manner than the trivial one

Measurement of jet fragmentation into charged particles in pp and PbPb collisions at sqrt(s[NN]) = 2.76 TeV

Jet fragmentation in pp and PbPb collisions at a centre-of-mass energy of 2.76 TeV per nucleon pair was studied using data collected with the CMS detector at the LHC. Fragmentation functions are constructed using charged-particle tracks with transverse momenta pt > 4 GeV for dijet events with a leading jet of pt > 100 GeV. The fragmentation functions in PbPb events are compared to those in pp data as a function of collision centrality, as well as dijet-pt imbalance. Special emphasis is placed on the most central PbPb events including dijets with unbalanced momentum, indicative of energy loss of the hard scattered parent partons. The fragmentation patterns for both the leading and subleading jets in PbPb collisions agree with those seen in pp data at 2.76 TeV. The results provide evidence that, despite the large parton energy loss observed in PbPb collisions, the partition of the remaining momentum within the jet cone into high-pt particles is not strongly modified in comparison to that observed for jets in vacuum.Comment: Submitted to the Journal of High Energy Physic

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO