Measuring Infringement of Intellectual Property Rights

© Crown Copyright 2014. You may re-use this information (excluding logos) free of charge in any format or medium, under the terms of the Open Government Licence. To view this licence, visit http://www.nationalarchives.gov. uk/doc/open-government-licence/ Where we have identified any third party copyright information you will need to obtain permission from the copyright holders concernedThe review is wide-ranging in scope and overall our findings evidence a lack of appreciation among those producing research for the high-level principles of measurement and assessment of scale. To date, the approaches adopted by industry seem more designed for internal consumption and are usually contingent on particular technologies and/or sector perspectives. Typically, there is a lack of transparency in the methodologies and data used to form the basis of claims, making much of this an unreliable basis for policy formulation. The research approaches we found are characterised by a number of features that can be summarised as a preference for reactive approaches that look to establish snapshots of an important issue at the time of investigation. Most studies are ad hoc in nature and on the whole we found a lack of sustained longitudinal approaches that would develop the appreciation of change. Typically the studies are designed to address specific hypotheses that might serve to support the position of the particular commissioning body. To help bring some structure to this area, we propose a framework for the assessment of the volume of infringement in each different area. The underlying aim is to draw out a common approach wherever possible in each area, rather than being drawn initially to the differences in each field. We advocate on-going survey tracking of the attitudes, perceptions and, where practical, behaviours of both perpetrators and claimants in IP infringement. Clearly, the nature of perpetrators, claimants and enforcement differs within each IPR but in our view the assessment for each IPR should include all of these elements. It is important to clarify that the key element of the survey structure is the adoption of a survey sampling methodology and smaller volumes of representative participation. Once selection is given the appropriate priority, a traditional offline survey will have a part to play, but as the opportunity arises, new technological methodologies, particularly for the voluntary monitoring of online behaviour, can add additional detail to the overall assessment of the scale of activity. This framework can be applied within each of the IP right sectors: copyright, trademarks,patents, and design rights. It may well be that the costs involved with this common approach could be mitigated by a syndicated approach to the survey elements. Indeed, a syndicated approach has a number of advantages in addition to cost. It could be designed to reduce any tendency either to hide inappropriate/illegal activity or alternatively exaggerate its volume to fit with the theme of the survey. It also has the scope to allow for monthly assessments of attitudes rather than being vulnerable to unmeasured seasonal impacts

Loss of locus coeruleus noradrenergic neurons alters the inflammatory response to LPS in substantia nigra but does not affect nigral cell loss

This is the accepted version of the following article: Mahmoud M. Iravani, Mona Sadeghian, Sarah Rose and Peter Jenner, “Loss of locus coeruleus noradrenergic neurons alters the inflammatory response to LPS in substantia nigra but does not affect nigral cell loss”, Journal of Neural Transmission, Vol. 121(12): 1493-1505, first published online 30 April 2014. The version of record is available online via doi: 10.1007/s00702-014-1223-1. © Springer-Verlag Wien 2014In Parkinson's disease (PD), destruction of noradrenergic neurons in the locus coeruleus (LC) may precede damage to nigral cells and subsequently exaggerate dopaminergic cell loss. We examine if destruction of the locus coeruleus with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) alters dopaminergic cell loss in substantia nigra (SN) initiated by lipopolysaccharide (LPS) in the rat through an effect on glial cell activation. In rats, a single intraperitoneal dose of DSP-4 administered 8 days previously, caused a marked loss of tyrosine hydroxylase positive neurons in LC but no change in dopaminergic cell number in SN. Unilateral nigral LPS administration resulted in marked dopaminergic cell death with reactive microgliosis associated with enhanced p47 phox in OX-6 and OX-42 positive microglia. There was proliferation of inducible nitric oxide synthase (iNOS)-positive cells, formation of 3-nitrotyrosine (3-NT) and proliferation of astrocytes that expressed glial cell line-derived neurotrophic factor (GDNF). Following combined DSP-4 treatment and subsequent administration of LPS, unexpectedly, no further loss of tyrosine hydroxylase (TH)-immunoreactivity (-ir) occurred in the SN compared to the effects of LPS alone. However, there was a marked alteration in the morphology of microglial cell and a reduction of 3-NT- and iNOS-ir was evident. Expression of p47 phox was downregulated in microglia but up-regulated in TH-ir neurons. No further change in GFAP-ir was observed compared to that produced by DSP-4 alone or LPS alone, but the expression of GDNF was markedly reduced. This study suggests that in contrast to previous reports, prior LC damage does not influence subsequent nigral dopaminergic cell degeneration induced by LPS. Rather it appears to attenuate the microglial response thought to contribute to disease progression in PD.Peer reviewedFinal Accepted Versio

