The EC REACH Regulation and contractual supply obligations

REACH, as an EC legislative instrument in the form of a community regulation, is directly applicable in the national domestic laws of each of the 30 states in the European Economic Area (EEA). REACH now takes effect within the context of the Treaty on the Functioning of the European Union (TFEU) and the Treaty on European Union (TEU), both of which entered into force under the Treaty of Lisbon on December 1, 2009 and replace, as from that date, the prior governing Treaties of the European Union (EU). REACH prohibits the placing of registrable substances, on their own, or in preparations or articles, on the market in the EEA unless they have been registered and, when required, their use authorised in accordance with REACH. It also places obligations on sellers and buyers of such substances (or of preparations--and in certain circumstances even articles containing them) to pass product, risk and use information both up and down the supply chain and also to the European Chemicals Agency (ECHA), which is effectively responsible for managing the registration, authorisation and restriction process across the EEA and for co-ordinating the implementation of REACH by the EEA states. REACH has the capacity to have direct effects on the rights and duties of parties buying and selling within, and into, the EEA

Should insurance risk avoidance be reformed and would reform be of a right of equitable rescission or a right sui generis?

This article explores the distinction between the alternative explanations for the remedy of insurance risk avoidance in the event of breach of the duty of utmost good faith. It asks whether the remedy is an avoidance of a void contract, or a rescission of a voidable contract. The article then considers the general significance of that distinction to the capacity of a party to exercise its primary right of avoidance, and to the secondary rights of the contracting parties - arising in consequence of the avoidance - to prevent unjust enrichment or achieve restitution. Before considering the potential for - and the desirability of - further reform in the area, the article evaluates the importance of the legal characterisation of insurance risk avoidance in the particular context of insurance contracts affording indemnity to multiple insured parties

Dihydropyrimidine dehydrogenase deficiency and fluorouracil-related toxicity

Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme of 5-fluorouracil (5-FU) catabolism. We report lymphocytic DPD data concerning a group of 53 patients (23 men, 30 women, mean age 58, range 36–73), treated by 5-FU-based chemotherapy in different French institutions and who developed unanticipated 5-FU-related toxicity. Lymphocyte samples (standard collection procedure) were sent to us for DPD determination (biochemical method). Among the whole group of 53 patients, 19 had a significant DPD deficiency (DD; below 150 fmol min−1 mg−1 protein, i.e. less than 70% of the mean value observed from previous population study). There was a greater majority of women in the DD group (15 out of 19, 79%) compared with the remaining 34 patients (15 out of 34, 44%, P<0.014). Toxicity was often severe, leading to patient death in two cases (both women). The toxicity score (sum of WHO grading, theoritical range 0–20) was twice as high in patients with marked DD (below 100 pmol min−1 mg−1 protein, n = 11, mean score = 13.2) compared with patients with moderate DD (between 150 and 100 pmol min−1 mg−1 protein, n = 8, mean score = 6.8), P = 0.008. In the DD group, there was a high frequency of neurotoxic syndromes (7 out of 19, 37%). The two deceased patients both had severe neurotoxicity. The occurrence of cardiac toxicity was relatively rare (1 out of 19, 5%). These data suggest that women are particularly prone to DPD deficiency and allow a more precise definition of the DD toxicity profile. © 1999 Cancer Research Campaig

Multisensory information facilitates reaction speed by enlarging activity difference between superior colliculus hemispheres in rats

Animals can make faster behavioral responses to multisensory stimuli than to unisensory stimuli. The superior colliculus (SC), which receives multiple inputs from different sensory modalities, is considered to be involved in the initiation of motor responses. However, the mechanism by which multisensory information facilitates motor responses is not yet understood. Here, we demonstrate that multisensory information modulates competition among SC neurons to elicit faster responses. We conducted multiunit recordings from the SC of rats performing a two-alternative spatial discrimination task using auditory and/or visual stimuli. We found that a large population of SC neurons showed direction-selective activity before the onset of movement in response to the stimuli irrespective of stimulation modality. Trial-by-trial correlation analysis showed that the premovement activity of many SC neurons increased with faster reaction speed for the contraversive movement, whereas the premovement activity of another population of neurons decreased with faster reaction speed for the ipsiversive movement. When visual and auditory stimuli were presented simultaneously, the premovement activity of a population of neurons for the contraversive movement was enhanced, whereas the premovement activity of another population of neurons for the ipsiversive movement was depressed. Unilateral inactivation of SC using muscimol prolonged reaction times of contraversive movements, but it shortened those of ipsiversive movements. These findings suggest that the difference in activity between the SC hemispheres regulates the reaction speed of motor responses, and multisensory information enlarges the activity difference resulting in faster responses

Video-tracking and On-plant Tests Show Cry1Ab Resistance Influences Behavior and Survival of Neonate Ostrinia nubilalis Following Exposure to Bt Maize

To examine how resistance to Bacillus thuringiensis (Bt) toxins influences movement and survival of European corn borer (Ostrinia nubilalis [Hübner]) neonates, the responses of Cry1Ab-resistant , -susceptible, and hybrid (F1) larvae were examined using two different techniques. First, using an automated video-tracking system, aspects of O. nubilalis movement were quantified in the presence of artificial diet incorporating 50% non-Bt or insect-resistant Cry1Ab maize tissue. Second, O. nubilalis dispersal and survival were measured 48–72 h after hatching on a Cry1Ab maize plant surrounded by two non-Bt maize plants. Video tracking indicated the presence of Cry1Ab tissue increased the total distance moved (m), time moving (%), and time away from the diet (%) for O. nubilalis while decreasing meander (degrees/cm). However, resistant larvae showed reduced movement and increased meander (≈localized searching) relative to susceptible or hybrid larvae on diet incorporating Cry1Ab tissue. Conversely, when placed onto Cry1Ab maize plants, resistant larvae were more likely than susceptible O. nubilalis to disperse onto adjacent non-Bt plants. The difference in on-plant dispersal seems to reflect greater survival after toxin exposure for resistant larvae rather than increased activity. These results suggest that simplified ‘Petri dish’ tests may not be predictive of larval movement among non-Bt and insect-resistant Bt maize plants. Because models of O. nubilalis resistance evolution incorporate various movement and survival parameters, improved data for on-plant behavior and survival of Bt- resistant , -susceptible, and hybrid larvae should help preserve the efficacy of transgenic insect-resistant maize

