The 'ratione temporis' elements of self-defence

This article focuses on one particular factor that is of crucial importance to all self-defence actions. It is a factor that is almost always present in the application and appraisal of the right, but one that is not always explicitly engaged with: time. There are various ratione temporis elements underpinning the lawful exercise of the right of self-defence, and questions related to the timing of both an attack being responded to in self-defence and the response itself are notably controversial. The self-defence timeline is therefore charted, and the key legal debates encountered along its trajectory are identified. In particular, there is a focus on three temporal ‘stages’ of the right of self-defence: (i) the much-debated question of preventative forms of self-defence (the ‘before’); (ii) the timeliness of a state's defensive action, or what is sometimes called the need for the response to be ‘immediate’ (the ‘during’); and (iii) the duration of self-defence actions, including the crucial issue of when they must end (the ‘after’). The aim of this article is not to break new substantive ground with regard to these ‘stages’ as such, but is, rather, to draw together the temporal strands of self-defence in a more focused manner than is often the case in the literature.

The current status of anticoagulant resistance in rats and mice in the UK

Introduction: Resistance to anticoagulants in Norway rats (Rattus norvegicus) and house mice (Mus domesticus) has been studied in the UK since the early 1960s. In no other country in the world is our understanding of resistance phenomena so extensive and profound. Almost every aspect of resistance in the key rodent target species has been examined in laboratory and field trials and results obtained by independent researchers have been published. It is the principal purpose of this document to present a short synopsis of this information. More recently, however, the development of genetical techniques has provided a definitive means of detection of resistant genotypes among pest rodent populations. Preliminary information from a number of such surveys will also be presented. Resistance in Norway rats: A total of nine different anticoagulant resistance mutations (single nucleotide polymorphisms or SNPs) are found among Norway rats in the UK. In no other country worldwide are present so many different forms of Norway rat resistance. Among these nine SNPs, five are known to confer on rats that carry them a significant degree of resistance to anticoagulant rodenticides. These mutations are: L128Q, Y139S, L120Q, Y139C and Y139F. The latter three mutations confer, to varying degrees, practical resistance to bromadiolone and difenacoum, the two second-generation anticoagulants in predominant use in the UK. It is the recommendation of RRAG that bromadiolone and difenacoum should not be used against rats carrying the L120Q, Y139C and Y139F mutations because this will promote the spread of resistance and jeopardise the long-term efficacy of anticoagulants. Brodifacoum, flocoumafen and difethialone are effective against these three genotypes but cannot presently be used because of the regulatory restriction that they can only be applied against rats that are living and feeding predominantly indoors. Our understanding of the geographical distribution of Norway rat resistance in incomplete but is rapidly increasing. In particular, the mapping of the focus of L120Q Norway rat resistance in central-southern England by DNA sequencing is well advanced. We now know that rats carrying this resistance mutation are present across a large part of the counties of Hampshire, Berkshire and Wiltshire, and the resistance spreads into Avon, Oxfordshire and Surrey. It is also found, perhaps as outlier foci, in south-west Scotland and East Sussex. L120Q is currently the most severe form of anticoagulant resistance found in Norway rats and is prevalent over a considerable part of central-southern England. A second form of advanced Norway rat resistance is conferred by the Y139C mutation. This is noteworthy because it occurs in at least four different foci that are widely geographically dispersed, namely in Dumfries and Galloway, Gloucestershire, Yorkshire and Norfolk. Once again, bromadiolone and difenacoum are not recommended for use against rats carrying this genotype and a concern of RRAG is that continued applications of resisted active substances may result in Y139C becoming more or less ubiquitous across much of the UK. Another type of advanced resistance, the Y139F mutation, is present in Kent and Sussex. This means that Norway rats, carrying some degree of resistance to bromadiolone and difenacoum, are now found from the south coast of Kent, west into the city of Bristol, to Yorkshire in the north-east and to the south-west of Scotland. This difficult situation can only deteriorate further where these three genotypes exist and resisted anticoagulants are predominantly used against them. Resistance in house mice: House mouse is not so well understood but the presence in the UK of two resistant genotypes, L128S and Y139C, is confirmed. House mice are naturally tolerant to anticoagulants and such is the nature of this tolerance, and the presence of genetical resistance, that house mice resistant to the first-generation anticoagulants are considered to be widespread in the UK. Consequently, baits containing warfarin, sodium warfarin, chlorophacinone and coumatetralyl are not approved for use against mice. This regulatory position is endorsed by RRAG. Baits containing brodifacoum, flocoumafen and difethialone are effective against house mice and may be applied in practice because house mouse infestations are predominantly indoors. There are some reports of resistance among mice in some areas to the second-generation anticoagulant bromadiolone, while difenacoum remains largely efficacious. Alternatives to anticoagulants: The use of habitat manipulation, that is the removal of harbourage, denial of the availability of food and the prevention of ingress to structures, is an essential component of sustainable rodent pest management. All are of importance in the management of resistant rodents and have the advantage of not selecting for resistant genotypes. The use of these techniques may be particularly valuable in preventing the build-up of rat infestations. However, none can be used to remove any sizeable extant rat infestation and for practical reasons their use against house mice is problematic. Few alternative chemical interventions are available in the European Union because of the removal from the market of zinc phosphide, calciferol and bromethalin. Our virtual complete reliance on the use of anticoagulants for the chemical control of rodents in the UK, and more widely in the EU, calls for improved schemes for resistance management. Of course, these might involve the use of alternatives to anticoagulant rodenticides. Also important is an increasing knowledge of the distribution of resistance mutations in rats and mice and the use of only fully effective anticoagulants against them.