Mathematical modelling of the interaction between cancer cells and an oncolytic virus: insights into the effects of treatment protocols

Oncolytic virotherapy is an experimental cancer treatment that uses genetically engineered viruses to target and kill cancer cells. One major limitation of this treatment is that virus particles are rapidly cleared by the immune system, preventing them from arriving at the tumour site. To improve virus survival and infectivity modified virus particles with the polymer polyethylene glycol (PEG) and the monoclonal antibody herceptin. While PEG modification appeared to improve plasma retention and initial infectivity it also increased the virus particle arrival time. We derive a mathematical model that describes the interaction between tumour cells and an oncolytic virus. We tune our model to represent the experimental data by Kim et al. (2011) and obtain optimised parameters. Our model provides a platform from which predictions may be made about the response of cancer growth to other treatment protocols beyond those in the experiments. Through model simulations we find that the treatment protocol affects the outcome dramatically. We quantify the effects of dosage strategy as a function of tumour cell replication and tumour carrying capacity on the outcome of oncolytic virotherapy as a treatment. The relative significance of the modification of the virus and the crucial role it plays in optimising treatment efficacy is explored.Comment: 15 pages, 6 figure

Mining Medical Data: Bridging the Knowledge Divide

Due to the signi¯cant amount of data generated by modern medicine there is a growing reliance on tools such as data mining and knowledge discovery to help make sense and comprehend such data. The success of this process requires collaboration and interaction between such methods and medical professionals. Therefore an important question is: How can we strengthen the relationship between two traditionally separate fields (technology and medicine) in order to work simultaneously towards enhancing knowledge in modern medicine. To address this question, this study examines the application of data mining techniques to a large asthma medical dataset. A discussion introducing various methods for a smooth approach, straying from the `jack of all trades, master of none' to a modular cooperative approach for a successful outcome is pro-posed. The results of this study support the use of data mining as a useful tool and highlight the advantages on a global scale of closer relations between the two distinct fields. The exploration of CRISP methodology suggests that a `one methodology fits all approach' is not appropriate, but rather combines to create a hybrid holistic approach to data mining

Widespread tephra dispersal and ignimbrite emplacement from a subglacial volcano (Torfajökull, Iceland)

The tephra dispersal mechanisms of rhyolitic glaciovolcanic eruptions are little known, but can be investigated through the correlation of eruptive products across multiple depositional settings. Using geochemistry and geochronology, we correlate a regionally important Pleistocene tephra horizon—the rhyolitic component of North Atlantic Ash Zone II (II-RHY-1)—and the Thórsmörk Ignimbrite with rhyolitic tuyas at Torfajökull volcano, Iceland. The eruption breached an ice mass >400 m thick, leading to the widespread dispersal of II-RHY-1 across the North Atlantic and the Greenland ice sheet. Locally, pyroclastic density currents traveled across the ice surface, depositing the variably welded Thórsmörk Ignimbrite beyond the ice margin and ~30 km from source. The widely dispersed products of this eruption represent a valuable isochronous tie line between terrestrial, marine, and ice-core paleoenvironmental records. Using the tephra horizon, estimates of ice thickness and extent derived from the eruption deposits can be directly linked to the regional climate archive, which records the eruption at the onset of Greenland Stadial 15.2

Stratification of the phase clouds and statistical effects of the non-Markovity in chaotic time series of human gait for healthy people and Parkinson patients

In this work we develop a new method of diagnosing the nervous system diseases and a new approach in studying human gait dynamics with the help of the theory of discrete non-Markov random processes. The stratification of the phase clouds and the statistical non-Markov effects in the time series of the dynamics of human gait are considered. We carried out the comparative analysis of the data of four age groups of healthy people: children (from 3 to 10 year olds), teenagers (from 11 to 14 year oulds), young people (from 21 up to 29 year oulds), elderly persons (from 71 to 77 year olds) and Parkinson patients. The full data set are analyzed with the help of the phase portraits of the four dynamic variables, the power spectra of the initial time correlation function and the memory functions of junior orders, the three first points in the spectra of the statistical non-Markov parameter. The received results allow to define the predisposition of the probationers to deflections in the central nervous system caused by Parkinson's disease. We have found out distinct differencies between the five submitted groups. On this basis we offer a new method of diagnostics and forecasting Parkinson's disease.Comment: 15 pages, 5 figs, 3 Table

