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As treatment of the early, inflammatory phase of sepsis improves, post-sepsis immunosuppression and secondary infection have increased in importance. How early inflammation drives immunosuppression remains unclear. Although IFN-γ typically helps microbial clearance, we found that increased plasma IFN-γ in early clinical sepsis was associated with the later development of secondary Candida infection. Consistent with this observation, we found that exogenous IFN-γ suppressed macrophage phagocytosis of zymosan in vivo, and antibody blockade of IFN-γ after endotoxemia improved survival of secondary candidemia. Transcriptomic analysis of innate lymphocytes during endotoxemia suggested that NKT cells drove IFN-γ production by NK cells via mTORC1. Activation of invariant NKT (iNKT) cells with glycolipid antigen drove immunosuppression. Deletion of iNKT cells in Cd1d(–/–) mice or inhibition of mTOR by rapamycin reduced immunosuppression and susceptibility to secondary Candida infection. Thus, although rapamycin is typically an immunosuppressive medication, in the context of sepsis, rapamycin has the opposite effect. These results implicated an NKT cell/mTOR/IFN-γ axis in immunosuppression following endotoxemia or sepsis. In summary, in vivo iNKT cells activated mTORC1 in NK cells to produce IFN-γ, which worsened macrophage phagocytosis, clearance of secondary Candida infection, and mortality.

Gaze-tracking techniques have advanced our understanding of visual attention and decision making during walking and athletic events, but little is known about how vision influences behavior during running over common, natural obstacles. This study tested hypotheses about whether runners regularly collect visual information and pre-plan obstacle clearance (feedforward control), make improvisational adjustments (online control), or some combination of both. In this study, the gaze profiles of 5 male and 5 female runners, fitted with a telemetric gaze-tracking device, were used to identify the frequency of fixations on an obstacle during a run. Overall, participants fixated on the obstacle 2.4 times during the run, with the last fixation occurring on average between 40% and 80% of the run, suggesting runners potentially shifted from a feedforward planning strategy to an online control strategy during the late portions of the running trial. A negative association was observed between runner velocity and average number of fixations. Consistent with previous studies on visual strategies used during walking, our results indicate that visual attentiveness is part of an important feedforward strategy for runners allowing them to safely approach an obstacle. Thus, visual obstacle attention is a key factor in the navigation of complex, natural landscapes while running.

Rotational structures have been measured using the Jurogam II and GAMMASPHERE arrays at low spin following the Gd155(α,2n)Dy157 and Nd148(C12,5n)Dy155 reactions at 25 and 65 MeV, respectively. We report high-K bands, which are conjectured to be the first candidates of a Kπ=2+γ vibrational band, built on the [505]11/2− neutron orbital, in both odd-ADy155,157 isotopes. The coupling of the first excited K=0+ states or the so-called β vibrational bands at 661 and 676 keV in Dy154 and Dy156 to the [505]11/2− orbital, to produce a Kπ=11/2− band, was not observed in both Dy155 and Dy157, respectively. The implication of these findings on the interpretation of the first excited 0+ states in the core nuclei Dy154 and Dy156 are also discussed.

Introduction: The lack of rigorous quality standards in pre-clinical radiation dosimetry has renewed interest in the development of anthropomorphic phantoms. Using 3D printing customisable phantoms can be created to assess all parts of pre-clinical radiation research: planning, image guidance and treatment delivery. We present the full methodology, including material development and printing designs, for the production of a high spatial resolution, anatomically realistic heterogeneous small animal phantom. Methods: A methodology for creating and validating tissue equivalent materials is presented. The technique is demonstrated through the development of a bone-equivalent material. This material is used together with a soft-tissue mimicking ABS plastic filament to reproduce the corresponding structure geometries captured from a CT scan of a nude mouse. Air gaps are used to represent the lungs. Phantom validation was performed through comparison of the geometry and X-ray attenuation of CT images of the phantom and animal images. Results: A 6.6% difference in the attenuation of the bone-equivalent material compared to the reference standard in softer beams (0.5 mm Cu HVL) rapidly decreases as the beam is hardened. CT imaging shows accurate (sub-millimetre) reproduction of the skeleton (Distance-To-Agreement 0.5 mm ± 0.4 mm) and body surface (0.7 mm ± 0.5 mm). Histograms of the voxel intensity profile of the phantom demonstrate suitable similarity to those of both the original mouse image and that of a different animal. Conclusions: We present an approach for the efficient production of an anthropomorphic phantom suitable for the quality assurance of pre-clinical radiotherapy. Our design and full methodology are provided as open source to encourage the pre-clinical radiobiology community to adopt a common QA standard.

To test the predictive power of ab initio nuclear structure theory, the lifetime of the second 2(+) state in neutron-rich O-20, tau(2(2)(+)) = 150(-30)(+80) fs, and an estimate for the lifetime of ...