Glacial-interglacial temperature change in the tropical West Pacific: a comparison of stalagmite-based paleo-thermometers

In the tropics, geochemical records from stalagmites have so far mainly been used to qualitatively reconstruct changes in precipitation, but several new methods to reconstruct past temperatures from stalagmite material have emerged recently: i) liquid–vapor homogenization of fluid inclusion water ii) noble gas concentrations in fluid inclusion water, iii) the partitioning of oxygen isotopes between fluid inclusion water and calcite, and iv) the abundance of the 13C18O16O (‘clumped’) isotopologue in calcite. We present, for the first time, a direct comparison of these four paleo-thermometers by applying them to a fossil stalagmite covering nearly two glacial–interglacial cycles (Marine Isotope Stages (MIS) 12–9) and to two modern stalagmites, all from northern Borneo. The temperature estimates from the different methods agree in most cases within errors for both the old and recent samples; reconstructed formation temperatures of the recent samples match within 2-sigma errors with measured cave temperatures. However, slight but systematic deviations are observed between noble gas and liquid–vapor homogenization temperatures. Whereas the temperature sensitivity of fluid inclusion δ18O and clumped isotopes is currently debated, we find that the calibration of Tremaine et al. (2011) for fluid inclusion δ18O and a synthetic calcite-based clumped isotope calibration (Ziegler et al., in prep.) yield temperature estimates consistent with the other methods. All methods (with the potential exception of clumped isotopes) show excellent agreement on the amplitude of glacial–interglacial temperature change, indicating temperature shifts of 4–5 °C. This amplitude is similar to the amplitude of Mg/Ca-based regional sea surface temperature records, when correcting for sea level driven changes in cave elevation. Our reconstruction of tropical temperature evolution over the time period from 440 to 320 thousand years ago (ka) adds support to the view that climate sensitivity to varying greenhouse forcing is substantial also in the deep tropics.

Supporting local diversity of habitats and species on farmland: a comparison of three wildlife-friendly schemes

Restoration and maintenance of habitat diversity have been suggested as conservation priorities in farmed landscapes, but how this should be achieved and at what scale are unclear. This study makes a novel comparison of the effectiveness of three wildlife-friendly farming schemes for supporting local habitat diversity and species richness on 12 farms in England. The schemes were: (i) Conservation Grade (Conservation Grade: a prescriptive, non-organic, biodiversity-focused scheme), (ii) organic agriculture and (iii) a baseline of Entry Level Stewardship (Entry Level Stewardship: a flexible widespread government scheme). Conservation Grade farms supported a quarter higher habitat diversity at the 100-m radius scale compared to Entry Level Stewardship farms. Conservation Grade and organic farms both supported a fifth higher habitat diversity at the 250-m radius scale compared to Entry Level Stewardship farms. Habitat diversity at the 100-m and 250-m scales significantly predicted species richness of butterflies and plants. Habitat diversity at the 100-m scale also significantly predicted species richness of birds in winter and solitary bees. There were no significant relationships between habitat diversity and species richness for bumblebees or birds in summer. Butterfly species richness was significantly higher on organic farms (50% higher) and marginally higher on Conservation Grade farms (20% higher), compared with farms in Entry Level Stewardship. Organic farms supported significantly more plant species than Entry Level Stewardship farms (70% higher) but Conservation Grade farms did not (10% higher). There were no significant differences between the three schemes for species richness of bumblebees, solitary bees or birds. Policy implications. The wildlife-friendly farming schemes which included compulsory changes in management, Conservation Grade and organic, were more effective at increasing local habitat diversity and species richness compared with the less prescriptive Entry Level Stewardship scheme. We recommend that wildlife-friendly farming schemes should aim to enhance and maintain high local habitat diversity, through mechanisms such as option packages, where farmers are required to deliver a combination of several habitats.

