Whisker spot patterns: a noninvasive method of individual identification of Australian sea lions (Neophoca cinerea)

Reliable methods for identification of individual animals are advantageous for ecological studies of population demographics and movement patterns. Photographic identification, based on distinguishable patterns, unique shapes, or scars, is an effective technique already used for many species. We tested whether photographs of whisker spot patterns could be used to discriminate among individual Australian sea lion (Neophoca cinerea). Based on images of 53 sea lions, we simulated 5,000 patterns before calculating the probability of duplication in a study population. A total of 99% (± 1.5 SD) of patterns were considered reliable for a population of 50, 98% (± 1.7 SD) for 100, 92% (± 4.7 SD) for 500, and 88% (± 5.7 SD) for 1,000. We tested a semiautomatic approach by matching 16 known individuals at 3 different angles (70°, 90°, and 110°), 2 distances (1 and 2 m), and 6 separate times over a 1-year period. A point-pattern matching algorithm for pairwise comparisons produced 90% correct matches of photographs taken on the same day at 90°. Images of individuals at 1 and 2 m resulted in 89% correct matches, those photographed at different angles and different times (at 90°) resulted in 48% and 73% correct matches, respectively. Our results show that the Chamfer distance transform can effectively be used for individual identification, but only if there is very little variation in photograph angle. This point-pattern recognition application may also work for other otariid species

Elevated expression of the chemokine-scavenging receptor D6 is associated with impaired lesion development in psoriasis

D6 is a scavenging-receptor for inflammatory CC chemokines that are essential for resolution of inflammatory responses in mice. Here, we demonstrate that D6 plays a central role in controlling cutaneous inflammation, and that D6 deficiency is associated with development of a psoriasis-like pathology in response to varied inflammatory stimuli in mice. Examination of D6 expression in human psoriatic skin revealed markedly elevated expression in both the epidermis and lymphatic endothelium in "uninvolved" psoriatic skin (ie, skin that was more than 8 cm distant from psoriatic plaques). Notably, this increased D6 expression is associated with elevated inflammatory chemokine expression, but an absence of plaque development, in uninvolved skin. Along with our previous observations of the ability of epidermally expressed transgenic D6 to impair cutaneous inflammatory responses, our data support a role for elevated D6 levels in suppressing inflammatory chemokine action and lesion development in uninvolved psoriatic skin. D6 expression consistently dropped in perilesional and lesional skin, coincident with development of psoriatic plaques. D6 expression in uninvolved skin also was reduced after trauma, indicative of a role for trauma-mediated reduction in D6 expression in triggering lesion development. Importantly, D6 is also elevated in peripheral blood leukocytes in psoriatic patients, indicating that upregulation may be a general protective response to inflammation. Together our data demonstrate a novel role for D6 as a regulator of the transition from uninvolved to lesional skin in psoriasis

Neurologists’ experiences of participating in the CODES study—A multicentre randomised controlled trial comparing cognitive behavioural therapy vs standardised medical care for dissociative seizures

Purpose We investigated neurologists’ experience of participating in the large CODES trial involving around 900 adults with dissociative seizures which subsequently evaluated the effectiveness of tailored cognitive behavioural therapy (CBT) plus standardised medical care versus standardised medical care alone in 368 patients with dissociative seizures. Method We asked all neurologists referring patients with dissociative seizures to the CODES study to complete a 43-item online survey. This examined neurologists’ (i) demographics, (ii) knowledge of dissociative seizures before and after their involvement in the CODES trial, (iii) clinical practice before, during and since their involvement, and (iv) their experience of the CODES trial. Results Forty-three (51%) neurologists completed the questionnaire. Only about half of neurologists could make referrals to psychological intervention specific for dissociative seizures before and after the trial. One-third of doctors reported having changed their referral practice following their involvement. The majority (>69%) agreed that patient satisfaction with different aspects of the trial was very high, and 83.7% thought that it was easy to recruit patients for the study. Over 90% agreed they would like the treatment pathway to continue. Respondents found different elements of the trial useful, in particular, the patient factsheet booklet (98%), diagnosis communication advice (93%) and the CBT package (93%). Conclusions Neurologists participating in CODES generally found it easy to recruit patients and perceived patient satisfaction as very high. However, 46.5% of neurologists could not offer psychotherapy once the trial had finished, suggesting that problems with lack of access to psychological treatment for dissociative seizures persist