The low-lying energy spectrum of the extremely neutron-deficient self-conjugate (N = Z) nuclide 88 44Ru44 has been measured using the combination of the Advanced Gamma Tracking Array (AGATA) spectrometer, the NEDA and Neutron Wall neutron detector arrays, and the DIAMANT charged particle detector array. Excited states in 88Ru were populated via the 54Fe(36Ar; 2n )88Ru fusion-evaporation reaction at the Grand Acc�el�erateur National d'Ions Lourds (GANIL) accelerator complex. The observed -ray cascade is assigned to 88Ru using clean prompt - -2-neutron coincidences in anti-coincidence with the detection of charged particles, con�rming and extending the previously assigned sequence of low-lying excited states. It is consistent with a moderately deformed rotating system exhibiting a band crossing at a rotational frequency that is significantly higher than standard theoretical predictions with isovector pairing, as well as observations in neighboring N > Z nuclides. The direct observation of such a \delayed" rotational alignment in a deformed N = Z nucleus is in agreement with theoretical predictions related to the presence of strong isoscalar neutron-proton pair correlations.

In the Cretaceous of North America, environmental sensitivity and habitat specialization have been hypothesized to explain the surprisingly restricted geographic ranges of many large-bodied dinosaurs. Understanding the drivers behind this are key to determining broader trends of dinosaur species and community response to climate change under greenhouse conditions. However, previous studies of this question have commonly examined only small components of the paleo-ecosystem or operated without comparison to similar modern systems from which to constrain interpretations. Here we perform a high-resolution multi-taxic δ13C and δ18O study of a Cretaceous coastal floodplain ecosystem, focusing on species interactions and paleotemperature estimation, and compare with similar data from extant systems. Bioapatite δ13C preserves predator-prey offsets between tyrannosaurs and ornithischians (large herbivorous dinosaurs), and between aquatic reptiles and fish. Large ornithischians had broadly overlapping stable isotope ranges, contrary to hypothesized niche partitioning driven by specialization on coastal or inland subhabitat use. Comparisons to a modern analogue coastal floodplain show similar patterns of ecological guild structure and aquatic-terrestrial resource interchange. Multi-taxic oxygen isotope temperature estimations yield results for the Campanian of Alberta (Canada) consistent with the few other paleotemperature proxies available, and are validated when applied for extant species from a modern coastal floodplain, suggesting that this approach is a simple and effective avenue for paleoenvironmental reconstruction. Together, these new data suggest that dinosaur niche partitioning was more complex than previously hypothesized, and provide a framework for future research on dinosaur-dominated Mesozoic floodplain communities.

6 pags., 4 figs., The γ-ray emission from the nuclei Fe following Coulomb excitation at bombarding energy of 400-440 AMeV was measured with special focus on E1 transitions in the energy region 4-8 MeV. The unstable neutron-rich nuclei Fe were produced at the FAIR-GSI laboratories and selected with the FRS spectrometer. The γ decay was detected with AGATA. From the measured γ-ray spectra the summed E1 strength is extracted and compared to microscopic quasi-particle phonon model calculations. The trend of the E1 strength with increasing neutron number is found to be fairly well reproduced with calculations that assume a rather complex structure of the 1 states (three-phonon states) inducing a strong fragmentation of the E1 nuclear response below the neutron binding energy., This work was partially supported by INFN (Italy) and STFC (UK), the Swedish Research Council (Vetenskapsrådet, VR 2010-147, 2011-5253, and 2016-3969), BMBF NuSTAR-AGATA 05P18RDFN9 and BMBF NuSTAR 05P18RDFN1. The project was co-funded by the European Commission under the 7th Framework Program for RTD (2007-2013) under the Capacities Program (Contract Number 262010, ENSAR). This work was par-tially supported by the Ministry of Science, and Generalitat Valenciana, Spain, under the Grants SEV-2014-0398, FPA2017-84756-C4, PROMETEO/2019/005 and by the EU FEDER funds.