Using U0126 to dissect the role of the extracellular signal-regulated kinase 1/2 (ERK1/2) cascade in the regulation of gene expression by endothelin-1 in cardiac myocytes

The hypertrophic agonist endothelin-1 rapidly but transiently activates the extracellular signal-regulated kinase 1/2 (ERK1/2) cascade (and other signalling pathways) in cardiac myocytes, but the events linking this to hypertrophy are not understood. Using Affymetrix rat U34A microarrays, we identified the short-term (2-4 h) changes in gene expression induced in neonatal myocytes by endothelin-1 alone or in combination with the ERK1/2 cascade inhibitor, U0126. Expression of 15 genes was significantly changed by U0126 alone, and expression of an additional 78 genes was significantly changed by endothelin-1. Of the genes upregulated by U0126, four are classically induced through the aryl hydrocarbon receptor (AhR) by dioxins suggesting that U0126 activates the xenobiotic response element in cardiac myocytes potentially independently of effects on ERK1/2 signalling. The 78 genes showing altered expression with endothelin-1 formed five clusters: (i) three clusters showing upregulation by endothelin-1 according to time course (4 h > 2 h; 2 h > 4 h; 2 h approximately 4 h) with at least partial inhibition by U0126; (ii) a cluster of 11 genes upregulated by endothelin-1 but unaffected by U0126 suggesting regulation through signalling pathways other than ERK1/2; (iii) a cluster of six genes downregulated by endothelin-1 with attenuation by U0126. Thus, U0126 apparently activates the AhR in cardiac myocytes (which must be taken into account in protracted studies), but careful analysis allows identification of genes potentially regulated acutely via the ERK1/2 cascade. Our data suggest that the majority of changes in gene expression induced by endothelin-1 are mediated by the ERK1/2 cascade.

Two new species of Pamphobeteus Pocock 1901 (Araneae : Mygalomorphae : Theraphosidae) from Brazil, with a new type of stridulatory organ

Two new species of Pamphobeteus Pocock 1901 are described from Brazil: Pamphobeteus crassifemur sp. nov. and Pamphobeteus grandis sp. nov.; Pamphobeteus nigricolor, formerly described from Colombia, Ecuador and Bolivia, is recorded from Brazil and its distribution in Ecuador and Bolivia is questioned. A new type of stridulatory organ is described from legs III and IV of P. crassifemur sp. nov. The structure consists of spiniform setae. Stridulation occurs when the spider moves the legs III and IV, sometimes while shedding urticating hairs.

Thymine hydroperoxide as a potential source of singlet molecular oxygen in DNA

The decomposition of organic hydroperoxides into peroxyl radicals is a potential source of singlet molecular oxygen [O(2) ((1)Delta(g))] in biological systems. This study shows that 5-(hydroperoxymethyl)uracil (5-HPMU), a thymine hydroperoxide within DNA, reacts with metal ions or HOCl, generating O(2) ((1)Delta(g)). Spectroscopic evidence for generation of O(2) ((1)Delta(g)) was obtained by measuring (i) the bimolecular decay, (ii) the monomolecular decay, and (iii) the observation of D(2)O enhancement of O(2) ((1)Delta(g)) production and the quenching effect of NaN(3). Moreover, the presence of O(2) ((1)Delta(g)) was unequivocally demonstrated by the direct characterization of the near-infrared light emission. For the sake of comparison, O(2) ((1)Delta(g)) derived from the H(2)O(2)/HOCl system and from the thermolysis of the N,N`-di(2,3-dihydroxypropyl)-1,4-naphthalenedipropanamide endoperoxide was also monitored. More evidence of O(2) ((1)Delta(g)) generation was obtained by chemical trapping of O(2) ((1)Delta(g)) with anthracene-9,10-divinylsulfonate (AVS) and detection of the specific AVS endoperoxide by HPLC/MS/MS. The detection by HPLC/MS of 5-(hydroxymethyl)uracil and 5-formyluracil, two thymine oxidation products generated from the reaction of 5-HPMU and Ce(4+) ions, supports the Russell mechanism. These photoemission properties and chemical trapping clearly demonstrate that the decomposition of 5-HPMU generates O(2) ((1)Delta(g)) by the Russell mechanism and point to the involvement of O(2) ((1)Delta(g)) in thymidine hydroperoxide cytotoxicity. (C) 2009 Elsevier Inc. All rights reserved.