MICL controls inflammation in rheumatoid arthritis

Acknowledgments We thank G Milne, D MacCallum, S Hardison, G Wilson, C Wallace, S Hadebe and A Richmond for assistance; H. El-Gabalawy for tissues and the animal facility staff for the care of our animals. Flow cytometry was undertaken in the Iain Fraser Cytometry Centre, University of Aberdeen. Funding: GDB was funded by the Wellcome Trust and MRC (UK). AA and CDB are supported by the Arthritis Research UK Tissue Engineering Centre (grant 19429). This study makes use of data generated by the Wellcome Trust Case Control Consortium. A full list of the investigators who contributed to the generation of the data is available from http://www.wtccc.org.uk, and was funded by the Wellcome Trust (076113). MJGF was funded by The Arthritis Society and the Canadian Arthritis Network and J-ML by a scholarship from the Canadian Arthritis Network.Peer reviewedPublisher PD

Pacific Ocean–wide profile of CYP1A1 expression, stable carbon and nitrogen isotope ratios, and organic contaminant burden in sperm whale skin biopsies

This paper is not subject to U.S. copyright. The definitive version was published in Environmental Health Perspectives 119 (2011): 337-343, doi:10.1289/ehp.0901809.Background: Ocean pollution affects marine organisms and ecosystems as well as humans. The International Oceanographic Commission recommends ocean health monitoring programs to investigate the presence of marine contaminants and the health of threatened species and the use of multiple and early-warning biomarker approaches. Objective: We explored the hypothesis that biomarker and contaminant analyses in skin biopsies of the threatened sperm whale (Physeter macrocephalus) could reveal geographical trends in exposure on an oceanwide scale. Methods: We analyzed cytochrome P450 1A1 (CYP1A1) expression (by immunohistochemistry), stable nitrogen and carbon isotope ratios (as general indicators of trophic position and latitude, respectively), and contaminant burdens in skin biopsies to explore regional trends in the Pacific Ocean. Results: Biomarker analyses revealed significant regional differences within the Pacific Ocean. CYP1A1 expression was highest in whales from the Galapagos, a United Nations Educational, Scientific, and Cultural Organization World Heritage marine reserve, and was lowest in the sampling sites farthest away from continents. We examined the possible influence of the whales’ sex, diet, or range and other parameters on regional variation in CYP1A1 expression, but data were inconclusive. In general, CYP1A1 expression was not significantly correlated with contaminant burdens in blubber. However, small sample sizes precluded detailed chemical analyses, and power to detect significant associations was limited. Conclusions: Our large-scale monitoring study was successful at identifying regional differences in CYP1A1 expression, providing a baseline for this known biomarker of exposure to aryl hydrocarbon receptor agonists. However, we could not identify factors that explained this variation. Future oceanwide CYP1A1 expression profiles in cetacean skin biopsies are warranted and could reveal whether globally distributed chemicals occur at biochemically relevant concentrations on a global basis, which may provide a measure of ocean integrity.Funding was provided by National Institute of Environmental Health Sciences grant P42-ES-0469, Superfund Basic Research Program grant P42ES007381, NOAA Sea Grant NA86RG0075 R/B-162, and the Ocean Alliance

Recognition and control of neutrophil extracellular trap formation by MICL

Acknowledgements We thank the staff of the animal facilities at the University of Aberdeen and the University of Exeter for support and care for animals; C. Paterson from the University of Glasgow for assistance in establishing a Material Transfer Agreement; C. Parkin and D. Thompson for support with microscopy; and M. Stacey for valuable input. We acknowledge funding from the Wellcome Trust (102705 and 097377), Versus Arthritis (21164, 20775 and 21156), the US National Institutes of Health (R01DK121977 and R01AI163007), Versus Arthritis Centre of Excellence, Medical Research Council (MR/L020211/1) and the MRC Centre for Medical Mycology (MR/N006364/1). SLE tissue samples were provided by the Imperial College Healthcare Tissue Bank funded by the National Institute for Health Research (NIHR), Biomedical Research Centre based at the Imperial College Healthcare NHS Trust and Imperial College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.Peer reviewe

Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis (New EPOC): long-term results of a multicentre, randomised, controlled, phase 3 trial.