The lifetimes of the low-lying excited states 2(+) and 4(+) have been directly measured in the neutron-deficient Sn-106,Sn-108 isotopes. the nuclei were populated via a deep-inelastic reaction and the lifetime measurement was performed employing a differential plunger device. the emitted gamma rays were detected by the AGATA array, while the reaction products were uniquely identified by the VAMOS++ magnetic spectrometer. Large-Scale Shell-Model calculations with realistic forces indicate that, independently of the pairing content of the interaction, the quadrupole force is dominant in the B(E2; 2(1)(+) -> 0(g.s)(+)) values and it describes well the experimental pattern for Sn104-114 ; the B(E2;(+)(4) -> 2(1)(+)) values, measured here for the first time, depend critically on a delicate pairing-quadrupole balance, disclosed by the very precise results in Sn-108. (C) 2020 the Authors. Published by Elsevier B.V., European Union's Seventh Framework Programme for Research and Technological DevelopmentEuropean Union (EU) [262010]; Fondazione Cassa di Risparmio Padova e Rovigo under the project CONPHYT, starting grant in 2017; Swedish Research CouncilSwedish Research Council [822-2005-3332, 821-2010-6024, 821-2013-2304, 621-20145558, 2017-0065]; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation [2005.0184]; Scientific and Technological Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [114F473]; Ministerio de Ciencia e InnovacionInstituto de Salud Carlos IIISpanish Government [SEV-2014-0398, FPA2017-84756-C4, EEBBI-15-09671]; Generalitat ValencianaGeneralitat Valenciana [PROMETEO/2019/005]; EU-FEDER fundsEuropean Union (EU); Croatian Science Foundation [7194]; Hungarian National Research and Innovation Office (NKFIH) [K128947, PD124717, GINOP-2.3.3-15-2016-00034]; Polish National Science Centre under the COPIN-IN2P3 project [2014-14-M-ST2-00738, 2016-22M-ST2-00269, 2017-25-B-ST2-01569]; Polish National Science Centre under the COPIGAL project [2014-14-M-ST2-00738, 2016-22M-ST2-00269, 2017-25-B-ST2-01569]; Polish National Science Centre under the POLITA project [2014-14-M-ST2-00738, 2016-22M-ST2-00269, 2017-25-B-ST2-01569], The authors would like to thank the AGATA and VAMOS collaborations. Special thanks go to the GANIL technical staff for their help in setting up the apparatuses and the good quality beam and to A. Poves for his fruitful comments. This work was partially supported by the European Union's Seventh Framework Programme for Research and Technological Development (grant no. 262010). A.G. acknowledges the support of the Fondazione Cassa di Risparmio Padova e Rovigo under the project CONPHYT, starting grant in 2017. the work was also supported (B.C, H.L., J.N. and U.J.) by Swedish Research Council under the grant agreements nos. 822-2005-3332, 821-2010-6024, 821-2013-2304, 621-20145558 and 2017-0065, and by the Knut and Alice Wallenberg Foundation grant no. 2005.0184, (B.S.) by the Scientific and Technological Council of Turkey (TUBITAK) under the project no. 114F473, (A.G., A.J. and R.P.) by the Ministerio de Ciencia e Innovacion under the contracts nos. SEV-2014-0398, FPA2017-84756-C4 and EEBBI-15-09671, by the Generalitat Valenciana under the grant agreement no. PROMETEO/2019/005 and by the EU-FEDER funds, (T.M and S.S.) by the Croatian Science Foundation under the project no. 7194, (I.K and D.S.) by the Hungarian National Research and Innovation Office (NKFIH) under the project nos. K128947, PD124717 and GINOP-2.3.3-15-2016-00034, (M.P.) by the Polish National Science Centre with the grants nos. 2014-14-M-ST2-00738, 2016-22M-ST2-00269 and 2017-25-B-ST2-01569 under the COPIN-IN2P3, COPIGAL and POLITA projects.

International audience; A first performance test of the Coulomb excitation multipolarimetry (Coulex-multipolarimetry) method is presented. It is based on a $^{85}\hbox {Br}\,\pi p_{3/2}\rightarrow \pi p_{1/2}$ spin-flip experiment performed as part of the PreSPEC-AGATA campaign at the GSI Helmholtzzentrum für Schwerionenforschung (GSI). Via determination of background levels around the expected $^{85}\hbox {Br}$ excitations as well as measured $^{197}\hbox {Au}$ excitations, an upper limit for the M1 transition strength of the $1/2_1^-\rightarrow 3/2_\text {g.s.}^-$ transition in $^{85}\hbox {Br}$ and a lower beam time limit for upcoming experimental campaigns utilizing Coulex-multipolarimetry have been inferred. The impact of the use of AGATA in its anticipated $1\pi $ configuration on these estimates is deduced via Geant4 simulations.

Excited states in the extremely neutron-deficient nucleus $$^{172}{\mathrm {Pt}}$$172Pt were populated via $$^{96}\mathrm {Ru}(^{78}\mathrm {Kr},2p)$$96Ru(78Kr,2p) and $$^{92}\mathrm {Mo}(^{83}\mathrm {Kr},3n)$$92Mo(83Kr,3n) reactions. The level scheme has been extended up to an excitation energy of $$\approx 5~\hbox {MeV}$$≈5MeV and tentative spin-parity assignments up to $$I^\pi = 18^+$$Iπ=18+. Linear polarization and angular distribution measurements were used to determine the electromagnetic E1 character of the dipole transitions connecting the positive-parity ground-state band with an excited side-band, firmly establishing it as a negative-parity band. The lowest member of this negative-parity structure was firmly assigned spin-parity $$3^-$$3-. In addition, we observed an E3 transition from this $$3^-$$3- state to the ground state, providing direct evidence for octupole collectivity in $$^{172}{\mathrm {Pt}}$$172Pt. Large-scale shell model (LSSM) and total Routhian surface (TRS) calculations have been performed, supporting the interpretation of the $$3^-$$3- state as a collective octupole-vibrational state.