A Ring Contraction Strategy toward a Diastereoselective Total Synthesis of (+)-Bakkenolide A

A diastereoselective route to (+)-bakkenolide A is presented from the readily available optically active Wieland-Miescher ketone. This novel synthesis of this sesquiterpene lactone features the following as key stereoselective transformations: (i) the ring contraction reaction of a octalone mediated by thallium(III) nitrate (TTN); (ii) a hydrogenation to create the cis-fused junction; and (iii) the formation of the C7 quaternary center through an enolate intermediate. Furthermore, during this work, the absolute configuration of a trinorsesquiterpene isolated from Senecio Humillimus was assigned.

Nordic Journal of English Studies : Irish Studies in the Nordic Countries

This special issue of Nordic Journal of English Studies is devoted to the research in Irish Studies being carried out in Scandinavia by a group of scholars based in Denmark, Norway and Sweden, as well as scholars associated—in one way or another—with Scandinavia. Denmark is represented by the University of Aalborg; Norway, by scholars affiliated to the Universities of Agder, the Artic University of Norway, Bergen, and Stavanger; and Sweden is represented by scholars from the universities of Dalarna, Göteborg, Stockholm, Södertörn and Umeå. Included also in this special issue is the work of two former students, who completed their Masters’ degree in Irish literature at DUCIS (Dalarna University Centre for Irish Studies), Sweden—from Norway and China respectively. The collection also contains an article by Dara Waldron, Limerick Institute of Technology, Ireland, whof recently presented his research at the Higher Seminar in Dalarna. Contributions by the Irish poet, Mary O’Donnell, who participated in the Nordic Irish Studies Network (NISN) conference, hosted by DUCIS in December 2012, are also included.

Pedal : identification of models for duodenal administration of levodopa

Backgound and aims: The main purpose of the PEDAL study is to identify and estimate sample individual pharmacokinetic- pharmacodynamic (PK/PD) models for duodenal infusion of levodopa/carbidopa (Duodopa®) that can be used for in numero simulation of treatment strategies. Other objectives are to study the absorption of Duodopa® and to form a basis for power calculation for a future larger study. PK/PD based on oral levodopa is problematic because of irregular gastric emptying. Preliminary work with data from [Gundert-Remy U et al. Eur J Clin Pharmacol 1983;25:69-72] suggested that levodopa infusion pharmacokinetics can be described by a two-compartment model. Background research led to a hypothesis for an effect model incorporating concentration-unrelated fluctuations, more complex than standard E-max models. Methods: PEDAL involved a few patients already on Duodopa®. A bolus dose (normal morning dose plus 50%) was given after a washout during night. Data collection continued until the clinical effect was back at baseline. The procedure was repeated on two non-consecutive days per patient. The following data were collected in 5 to 15 minutes intervals: i) Accelerometer data. ii) Three e-diary questions about ability to walk, feelings of “off” and “dyskinesia”. iii) Clinical assessment of motor function by a physician. iv) Plasma concentrations of levodopa, carbidopa and the metabolite 3-O-methyldopa. The main effect variable will be the clinical assessment. Results: At date of abstract submission, lab analyses were currently being performed. Modelling results, simulation experiments and conclusions will be presented in our poster.

First-principle data-driven models for assessment of motor disorders in Parkinson’s disease

