Development of a semi-quantitative scoring protocol for gill lesion assessment in greenlip abalone Haliotis laevigata held at elevated water temperature.

Water temperatures that exceed thermal optimal ranges (~19 to 22°C for greenlip abalone Haliotis laevigata, depending on stock genetics) can be associated with abalone mortalities. We assessed histopathological changes in H. laevigata gills held in control (22°C) or elevated (25°C) water temperature conditions for 47 d by developing a new scoring protocol that incorporates histopathological descriptions and relative score summary. Lesions were allocated to 1 of 3 reaction patterns, (1) epithelial, (2) circulatory or (3) inflammatory, and scored based on their prevalence in gill leaflets. Indices for each reaction pattern were calculated and combined to provide an overall gill index. H. laevigata held in 25°C water temperature had significantly more epithelial lifting and hemolymph channel enlargement and significantly higher gill and circulatory reaction pattern indices than H. laevigata held in 22°C water temperature. One H. laevigata had a proliferation of unidentified cells in the v-shaped skeletal rod of a gill leaflet. The unidentified cells contained enlarged nuclei, a greater nucleus:cytoplasm ratio and, in some cases, mitotic figures. This cell population could represent a region of hematopoiesis in response to hemocyte loss or migration to a lesion. Without thorough diagnostic testing, the origin of these larger cells cannot be confirmed. The new scoring protocol developed will allow the standard quantification of gill lesions for H. laevigata, specifically for heat-related conditions, and could further be adapted for other Haliotis spp.

A seafood risk tool for assessing and mitigating chemical and pathogen hazards in the aquaculture supply chain.

Intricate links between aquatic animals and their environment expose them to chemical and pathogenic hazards, which can disrupt seafood supply. Here we outline a risk schema for assessing potential impacts of chemical and microbial hazards on discrete subsectors of aquaculture-and control measures that may protect supply. As national governments develop strategies to achieve volumetric expansion in seafood production from aquaculture to meet increasing demand, we propose an urgent need for simultaneous focus on controlling those hazards that limit its production, harvesting, processing, trade and safe consumption. Policies aligning national and international water quality control measures for minimizing interaction with, and impact of, hazards on seafood supply will be critical as consumers increasingly rely on the aquaculture sector to supply safe, nutritious and healthy diets.

Next generation Fc scaffold for multispecific antibodies.

Bispecific antibodies (Bispecifics) demonstrate exceptional clinical potential to address some of the most complex diseases. However, Bispecific production in a single cell often requires the correct pairing of multiple polypeptide chains for desired assembly. This is a considerable hurdle that hinders the development of many immunoglobulin G (IgG)-like bispecific formats. Our approach focuses on the rational engineering of charged residues to facilitate the chain pairing of distinct heavy chains (HC). Here, we deploy structure-guided protein design to engineer charge pair mutations (CPMs) placed in the CH3-CH3' interface of the fragment crystallizable (Fc) region of an antibody (Ab) to correctly steer heavy chain pairing. When used in combination with our stable effector functionless 2 (SEFL2.2) technology, we observed high pairing efficiency without significant losses in expression yields. Furthermore, we investigate the relationship between CPMs and the sequence diversity in the parental antibodies, proposing a rational strategy to deploy these engineering technologies.

Self-reported Dysphagia and Pharyngeal Volume Following Whiplash Injury.