BACKGROUND: The interim analysis of the multicentre New EPOC trial in patients with resectable colorectal liver metastasis showed a significant reduction in progression-free survival in patients allocated to cetuximab plus chemotherapy compared with those given chemotherapy alone. The focus of the present analysis was to assess the effect on overall survival. METHODS: New EPOC was a multicentre, open-label, randomised, controlled, phase 3 trial. Adult patients (aged ≥18 years) with KRAS wild-type (codons 12, 13, and 61) resectable or suboptimally resectable colorectal liver metastases and a WHO performance status of 0-2 were randomly assigned (1:1) to receive chemotherapy with or without cetuximab before and after liver resection. Randomisation was done centrally with minimisation factors of surgical centre, poor prognosis cancer, and previous adjuvant treatment with oxaliplatin. Chemotherapy consisted of oxaliplatin 85 mg/m2 administered intravenously over 2 h, l-folinic acid (175 mg flat dose administered intravenously over 2 h) or d,l-folinic acid (350 mg flat dose administered intravenously over 2 h), and fluorouracil bolus 400 mg/m2 administered intravenously over 5 min, followed by a 46 h infusion of fluorouracil 2400 mg/m2 repeated every 2 weeks (regimen one), or oxaliplatin 130 mg/m2 administered intravenously over 2 h and oral capecitabine 1000 mg/m2 twice daily on days 1-14 repeated every 3 weeks (regimen two). Patients who had received adjuvant oxaliplatin could receive irinotecan 180 mg/m2 intravenously over 30 min with fluorouracil instead of oxaliplatin (regimen three). Cetuximab was given intravenously, 500 mg/m2 every 2 weeks with regimen one and three or a loading dose of 400 mg/m2 followed by a weekly infusion of 250 mg/m2 with regimen two. The primary endpoint of progression-free survival was published previously. Secondary endpoints were overall survival, preoperative response, pathological resection status, and safety. Trial recruitment was halted prematurely on the advice of the Trial Steering Committee on Nov 1, 2012. All analyses (except safety) were done on the intention-to-treat population. Safety analyses included all randomly assigned patients. This trial is registered with ISRCTN, number 22944367. FINDINGS: Between Feb 26, 2007, and Oct 12, 2012, 257 eligible patients were randomly assigned to chemotherapy with cetuximab (n=129) or without cetuximab (n=128). This analysis was carried out 5 years after the last patient was recruited, as defined in the protocol, at a median follow-up of 66·7 months (IQR 58·0-77·5). Median progression-free survival was 22·2 months (95% CI 18·3-26·8) in the chemotherapy alone group and 15·5 months (13·8-19·0) in the chemotherapy plus cetuximab group (hazard ratio [HR] 1·17, 95% CI 0·87-1·56; p=0·304). Median overall survival was 81·0 months (59·6 to not reached) in the chemotherapy alone group and 55·4 months (43·5-71·5) in the chemotherapy plus cetuximab group (HR 1·45, 1·02-2·05; p=0·036). There was no significant difference in the secondary outcomes of preoperative response or pathological resection status between groups. Five deaths might have been treatment-related (one in the chemotherapy alone group and four in the chemotherapy plus cetuximab group). The most common grade 3-4 adverse events reported were: neutrophil count decreased (26 [19%] of 134 in the chemotherapy alone group vs 21 [15%] of 137 in the chemotherapy plus cetuximab group), diarrhoea (13 [10%] vs 14 [10%]), skin rash (one [1%] vs 22 [16%]), thromboembolic events (ten [7%] vs 11 [8%]), lethargy (ten [7%] vs nine [7%]), oral mucositis (three [2%] vs 14 [10%]), vomiting (seven [5%] vs seven [5%]), peripheral neuropathy (eight [6%] vs five [4%]), and pain (six [4%] vs six [4%]). INTERPRETATION: Although the addition of cetuximab to chemotherapy improves the overall survival in some studies in patients with advanced, inoperable metastatic disease, its use in the perioperative setting in patients with operable disease confers a significant disadvantage in terms of overall survival. Cetuximab should not be used in this setting. FUNDING: Cancer Research UK

How can we achieve a sustainable nuclear fuel cycle?