Parkinson’s disease (PD) is an increasing neurological disorder in an aging society. The motor and non-motor symptoms of PD advance with the disease progression and occur in varying frequency and duration. In order to affirm the full extent of a patient’s condition, repeated assessments are necessary to adjust medical prescription. In clinical studies, symptoms are assessed using the unified Parkinson’s disease rating scale (UPDRS). On one hand, the subjective rating using UPDRS relies on clinical expertise. On the other hand, it requires the physical presence of patients in clinics which implies high logistical costs. Another limitation of clinical assessment is that the observation in hospital may not accurately represent a patient’s situation at home. For such reasons, the practical frequency of tracking PD symptoms may under-represent the true time scale of PD fluctuations and may result in an overall inaccurate assessment. Current technologies for at-home PD treatment are based on data-driven approaches for which the interpretation and reproduction of results are problematic.  The overall objective of this thesis is to develop and evaluate unobtrusive computer methods for enabling remote monitoring of patients with PD. It investigates first-principle data-driven model based novel signal and image processing techniques for extraction of clinically useful information from audio recordings of speech (in texts read aloud) and video recordings of gait and finger-tapping motor examinations. The aim is to map between PD symptoms severities estimated using novel computer methods and the clinical ratings based on UPDRS part-III (motor examination). A web-based test battery system consisting of self-assessment of symptoms and motor function tests was previously constructed for a touch screen mobile device. A comprehensive speech framework has been developed for this device to analyze text-dependent running speech by: (1) extracting novel signal features that are able to represent PD deficits in each individual component of the speech system, (2) mapping between clinical ratings and feature estimates of speech symptom severity, and (3) classifying between UPDRS part-III severity levels using speech features and statistical machine learning tools. A novel speech processing method called cepstral separation difference showed stronger ability to classify between speech symptom severities as compared to existing features of PD speech. In the case of finger tapping, the recorded videos of rapid finger tapping examination were processed using a novel computer-vision (CV) algorithm that extracts symptom information from video-based tapping signals using motion analysis of the index-finger which incorporates a face detection module for signal calibration. This algorithm was able to discriminate between UPDRS part III severity levels of finger tapping with high classification rates. Further analysis was performed on novel CV based gait features constructed using a standard human model to discriminate between a healthy gait and a Parkinsonian gait. The findings of this study suggest that the symptom severity levels in PD can be discriminated with high accuracies by involving a combination of first-principle (features) and data-driven (classification) approaches. The processing of audio and video recordings on one hand allows remote monitoring of speech, gait and finger-tapping examinations by the clinical staff. On the other hand, the first-principles approach eases the understanding of symptom estimates for clinicians. We have demonstrated that the selected features of speech, gait and finger tapping were able to discriminate between symptom severity levels, as well as, between healthy controls and PD patients with high classification rates. The findings support suitability of these methods to be used as decision support tools in the context of PD assessment.

Analysis of the economic and financial relations between Latin American and the Caribbean and the BRICS group

This document has been prepared in compliance with Activity III.1.2 of the Work Programme of SELA for the year 2015, entitled “Analysis of the economic and financial relations between Latin America and the Caribbean and the BRICS countries”. The document comprises an introduction, four chapters and a final section with the conclusions and recommendations stemming from the study. Chapter I describes the economic performance of the BRICS countries, their economic relations with Latin America and the Caribbean and the functioning of the development banks of the member countries. Chapter II assesses the financial architecture of Latin America and the Caribbean and explores the needs for financing in the region. Chapter III deals with the regulatory frameworks governing public and private investments in Latin America and the Caribbean and the Bilateral Investment Treaties with the BRICS countries. Finally, Chapter IV describes the main features of the New Development Bank (NDB) and the Contingent Reserve Agreement of the BRICS

Identification and antimicrobial susceptibility patterns of Pasteurella multocida isolated from chickens and japanese quails in Brazil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efficacy of several Salmonella vaccination programs against experimental challenge with Salmonella gallinarum in commercial brown layer and broiler breeder hens

The protective effect of various Salmonella vaccines regimens against an experimental Salmonella Gallinarum challenge (SGNalr strain at 12 wk of age) was evaluated in two experiments. In Experiment 1 commercial brown layers were vaccinated according to one of the following programs: (i) two doses of a SE bacterin (Layermune SE; group 1); (ii) a first dose of a live SG9R vaccine (Cevac SG9R) followed by a SE bacterin (Layermune SE; group 2); (iii) one dose of each of two different multivalent inactivated vaccines containing SE cells (Corymune 4 & Corymune 7; group 3) or (iv) not vaccinated (group 4). In Experiment 2, broiler breeders were given the same vaccination treatments except for the group vaccinated with the multivalent vaccines. Overall, in both experiments, all vaccination schemes were effective in reducing mortality after challenge with a SG field strain. Primary vaccination with an initial dose of a live SG9R vaccine followed some weeks later by a dose of an inactivated SE bacterin was the most effective (p<0.05) vaccination program against mortality induced by field SG experimental challenge in both experiments. In conclusion, Salmonella vaccination programs containing SE bacterins alone or in combination with a live SG9R vaccine are effective in preventing mortality induced by infection of field SG. Nevertheless, it is important to emphasize that any vaccination program against any Salmonella serotype will only be effective if it is part of a sound and comprehensive biosecurity program designed for Salmonella control in poultry farms.

Effect of polyunsaturated fatty acids on the fecundity of the Amazon river prawn Macrobrachium amazonicum (Heller, 1862)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)