Nuclear instruments & methods in physics research / A Accelerators, spectrometers, detectors and associated equipment Section A 969, 163967 (2020). doi:10.1016/j.nima.2020.163967, Published by North-Holland Publ. Co., Amsterdam

The advancement of intracytoplasmic sperm injection (ICSI) has allowed azoospermic men previously deemed infertile to father their own biological offspring provided that sperm can be retrieved from the testicles. Although a number of surgical sperm retrieval techniques can be utilized to obtain sperm for the ICSI cycle, the specific technique used depends on the underlying cause of azoospermia.

Objective: The objective of this study was to evaluate the rising trend in the incidence and mortality of renal cell carcinoma in Ireland. Methods: Data from the National Cancer Registry of Ireland on primary adenocarcinomas of the kidney from 2003 to 2013 were evaluated. Statistical analysis was performed on the data using IBM SPSS statistics V24 software package and Microsoft Excel Software. Results: There were 3801 cases of adenocarcinoma of the kidney with 29% of tumours (n=1103) being found incidentally. The age-adjusted incidence rate of renal cell carcinoma in 2003 was 4.66 per 100,000 women and 8.78 per 100,000 men. These figures have risen to 5.78 and 13.14 in 2013, respectively. There was an annual percentage change of +2.2% for women and +4.1% for men from the years 2003 to 2013. For both sexes the age-standardised all-cause mortality rate for renal adenocarcinoma increased from 1.07 per 100,000 in 2003 to 4.32 ± 0.06 per 100,000 in 2013, an annual percentage change of +15%. Age-adjusted mortality rates in the female population in Ireland increased from 0.78 to 2.66, an annual percentage change of +13.1% and from 1.41 to 6.04 in men, an annual percentage change of +15.8%. Conclusion: There is a paradox emerging in Ireland, with both rising survival rates for renal cell carcinoma and rising mortality rates. While the increased incidence of renal cell carcinoma in Ireland can be attributed somewhat to the increased use of various imaging modalities, it may also be attributed to the significant rise in modifiable risk factors as seen in other developed countries, namely hypertension, obesity, and smoking. Level of evidence: 2c

The Galapagos sea lion ( Zalophus wollebaeki) is an otariid species endemic to the Galapagos archipelago and is currently listed as endangered. The ocular trematode Philophthalmus zalophi was recently reported to affect the survival of juvenile Galapagos sea lions on Santa Cruz Island, resulting in marked ophthalmic changes. This study evaluated the ophthalmic disease and histopathologic effects of P. zalophi on juvenile Galapagos sea lions in the largest rookery located on San Cristóbal Island. Twenty juvenile Galapagos sea lions (10 male and 10 female) were evaluated among five sites in the rookery El Malecón. Ophthalmic examination, including fluorescein staining and evaluation of the adnexa, cornea, and sclera, were performed on each eye. The presence, number, and location of ocular parasites were determined, and parasites were collected for identification. Conjunctival biopsy was performed on 11 animals: 2 that lacked parasites and gross lesions and 9 with both parasites and gross lesions. All parasites collected were confirmed as P. zalophi and identified in 80% (16/20) of the study animals and 70% (28/40) of the examined eyes. Philophthalmus zalophi was most frequently found attached to the nictitating membrane but also located on the palpebral conjunctiva or cornea. The most common clinical signs were varying degrees of conjunctival hyperemia (28/40 eyes), most frequently of the nictitating membrane and mucoid ocular discharge (12/40 eyes). The number of parasites was significantly associated with the degree of conjunctival hyperemia ( P0.001). Histopathology of conjunctival biopsies revealed organized lymphoid follicles and lymphoplasmacytic infiltrates. The histopathologic changes and gross lesions were likely due to the parasite's attachment to the conjunctiva. This study provides additional details of P. zalophi infection in juvenile Galapagos sea lions. Further research is warranted to detail the life cycle of this parasite, transmission to sea lions, and potential treatment protocols.

In 1963, the corporation of the city of Glasgow approved plans for 96 km of motorways. To date, 2017, 48 km have been constructed. These are on a grand scale, with 5 km of dual five-lane, 2 km of dual four-lane and over 25 km of dual three-lane motorways. Traffic flows as high as 198 000 vehicles/d have been recorded. Savings of time, accidents and fuel have been realised as a result. The main focus of this briefing paper is the geometric design of the motorways. Scott Wilson Kirkpatrick and Partners, consulting engineers, were responsible for this work. Much emphasis is placed on motorway traffic volumes. This is because road user benefits are directly related to the amount of traffic diverted to the motorways. Also, predicted traffic was a primary factor in the outline design of the motorways.