Difficulty swallowing has been reported following whiplash injury; however, the reasons remain poorly understood. A possible factor may be the observed changes in pharyngeal volume. The current exploratory study was designed to examine the prevalence of self-reported dysphagia after whiplash and the relationship with recovery status and change in pharyngeal volume. Data were available from a longitudinal study of adults with whiplash. Data included magnetic resonance imaging (MRI) of the cervical spine, the Dysphagia Handicap Index (DHI), and Neck Disability Index (NDI) collected over four timepoints (< 1 week, 2 weeks, 3 months, and 12 months post-injury). Initial cross-sectional analysis examined 60 patients with DHI data from at least one timepoint. A second, longitudinal analysis was conducted on 31 participants with MRI, NDI, and DHI data at both early (< 1-2 weeks) and late (3-12 months) timepoints. The pharynx was contoured on axial T2-weighted MRI slices using OsiriX image processing software and pharyngeal volume (mm3) was quantified. In the 60-patient cohort, prevalence of self-reported dysphagia (DHI ≥ 3) was observed in 50% of participants at least once in 12 months (M = 4.9, SD 8.16, range 0-40). In the longitudinal cohort (n = 31), mean total DHI significantly (p = 0.006) increased between early and late stages. There was no relationship (p = 1.0) between dysphagia and recovery status, per the NDI% score. Pharyngeal volume remained stable and there was no relationship between dysphagia and pharyngeal volume change (p = 1.0). This exploratory study supports the need for further work to understand the nature of dysphagia, extent of functional compromise, and the underlying pathophysiology post-whiplash.

Whiplash-Associated Dysphagia and Dysphonia: A Scoping Review.

Swallowing and voice complaints after a whiplash injury have been observed and reported in several studies; however, variability in study design complicates current understanding of whether dysphagia and dysphonia should be recognised as potential adverse outcomes. A scoping review was conducted across six databases from 1950 to March 2019. A total of 18 studies were included for review. Data regarding study purpose, design, outcome measures, participant characteristics and outcomes reported were extracted. Level of evidence (LOE) was assessed by the American Speech-Language Language Association (ASHA)'s LOE system. All studies were exploratory, with 68% rated as poor (< 3) on quality ratings. Nearly half (n = 6) were single case reports. Only three studies investigated some type of swallow-related outcome specifically within the study aim/s. Incidence of swallow-related problems ranged from 2 to 29%, with unspecified complaints of "swallowing difficulty", "dysphagia" and fatigue and pain whilst chewing reported. Neither swallowing biomechanics nor the underlying pathophysiology of swallow or voice complaints was investigated in any study. Four case studies presented post-whiplash voice complaints; two of which described loss of pitch range. Others described hoarseness, loss of control and weak phonation. Most studies only mentioned swallow- or voice-related deficits when reporting a wider set of post-injury symptomatology and six did not describe the outcome measure used to identify the swallow and voice-related problems reported. The existing literature is limited and of low quality, contributing to an unclear picture of the true incidence and underlying mechanisms of whiplash-related dysphagia and dysphonia.

Responsiveness of the EAT-10 to Clinical Change in Head and Neck Cancer Patients with Dysphagia.

Purpose: This retrospective study evaluated the external responsiveness of the Eating Assessment Tool-10 (EAT-10) to clinical changes in a single cohort (n = 105) treated with chemoradiotherapy (CRT) or radiotherapy (RT) for head-and-neck cancer.Method: Patients completed the EAT-10 four times: (I) Within two weeks of commencing (C)RT, (II) in the final week of (C)RT, (III) two weeks post-(C)RT and (IV) following discharge from speech-language pathology services. Data was compared to their oral intake status, using the Functional Oral Intake Scale (FOIS).Result: Using Cohen's d, changes in the EAT-10 and FOIS were comparable, however, a difference was observed at data-point IV. At data-points I, II and III, the EAT-10 had a strong negative correlation with the FOIS (Spearman's ρ= -0.81, -0.80 and -0.81 resp.). At data-point IV the correlation strength decreased (Spearman's ρ= -0.69). Fisher's Z transformation found no statistically significant correlation coefficient differences between data-points I, II and III. A significant difference in correlation was found between these data-points and data-point IV (p = 0.027; p = 0.039 and p = 0.022 resp.). A very high internal consistency was found (Cronbach's α > 0.95) for all data-points.Conclusion: This study's results indicate that the EAT-10 has weaknesses in the external responsiveness and has redundancy of its question items.

Whiplash-Associated Dysphagia: Considerations of Potential Incidence and Mechanisms.