Dealing with spent nuclear fuel is key if nuclear fission is to be used more widely going forward. Nuclear power is close to carbon neutral, but spent nuclear fuel has a storage lifetime of ~300,000 years. Reprocessing spent nuclear fuel is carried out on large scale using the PUREX “Plutonium Uranium Reduction and Extraction” process. The spent nuclear fuel is reduced to 15% of its original weight and the separated uranium and plutonium reused as “Mixed Oxide Fuel”. In the civil sector, this was carried out by the UK at Sellafield (now curtailed) and continues in France at La Hague. A plant in Rokashamura in Japan has been mothballed after the Fukushima accident. The residual waste must be stored for ~9,000 years with most of the remaining radiotoxicity due to traces of the minor actinides, neptunium, americium and curium, constituting just 0.1% of the original spent fuel. Separation of these minor actinides from the chemically very similar lanthanides (rare earths) in the last 15% of waste remaining after PUREX is the key step for future reprocessing. If separated, the minor actinides can be used as fuel in the next generation of nuclear reactors and converted into benign products, but lanthanides will cause the fission process to shut down if introduced into the reactor pile as they absorb neutrons efficiently. Removing the minor actinides from post PUREX waste will mean that the final residue need only be stored for 300 years. The highly challenging separation of the chemically very similar minor actinides from the lanthanides has been achieved using nitrogen-bearing organic ligands developed at Reading University. This can lead to significantly improved handling of spent nuclear fuels and means that waste nuclear fuel need not be a long-term storage liability but a source of yet more clean power

Community-Wide Assessment of Protein-Interface Modeling Suggests Improvements to Design Methodology

The CAPRI and CASP prediction experiments have demonstrated the power of community wide tests of methodology in assessing the current state of the art and spurring progress in the very challenging areas of protein docking and structure prediction. We sought to bring the power of community wide experiments to bear on a very challenging protein design problem that provides a complementary but equally fundamental test of current understanding of protein-binding thermodynamics. We have generated a number of designed protein-protein interfaces with very favorable computed binding energies but which do not appear to be formed in experiments, suggesting there may be important physical chemistry missing in the energy calculations. 28 research groups took up the challenge of determining what is missing: we provided structures of 87 designed complexes and 120 naturally occurring complexes and asked participants to identify energetic contributions and/or structural features that distinguish between the two sets. The community found that electrostatics and solvation terms partially distinguish the designs from the natural complexes, largely due to the non-polar character of the designed interactions. Beyond this polarity difference, the community found that the designed binding surfaces were on average structurally less embedded in the designed monomers, suggesting that backbone conformational rigidity at the designed surface is important for realization of the designed function. These results can be used to improve computational design strategies, but there is still much to be learned; for example, one designed complex, which does form in experiments, was classified by all metrics as a non-binder

Les droits disciplinaires des fonctions publiques : « unification », « harmonisation » ou « distanciation ». A propos de la loi du 26 avril 2016 relative à la déontologie et aux droits et obligations des fonctionnaires

The production of tt‾ , W+bb‾ and W+cc‾ is studied in the forward region of proton–proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98±0.02 fb−1 . The W bosons are reconstructed in the decays W→ℓν , where ℓ denotes muon or electron, while the b and c quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions.The production of $t\overline{t}$, $W+b\overline{b}$ and $W+c\overline{c}$ is studied in the forward region of proton-proton collisions collected at a centre-of-mass energy of 8 TeV by the LHCb experiment, corresponding to an integrated luminosity of 1.98 $\pm$ 0.02 \mbox{fb}^{-1}. The $W$ bosons are reconstructed in the decays $W\rightarrow\ell\nu$, where $\ell$ denotes muon or electron, while the $b$ and $c$ quarks are reconstructed as jets. All measured cross-sections are in agreement with next-to-leading-order Standard Model predictions