Critical behaviour of a surface reaction model with infinitely many absorbing states

In a recent letter [J. Phys. A26, L801 (1993)], Yaldram et al. studied the critical behaviour of a simple lattice gas model of the CO-NO catalytic reaction. The model exhibits a second order nonequilibrium phase transition from an active state into one out of infinitely many absorbing states. Estimates for the critical exponent $\beta$ suggested that the model belongs to a new universality class. The results reported in this article contradict this notion, as estimates for various critical exponents show that the model belongs to the universality class of directed percolation.Comment: 10p+5fig, LaTeX+fig in uuencoded P

Cryotomography of budding influenza a virus reveals filaments with diverse morphologies that mostly do not bear a genome at their distal end

Influenza viruses exhibit striking variations in particle morphology between strains. Clinical isolates of influenza A virus have been shown to produce long filamentous particles while laboratory-adapted strains are predominantly spherical. However, the role of the filamentous phenotype in the influenza virus infectious cycle remains undetermined. We used cryo-electron tomography to conduct the first three-dimensional study of filamentous virus ultrastructure in particles budding from infected cells. Filaments were often longer than 10 microns and sometimes had bulbous heads at their leading ends, some of which contained tubules we attribute to M1 while none had recognisable ribonucleoprotein (RNP) and hence genome segments. Long filaments that did not have bulbs were infrequently seen to bear an ordered complement of RNPs at their distal ends. Imaging of purified virus also revealed diverse filament morphologies; short rods (bacilliform virions) and longer filaments. Bacilliform virions contained an ordered complement of RNPs while longer filamentous particles were narrower and mostly appeared to lack this feature, but often contained fibrillar material along their entire length. The important ultrastructural differences between these diverse classes of particles raise the possibility of distinct morphogenetic pathways and functions during the infectious process

Classification of fibroglandular tissue distribution in the breast based on radiotherapy planning CT

Accurate segmentation of breast tissues is required for a number of applications such as model based deformable registration in breast radiotherapy. The accuracy of breast tissue segmentation is affected by the spatial distribution (or pattern) of fibroglandular tissue (FT). The goal of this study was to develop and evaluate texture features, determined from planning computed tomography (CT) data, to classify the spatial distribution of FT in the breas

Reliability of the interRAI suite of assessment instruments: a 12-country study of an integrated health information system

<p>Abstract</p> <p>Background</p> <p>A multi-domain suite of instruments has been developed by the interRAI research collaborative to support assessment and care planning in mental health, aged care and disability services. Each assessment instrument comprises items common to other instruments and specialized items exclusive to that instrument. This study examined the reliability of the items from five instruments supporting home care, long term care, mental health, palliative care and post-acute care.</p> <p>Methods</p> <p>Paired assessments on 783 individuals across 12 nations were completed within 72 hours of each other by trained assessors who were blinded to the others' assessment. Reliability was tested using weighted kappa coefficients.</p> <p>Results</p> <p>The overall kappa mean value for 161 items which are common to 2 or more instruments was 0.75. The kappa mean value for specialized items varied among instruments from 0.63 to 0.73. Over 60% of items scored greater than 0.70.</p> <p>Conclusion</p> <p>The vast majority of items exceeded standard cut-offs for acceptable reliability, with only modest variation among instruments. The overall performance of these instruments showed that the interRAI suite has substantial reliability according to conventional cut-offs for interpreting the kappa statistic. The results indicate that interRAI items retain reliability when used across care settings, paving the way for cross domain application of the instruments as part of an integrated health information system.</p

Hospitalized Children with 2009 Pandemic Influenza A (H1N1): Comparison to Seasonal Influenza and Risk Factors for Admission to the ICU

BACKGROUND: Limited data are available describing the clinical presentation and risk factors for admission to the intensive care unit for children with 2009 H1N1 infection. METHODS: We conducted a retrospective chart review of all hospitalized children with 2009 influenza A (H1N1) and 2008-09 seasonal influenza at The Children's Hospital, Denver, Colorado. RESULTS: Of the 307 children identified with 2009 H1N1 infections, the median age was 6 years, 61% were male, and 66% had underlying medical conditions. Eighty children (26%) were admitted to the ICU. Thirty-two (40%) of the ICU patients required intubation and 17 (53%) of the intubated patients developed acute respiratory distress syndrome (ARDS). Four patients required extracorporeal membrane oxygenation. Eight (3%) of the hospitalized children died. Admission to the ICU was significantly associated with older age and underlying neurological condition. Compared to the 90 children admitted during the 2008-09 season, children admitted with 2009 H1N1 influenza were significantly older, had a shorter length of hospitalization, more use of antivirals, and a higher incidence of ARDS. CONCLUSIONS: Compared to the 2008-09 season, hospitalized children with 2009 H1N1 influenza were much older and had more severe respiratory disease. Among children hospitalized with 2009 H1N1 influenza, risk factors for admission to the ICU included older age and having an underlying neurological condition. Children under the age of 2 hospitalized with 2009 H1N1 influenza were significantly less likely to require ICU care compared to older hospitalized children