Non-specific self-reports of dysphagia have been described in people with whiplash-associated disorders (WAD) following motor vehicle collision (MVC); however, incidence and mechanistic drivers remain poorly understood. Alterations in oropharyngeal dimensions on magnetic resonance imaging (MRI), along with heightened levels of stress, pain, and changes in stress-dependent microRNA expression (e.g., miR-320a) have been also associated with WAD, suggesting multi-factorial issues may underpin any potential swallowing changes. In this exploratory paper, we examine key biopsychosocial parameters in three patients with persistent WAD reporting swallowing change and three nominating full recovery after whiplash with no reported swallowing change. Parameters included (1) oropharyngeal volume with 3D MRI, (2) peritraumatic miR-320a expression, and (3) psychological distress. These factors were explored to highlight the complexity of patient presentation and propose future considerations in relation to a potential deglutition disorder following WAD. The three participants reporting changes in swallowing all had smaller oropharyngeal volumes at < 1 week and at 3 months post injury and lower levels of peritraumatic miR-320a. At 3 months post MVC, oropharyngeal volumes between groups indicated a large effect size (Hedge's g = 0.96). Higher levels of distress were reported at both time points for those with persistent symptomatology, including self-reported dysphagia, however, this was not featured in those nominating recovery. This paper considers current evidence for dysphagia as a potentially under-recognized feature of WAD and highlights the need for future, larger-scaled, multidimensional investigation into the incidence and mechanisms of whiplash-associated dysphagia.

Effect of fiber source and particle size on chick performance and nutrient utilization.

The addition of fiber in chick feeds is known to dilute nutrients; as a result, this may reduce nutrient digestibility and performance. However, recent studies suggest that moderate inclusion of insoluble fibers (2 to 3%) may stimulate gizzard development, which could result in better nutrient utilization and chick growth. The previous fiber sources evaluated were subject to wide fluctuation in their nutritional and chemical composition due to variation in processing. Miscanthus giganteus is a C4 grass purposefully grown for its fiber content which has a consistent fiber composition compared to food process residues. The objectives of this study were to determine the effect of dietary fiber source and particle size on day-old chick performance and nutrient digestibility. Day-old chicks (8 chicks per cage, 5 cages per treatment) were fed diets containing 3% of either sepiolite (SEP), cellulose (CEL), coarse beet pulp (BP), fine BP, coarse Miscanthus grass (MG), and fine MG. At the end of days 7, 14, and 21, chicks and experimental diets were weighed to compute average daily gain and feed intake. In addition, excreta from the previous 48 h of each data capture point was collected to determine nutrient digestibility. In general, chicks fed diets containing fiber consumed more feed, gained more weight, and had better feed conversion rate than birds fed the SEP diet. Particle size of the fiber had no effect on chick performance; however, nutrient utilization was higher (P < 0.05) for chicks fed coarse fiber particles compared to these fed fine fiber particles. Birds fed diets containing MG performed similar to chicks fed CEL (P > 0.05), but digestibility coefficients of birds fed BP diets were generally higher than chicks fed MG diets. In conclusion, chicks performed better with fiber in their diet and MG was comparable to CEL.

Native and Denaturing MS Protein Deconvolution for Biopharma: Monoclonal Antibodies and Antibody-Drug Conjugates to Polydisperse Membrane Proteins and Beyond.

Electrospray ionization mass spectrometry (ESI-MS) is a ubiquitously used analytical method applied across multiple departments in biopharma, ranging from early research discovery to process development. Accurate, efficient, and consistent protein MS spectral deconvolution across multiple instrument and detector platforms (time-of-flight, Orbitrap, Fourier-transform ion cyclotron resonance) is essential. When proteins are ionized during the ESI process, a distribution of consecutive multiply charged ions are observed on the m/z scale, either positive [M + nH]n+ or negative [M - nH]n- depending on the ionization polarity. The manual calculation of the neutral molecular weight (MW) of single proteins measured by ESI-MS is simple; however, algorithmic deconvolution is required for more complex protein mixtures to derive accurate MWs. Multiple deconvolution algorithms have evolved over the past two decades, all of which have their advantages and disadvantages, in terms of speed, user-input parameters (or ideally lack thereof), and whether they perform optimally on proteins analyzed under denatured or native-MS and solution conditions. Herein, we describe the utility of a parsimonious deconvolution algorithm (explaining the observed spectra with a minimum number of masses) to process a wide range of highly diverse biopharma relevant and research grade proteins and complexes (PEG-GCSF; an IgG1k; IgG1- and IgG2-biotin covalent conjugates; the membrane protein complex AqpZ; a highly polydisperse empty MSP1D1 nanodisc and the tetradecameric chaperone protein complex GroEL) analyzed under native-MS, denaturing LC-MS, and positive and negative modes of ionization, using multiple instruments and therefore multiple data formats. The implementation of a comb filter and peak sharpening option is also demonstrated to be highly effective for deconvolution of highly polydisperse and enhanced separation of a low level lysine glycation post-translational modification (+162.1 Da), partially processed heavy chain lysine residues (+128.1 Da), and loss of N-acetylglucosamine (GlcNAc; -203.1 Da).