Background DNA methylation is a heritable epigenetic mark, enabling stable but reversible gene repression. In mammalian cells, DNA methyltransferases (DNMTs) are responsible for modifying cytosine to 5-methylcytosine (5mC), which can be further oxidized by the TET dioxygenases to ultimately cause DNA demethylation. However, the genome-wide cooperation and functions of these two families of proteins, especially at large under-methylated regions, called canyons, remain largely unknown. Results Here we demonstrate that DNMT3A and TET1 function in a complementary and competitive manner in mouse embryonic stem cells to mediate proper epigenetic landscapes and gene expression. The longer isoform of DNMT3A, DNMT3A1, exhibits significant enrichment at distal promoters and canyon edges, but is excluded from proximal promoters and canyons where TET1 shows prominent binding. Deletion of Tet1 increases DNMT3A1 binding capacity at and around genes with wild-type TET1 binding. However, deletion of Dnmt3a has a minor effect on TET1 binding on chromatin, indicating that TET1 may limit DNA methylation partially by protecting its targets from DNMT3A and establishing boundaries for DNA methylation. Local CpG density may determine their complementary binding patterns and therefore that the methylation landscape is encoded in the DNA sequence. Furthermore, DNMT3A and TET1 impact histone modifications which in turn regulate gene expression. In particular, they regulate Polycomb Repressive Complex 2 (PRC2)-mediated H3K27me3 enrichment to constrain gene expression from bivalent promoters. Conclusions We conclude that DNMT3A and TET1 regulate the epigenome and gene expression at specific targets via their functional interplay. Electronic supplementary material The online version of this article (10.1186/s13059-018-1464-7) contains supplementary material, which is available to authorized users.

Resource efficiency is an instrumental mitigation option in the steel industry but, existing studies have failed to provide a global analysis of the sector's energy and material use. Despite the interactions between energy and materials in steelmaking, recent studies investigate each of these resources in isolation, providing only partial insight into resource efficiency. This study analyses the latest, most comprehensive resource data on the global steel industry and quantifies the savings associated with reducing this through energy- and material-saving measures. Three production routes are investigated for 2010, namely the blast furnace/basic oxygen furnace (ore-based); direct reduction/electric arc furnace; scrap-based electric arc furnace routes (secondary). The sector's resource efficiency – accounting for energy and materials – is expressed in exergy and measured at two levels, that of production routes and plants. The results show that the sector is 32.9% resource-efficient and that secondary steelmaking is twice as efficient (65.7%) as ore-based production (29.1%). Energy-saving options, such as the recovery of off-gases, can save about 4 EJ/year (exergy). Materialsaving options, such as yield improvements, can deliver just under 1 EJ/year extra. A global shift from average ore-based production to best available operation can save up to 6.4 EJ/year; a 26% reduction in global exergy input to steelmaking. Shifting to secondary steelmaking can save 8 EJ/year, limited only by the need to still produce half of steel from ore in 2050. Resource efficiency, measured in exergy, provides stakeholders with an instrument that treats energy and material efficiency measures on an equal footing.

Testicular torsion is the most concerning underlying cause of acute scrotal pain that can lead to loss of the affected testicle. Whether a torted testicle can be salvaged surgically is directly affected by prompt presentation and diagnosis. This study aims to evaluate the awareness of testicular torsion amongst Irish parents and evaluate their response to a potential torsion. An anonymous questionnaire was distributed to parents attending general paediatric clinics and an acute paediatric unit in two paediatric tertiary referral centres. SPSS statistical analysis software was used to perform multivariant analysis of the data. There were 242 completed surveys. Fifty-six percent of responders had an awareness of torsion. In the event of an episode of severe testicular pain parents who were aware of testicular torsion were 4 times more likely to present immediately than those who had no awareness of torsion (OR 4.2, 95% CI 1.4–12.2, P

Training locomotor central pattern-generating networks (CPGs) through arm and leg cycling improves walking in chronic stroke. These outcomes are presumed to result from enhanced interlimb connectivity and CPG function. The extent to which rhythmic arm training activates interlimb CPG networks for locomotion remains unclear and was assessed by studying chronic stroke participants before and after 5 wk of arm cycling training. Strength was assessed bilaterally via maximal voluntary isometric contractions in the legs and hands. Muscle activation during arm cycling and transfer to treadmill walking were assessed in the more affected (MA) and less affected (LA) sides via surface electromyography. Changes to interlimb coupling during rhythmic movement were evaluated using modulation of cutaneous reflexes elicited by electrical stimulation of the superficial radial nerve at the wrist. Bilateral soleus stretch reflexes were elicited at rest and during 1-Hz arm cycling. Clinical function tests assessed walking, balance, and motor function. Results show significant changes in function and neurophysiological integrity. Training increased bilateral grip strength, force during MA plantarflexion, and muscle activation. “Normalization” of cutaneous reflex modulation was found during arm cycling. There was enhanced activity in the dorsiflexor muscles on the MA side during the swing phase of walking. Enhanced interlimb coupling was shown by increased modulation of MA soleus stretch reflex amplitudes during arm cycling after training. Clinical evaluations showed enhanced walking ability and balance. These results are consistent with training-induced changes in CPG function and interlimb connectivity and underscore the need for arm training in the functional rehabilitation of walking after neurotrauma.NEW & NOTEWORTHY It has been suggested but not tested that training the arms may influence rehabilitation of walking due to activation of interneuronal patterning networks after stroke. We show that arm cycling training improves strength, clinical function, coordination of muscle activity during walking, and neurological connectivity between the arms and the legs. The arms can, in fact, give the legs a helping hand in rehabilitation of walking after stroke.