Чергове засідання Ради Міжнародної асоціації академій наук

7 червня 2012 року в Національному дослідницькому центрі «Курчатовський інститут» відбулося чергове засідання Ради Міжнародної асоціації академій наук (МААН). Під час урочистої церемонії закриття засідання президенту МААН, президенту НАН України академіку НАН України і РАН Борису Євгеновичу Патону було присвоєно звання Почесного доктора НДЦ «Курчатовський інститут»

Subacute administration of both methcathinone and manganese causes basal ganglia damage in mice resembling that in methcathinone abusers

An irreversible extrapyramidal syndrome occurs in man after intravenous abuse of "homemade" methcathinone (ephedrone, Mcat) that is contaminated with manganese (Mn) and is accompanied by altered basal ganglia function. Both Mcat and Mn can cause alterations in nigrostriatal function but it remains unknown whether the effects of the 'homemade' drug seen in man are due to Mcat or to Mn or to a combination of both. To determine how toxicity occurs, we have investigated the effects of 4-week intraperitoneal administration of Mn (30 mg/kg t.i.d) and Mcat (100 mg/kg t.i.d.) given alone, on the nigrostriatal function in male C57BL6 mice. The effects were compared to those of the 'homemade' mixture which contained about 7 mg/kg of Mn and 100 mg/kg of Mcat. Motor function, nigral dopaminergic cell number and markers of pre- and postsynaptic dopaminergic neuronal integrity including SPECT analysis were assessed. All three treatments had similar effects on motor behavior and neuronal markers. All decreased motor activity and induced tyrosine hydroxylase positive cell loss in the substantia nigra. All reduced I-123-epidepride binding to D2 receptors in the striatum. Vesicular monoamine transporter 2 (VMAT2) binding was not altered by any drug treatment. However, Mcat treatment alone decreased levels of the dopamine transporter (DAT) and Mn alone reduced GAD immunoreactivity in the striatum. These data suggest that both Mcat and Mn alone could contribute to the neuronal damage caused by the 'homemade' mixture but that both produce additional changes that contribute to the extrapyramidal syndrome seen in man.Peer reviewe

Cyclin-dependent kinase 9 as a potential target for anti-TNF resistant inflammatory bowel disease

BACKGROUND AND AIMS: Resistance to single cytokine blockade, namely anti-TNF therapy, is a growing concern for patients with inflammatory bowel disease (IBD). The transcription factor T-bet is a critical regulator of intestinal homeostasis, is genetically linked to mucosal inflammation and controls the expression of multiples genes such as the pro-inflammatory cytokines IFN-γ and TNF. Inhibiting T-bet may therefore offer a more attractive prospect for treating IBD but remains challenging to target therapeutically. In this study, we evaluate the effect of targeting the transactivation function of T-bet using inhibitors of P-TEFb (CDK9-cyclin T), a transcriptional elongation factor downstream of T-bet. METHODS: Using an adaptive immune-mediated colitis model, human colonic lymphocytes from IBD patients and multiple large clinical datasets, we investigate the effect of CDK9 inhibitors on cytokine production and gene expression in colonic CD4+ T cells and link these genetic modules to clinical response in patients with IBD. RESULTS: Systemic CDK9 inhibition led to histological improvement of immune-mediated colitis and was associated with targeted suppression of colonic CD4+ T cell-derived IFN-γ and IL-17A. In colonic lymphocytes from IBD patients, CDK9 inhibition potently repressed genes responsible for pro-inflammatory signalling, and in particular genes regulated by T-bet. Remarkably, CDK9 inhibition targeted genes that were highly expressed in anti-TNF resistant IBD and that predicted non-response to anti-TNF therapy. CONCLUSION: Collectively, our findings reveal CDK9 as a potential target for anti-TNF resistant IBD, which has the potential for rapid translation to the clinic