Anti-obesity effects of GIPR antagonists alone and in combination with GLP-1R agonists in preclinical models.

Glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) has been identified in multiple genome-wide association studies (GWAS) as a contributor to obesity, and GIPR knockout mice are protected against diet-induced obesity (DIO). On the basis of this genetic evidence, we developed anti-GIPR antagonistic antibodies as a potential therapeutic strategy for the treatment of obesity and observed that a mouse anti-murine GIPR antibody (muGIPR-Ab) protected against body weight gain, improved multiple metabolic parameters, and was associated with reduced food intake and resting respiratory exchange ratio (RER) in DIO mice. We replicated these results in obese nonhuman primates (NHPs) using an anti-human GIPR antibody (hGIPR-Ab) and found that weight loss was more pronounced than in mice. In addition, we observed enhanced weight loss in DIO mice and NHPs when anti-GIPR antibodies were codosed with glucagon-like peptide-1 receptor (GLP-1R) agonists. Mechanistic and crystallographic studies demonstrated that hGIPR-Ab displaced GIP and bound to GIPR using the same conserved hydrophobic residues as GIP. Further, using a conditional knockout mouse model, we excluded the role of GIPR in pancreatic ß-cells in the regulation of body weight and response to GIPR antagonism. In conclusion, these data provide preclinical validation of a therapeutic approach to treat obesity with anti-GIPR antibodies.

Kinetic studies of C1 and C2 Criegee intermediates with SO2 using laser flash photolysis coupled with photoionization mass spectrometry and time resolved UV absorption spectroscopy.

Recent, direct studies have shown that several reactions of stabilized Criegee intermediates (SCI) are significantly faster than indicated by earlier indirect measurements. The reaction of SCI with SO2 may contribute to atmospheric sulfate production, but there are uncertainties in the mechanism of the reaction of the C1 Criegee intermediate, CH2OO, with SO2. The reactions of C1, CH2OO, and C2, CH3CHOO, Criegee intermediates with SO2 have been studied by generating stabilized Criegee intermediates by laser flash photolysis (LFP) of RI2/O2 (R = CH2 or CH3CH) mixtures with the reactions being followed by photoionization mass spectrometry (PIMS). PIMS has been used to determine the rate coefficient for the reaction of CH3CHI with O2, k = (8.6 ± 2.2) × 10-12 cm3 molecule-1 s-1 at 295 K and 2 Torr (He). The yield of the C2 Criegee intermediate under these conditions is 0.86 ± 0.11. All errors in the abstract are a combination of statistical at the 1σ level and an estimated systematic contribution. For the CH2OO + SO2 reaction, additional LFP experiments were performed monitoring CH2OO by time-resolved broadband UV absorption spectroscopy (TRUVAS). The following rate coefficients have been determined at room temperature ((295 ± 2) K):CH2OO + SO2: k = (3.74 ± 0.43) × 10-11 cm3 molecule-1 s-1 (LFP/PIMS),k = (3.87 ± 0.45) × 10-11 cm3 molecule-1 s-1 (LFP/TRUVAS)CH3CHOO + SO2: k = (1.7 ± 0.3) × 10-11 cm3 molecule-1 s-1 (LFP/PIMS)LFP/PIMS also allows for the direction observation of CH3CHO production from the reaction of CH3CHOO with SO2, suggesting that SO3 is the co-product. For the reaction of CH2OO with SO2 there is no evidence of any variation in reaction mechanism with [SO2] as had been suggested in an earlier publication (Chhantyal-Pun et al., Phys. Chem. Chem. Phys., 2015, 17, 3617). A mean value of k = (3.76 ± 0.14) × 10-11 cm3 molecule-1 s-1 for the CH2OO + SO2 reaction is recommended from this and previous studies. The atmospheric implications of the results are briefly discussed.