Background Serum interleukin 6 (IL-6), chemokine ligand 2 (CCL2), C-reactive protein (CRP), and the ratio of aspartate transaminase to alanine transaminase (AST:ALT) have been correlated with fibrosis and necroinflammatory activity in humans with various hepatopathies. Hypothesis/objectives To determine whether increases in serum IL-6, CCL2, CRP, or AST:ALT were associated with moderate to severe fibrosis or necroinflammatory activity in dogs with various hepatopathies. Animals Forty-four client-owned dogs with clinical evidence of liver disease and 10 healthy purpose-bred dogs, all undergoing liver biopsies by laparoscopy or laparotomy. Methods Measurement of serum IL-6, CCL2, CRP, AST, and ALT before scheduled liver biopsy and evaluation of liver histopathology using the METAVIR scoring system used in human medicine, blinded to clinical presentation. Results Median serum IL-6 was approximately twice as high in dogs with high fibrosis scores (15.5 pg/mL; range, 1.4 to 235 pg/mL) compared to dogs with low fibrosis scores (7.6 pg/mL; range, 1.4 to 148.1 pg/mL), with marginal significance (P = .05). Median serum CCL2 was significantly higher in dogs with active necroinflammation (444 pg/mL; range, 144 to 896 pg/mL) compared to dogs without detectable necroinflammation (326 pg/mL; range, 59 to 1692 pg/mL; P = .008), but with considerable overlap between groups. Neither serum CRP nor AST:ALT ratios were significantly different based on fibrosis or necroinflammatory scores. Conclusions and clinical importance Because of substantial variability among dogs, single measurements of IL-6 and CCL2 have limited diagnostic utility for identifying fibrosis or necroinflammation, respectively, in dogs with various chronic liver diseases. The value of these biomarkers should be explored further in monitoring response to treatment in individual dogs with chronic hepatopathies.

This project quantified the impact that voluntary reformulation efforts of the food industry had on the Irish population's nutrient intake. Nutrient composition data on reformulated products were collected from 14 major food companies for two years, 2005 and 2012. Probabilistic intake assessments were performed using the Irish national food consumption surveys as dietary intake data. The nutrient data were weighted by market shares replacing existing food composition data for these products. The reformulation efforts assessed, significantly reduced mean energy intakes by up to 12 kcal/d (adults), 15 kcal/d (teens), 19 kcal/d (children) and 9 kcal/d (pre-schoolers). Mean daily fat intakes were reduced by up to 1.3 g/d, 1.3 g/d, 0.9 g/d and 0.6 g/d, saturated fat intakes by up to 1.7 g/d, 2.3 g/d, 1.8 g/d and 1 g/d, sugar intakes by up to 1 g/d, 2 g/d, 3.5 g/d and 1 g/d and sodium intakes by up to 0.6 g/d, 0.5 g/d, 0.2 g/d, 0.3 g/d for adults, teenagers, children and pre-school children, respectively. This model enables to assess the impact of industry reformulation amongst Irish consumers' nutrient intakes, using consumption, food composition and market share data.

Objective:Otitis externa is a common presentation to secondary care otolaryngology clinics. Despite this, few studies have investigated the microbiology and antimicrobial resistance of otitis externa. This study aimed to examine these issues.Methods:Analysis identified 302 swabs taken from 217 patients (100 male, 117 female), between 1 January 2015 and 30 March 2016, at our rapid access otolaryngology clinic.Results:In total, 315 organisms were isolated; the most frequent was Pseudomonas aeruginosa (31.1 per cent), followed by candida species (22.9 per cent) and Staphylococcus aureus (11.7 per cent). P aeruginosa was sensitive to ciprofloxacin in 97.7 per cent of cases and to gentamicin in 78.4 per cent.Conclusion:Compared with studies worldwide, the relative proportions of different organisms causing otitis externa and the patterns of antimicrobial resistance differ. Increasing resistance of P aeruginosa to aminoglycosides demonstrates a changing pattern of antimicrobial resistance that has not been previously reported. Reassuringly, quinolone antibiotics remain highly effective when treating P aeruginosa.

Chemical products are ubiquitous in modern society. The chemical sector is the largest industrial energy consumer and the third largest industrial emitter of carbon dioxide. The current portfolio of mitigation options for the chemical sector emphasizes upstream "supply side" solutions, whereas downstream mitigation options, such as material efficiency, are given comparatively short shrift. Key reasons for this are the scarcity of data on the sector's material flows, and the highly intertwined nature of its complex supply chains. We provide the most up to date, comprehensive and transparent data set available publicly, on virgin production routes in the chemical sector: from fossil fuel feedstocks to chemical products. We map global mass flows for the year 2013 through a complex network of transformation processes, and by taking account of secondary reactants and by-products, we maintain a full mass balance throughout. The resulting data set partially addresses the dearth of publicly available information on the chemical sector's supply chain, and can be used to prioritise downstream mitigation options.

In this study, we examined the cellular distribution of encephalopsin (opsin 3; OPN3) expression in the striatum of non-human primates. In addition, because of our long standing interest in Parkinson's disease and neuroprotection, we examined whether parkinsonian (MPTP; 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) insult and/or photobiomodulation (670 nm) had any impact on encephalopsin expression in this key area of the basal ganglia. Striatal sections of control naïve monkeys, together with those that were either MPTP- and/or photobiomodulation-treated were processed for immunohistochemistry. Our results revealed two populations of striatal interneurones that expressed encephalopsin, one of which was the giant, choline acetyltransferase-containing, cholinergic interneurones. The other population had smaller somata and was not cholinergic. Neither cell group expressed the calcium-binding protein, parvalbumin. There was also rich encephalopsin expression in a set of terminals forming striosome-like patches across the striatum. Finally, we found that neither parkinsonian (MPTP) insult nor photobiomodulation had any effect on encephalopsin expression in the striatum. In summary, our results revealed an extensive network of encephalopsin containing structures throughout the striatum, indicating that external light is in a position to influence a range of striatal activities at both the interneurone and striosome level.

Equine serum hepatitis (i.e., Theiler’s disease) is a serious and often life-threatening disease of unknown etiology that affects horses. A horse in Nebraska, USA, with serum hepatitis died 65 days after treatment with equine-origin tetanus antitoxin. We identified an unknown parvovirus in serum and liver of the dead horse and in the administered antitoxin. The equine parvovirus-hepatitis (EqPV-H) shares

Basal cell carcinoma is the most commonly occurring cancer worldwide but it is rarely seen in non-sun-exposed areas of the body such as the scrotum.1 Basal cell carcinomas account for 5–10% of all scrotal tumours.2,3 Scrotal basal cell carcinoma is considered more aggressive with higher rates of metastasis versus non-scrotal basal cell carcinoma.1 Gorlin syndrome or nevoid basal cell carcinoma syndrome is an autosomal dominant condition characterised by the development of multiple basal cell carcinomas at a young age.4,5 Prevalence of nevoid basal cell carcinoma syndrome is reported to range from 1 in 57,000 to 1 in 164,000.5 We present the case of a 58-year-old gentleman with a 3-month history of bleeding scrotal and penile lesions. These lesions were excised with 2 cm margins and without complication. Histology showed surface ulceration with basaloid infiltrating tumour extending into the dermis. Given the potential for a very high rate of tumour occurrence within individuals, surgical management of basal cell carcinomas can result in significant, lifestyle-limiting disfigurement.5 As understanding of the pathogenesis of nevoid basal cell carcinoma syndrome has advanced, a number of targeted therapies have been developed.5 Vismodegib targets the Hedgehog signalling pathway and is used in the treatment of locally advanced and metastatic basal cell carcinomas. This represents a rare case of basal cell carcinoma of the scrotum associated with nevoid basal cell carcinoma syndrome caused by a de novo mutation. It is not clear from the literature whether incidence of scrotal tumours is increased in Gorlin syndrome but given the increased risk of basal cell carcinoma elsewhere, it may be prudent for those with known Gorlin syndrome to regularly examine the scrotal skin along with recommended frequent dermatologic surveillance. Level of evidence: 5.

Barriers in acquiring, maintaining, and generalizing daily living skills are factors that contribute to discrepancies in independent living outcomes among transition age youth and young adults with intellectual and developmental disabilities (IDD). Acquisition and generalization of daily living skills empowers transition age youth and young adults with disabilities to meet their own needs with minimal reliance on others. Infusing the use of technology as a self-prompting device facilitates the acquisition of tasks that may not be otherwise attainable. In this study, self-directed video prompting on an iPad with the My Pictures Talk application was used to help young adults with IDD in a postsecondary program acquire daily living skills in a single subject, multiple probe across subjects design. The effects of the intervention on generalization to tasks that were one, two, and three components different were also assessed. Results demonstrated a functional relationship between the introduction of the intervention and improvement in skill performance.

Troodontid material from the Maastrichtian of North America is extremely rare, beyond isolated teeth from microvertebrate sites. Here we describe troodontid frontals from the early Maastrichtian Horseshoe Canyon Formation (Horsethief Member). The most complete specimen, TMP 1993.105.0001, is notably foreshortened and robust when compared with numerous specimens referred to Troodon from the Dinosaur Park Formation, and exhibits several characteristics that distinguish it from other Late Cretaceous troodontids. Morphometric analyses reinforce shape differences between TMP 1993.105.0001 and other North American troodontids, and show that proportional differences are independent of size. We therefore erect a new taxon, Albertavenator curriei gen. et sp. nov., which is diagnosed by the following autapomorphies: (1) primary supraciliary foramen is truncated anteriorly by the lacrimal contact; (2) superficial (ectocranial) surface of the frontal proportionally shorter than all known troodontids, with a length to width ratio under 1.3; and (3) frontoparietal contact in which an enlarged lappet of the frontal extends medially to extensively overlap the lateral region of the anteromedial process of the parietal. Interestingly, tooth and jaw morphology from the single relatively complete dentary recovered from the Horseshoe Canyon cannot be distinguished from dentaries and teeth from the Dinosaur Park Formation. If the dentary and teeth from the Horsethief Member of the Horseshoe Canyon Formation prove to belong to A. curriei, extensive overlap in tooth morphology between the Dinosaur Park and Horseshoe Canyon formations reinforces the notion that tooth morphotypes do not exhibit strong correspondence to species alpha diversity, and may encompass multiple closely related taxa.

In this study, we explored the effects of a longer term application, up to 12 weeks, of photobiomodulation in normal, naïve macaque monkeys. Monkeys (n = 5) were implanted intracranially with an optical fibre device delivering photobiomodulation (red light, 670 nm) to a midline midbrain region. Animals were then aldehyde-fixed and their brains were processed for immunohistochemistry. In general, our results showed that longer term intracranial application of photobiomodulation had no adverse effects on the surrounding brain parenchyma or on the nearby dopaminergic cell system. We found no evidence for photobiomodulation generating an inflammatory glial response or neuronal degeneration near the implant site; further, photobiomodulation did not induce an abnormal activation or mitochondrial stress in nearby cells, nor did it cause an abnormal arrangement of the surrounding vasculature (endothelial basement membrane). Finally, because of our interest in Parkinson's disease, we noted that photobiomodulation had no impact on the number of midbrain dopaminergic cells and the density of their terminations in the striatum. In summary, we found no histological basis for any major biosafety concerns associated with photobiomodulation delivered by our intracranial approach and our findings set a key template for progress onto clinical trial on patients with Parkinson's disease.

New York City rats provide a gift to virologists Despite the development of curative drugs for hepatitis C virus (HCV) infection, global eradication of HCV will likely require a prophylactic vaccine. Progress toward a vaccine has been impeded by the absence of mouse models suitable for studying the immune response to HCV. Billerbeck et al. found that a HCV-related virus isolated from New York City rats produces an infection in laboratory mice that shares several immunological features with human infections (see the Perspective by Klenerman and Barnes). Their initial analyses of the infected mice revealed that acute clearance of the virus was dependent on T cells but not on natural killer cells. Science , this issue p. 204 ; see also p. 129

The Refugio Oil Spill occurred on May 19, 2015, due to the failure of an underground pipeline, owned and operated by a subsidiary of Plains All-American Pipeline near Highway 101 in Santa Barbara County. The Responsible Party initially estimated the amount of crude oil released at about 104,000 gallons, with 21,000 gallons reaching the ocean. A Unified Command (UC) was established consisting of Incident Commanders from the U.S. Coast Guard (USCG), California Department of Fish and Wildlife (CDFW) Office of Spill Prevention and Response (OSPR), Santa Barbara County, and Plains Pipeline with additional participation by the U.S. Environmental Protection Agency and California State Parks. Within hours, the CDFW closed fisheries and the following day Governor Brown declared a state of emergency for Santa Barbara County. The released oil caused heavy oiling of both on and offshore areas at Refugio State Beach and impacted other areas of Santa Barbara and Ventura. A number of factors created unique challenges for the management of this response. In addition to direct natural resource impacts, the closure of beaches and fisheries occurred days before the Memorial Day weekend resulting in losses for local businesses and lost opportunities for the public. The Santa Barbara community, with its history with oil spills and environmental activism, was extremely concerned and interested in involvement, including the use of volunteers on beaches. Also this area of the coast has significant tribal and archeologic resources that required sensitive handling and coordination. Finally, this area of California’s coast is a known natural seep area which created the need to distinguish spilled from ‘naturally occurring’ oil. Most emergency responses, including oil spills, follow a similar pattern of command establishment, response and cleanup phases, followed by non-response phase monitoring, cleanup and restoration. This paper will analyze the Refugio oil spill response in three primary focus areas: 1) identify the ways in which this spill response was unique and required innovative and novel solutions; 2) identify the ways in which this response benefited from the ‘lessons’ learned from both the Deepwater Horizon and Cosco Busan oil spills; and 3) provide a summary of OSPR’s response evaluation report for Refugio, with specific focus on how the lessons learned and best practices will inform future planning efforts within California.

Global annual resource use reached nearly 90 billion metric tons in 2017 and may more than double by 2050. This growth is coupled with a shift of materials extraction from Europe and North America to Asia. In 2017, 60% of all materials were extracted in Asia, and extraction is expected to rise substantially in Africa over the next decade. Local extraction and processing helps to improve standards of living in the developing world, but also leads to important environmental concerns. Globally, materials production and consumption is coming up against environmental constraints in almost every domain, including species biodiversity, land-use change, climate impacts, and biogeochemical flows. Mitigating the impact of materials use is urgent and complex, necessitates proactive assessment of unintended consequences, and requires multidisciplinary systems approaches.