Discovery, characterization, and remediation of a C-terminal Fc-extension in proteins expressed in CHO cells.

Protein-based biotherapeutics are produced in engineered cells through complex processes and may contain a wide variety of variants and post-translational modifications that must be monitored or controlled to ensure product quality. Recently, a low level (~1-5%) impurity was observed in a number of proteins derived from stably transfected Chinese hamster ovary (CHO) cells using mass spectrometry. These molecules include antibodies and Fc fusion proteins where Fc is on the C-terminus of the construct. By liquid chromatography-mass spectrometry (LC-MS), the impurity was found to be ~1177 Da larger than the expected mass. After tryptic digestion and analysis by LC-MS/MS, the impurity was localized to the C-terminus of Fc in the form of an Fc sequence extension. Targeted higher-energy collision dissociation was performed using various normalized collision energies (NCE) on two charge states of the extended peptide, resulting in nearly complete fragment ion coverage. The amino acid sequence, SLSLSPEAEAASASELFQ, obtained by the de novo sequencing effort matches a portion of the vector sequence used in the transfection of the CHO cells, specifically in the promoter region of the selection cassette downstream of the protein coding sequence. The modification was the result of an unexpected splicing event, caused by the resemblance of the commonly used GGU codon of the C-terminal glycine to a consensus splicing donor. Three alternative codons for glycine were tested to alleviate the modification, and all were found to completely eliminate the undesirable C-terminal extension, thus improving product quality.

Serological evidence of widespread exposure of Grenada fruit bats to chikungunya virus.

Antibody detection against selected potentially zoonotic vector-borne alphaviruses and flaviviruses was conducted on sera from bats from all six parishes in Grenada, West Indies. Sera were tested for (i) antibodies to flaviviruses West Nile virus, St. Louis encephalitis virus, Ilhéus virus, Bussuquara virus (BSQV), Rio Bravo virus and all four serotypes of dengue virus (DENV) by plaque reduction neutralization test (PRNT); (ii) antibodies to alphaviruses western equine encephalitis virus, Venezuelan equine encephalitis virus and eastern equine encephalitis virus by epitope-blocking enzyme-linked immunosorbent assay (ELISA); and (iii) antibodies to the alphavirus chikungunya (CHIKV) by PRNT. Two species of fruit bats were sampled, Artibeus jamaicensis and Artibeus lituratus, all roosting in or within 1,000 m of human settlements. Fifteen (36%) of the 42 bats tested for neutralizing antibodies to CHIKV were positive. The CHIKV-seropositive bats lived in localities spanning five of the six parishes. All 43 bats tested for epitope-blocking ELISA antibody to the other alphaviruses were negative, except one positive for Venezuelan equine encephalitis virus. All 50 bats tested for neutralizing antibody to flaviviruses were negative, except one that had a BSQV PRNT80 titre of 20. The CHIKV serology results indicate that bats living close to and within human settlements were exposed to CHIKV in multiple locations. Importantly, bats for this study were trapped a year after the introduction and peak of the human CHIKV epidemic in Grenada. Thus, our data indicate that bats were exposed to CHIKV possibly during a time of marked decline in human cases.

Emergence of carp edema virus (CEV) and its significance to European common carp and koi Cyprinus carpio.

Carp edema virus disease (CEVD), also known as koi sleepy disease, is caused by a poxvirus associated with outbreaks of clinical disease in koi and common carp Cyprinus carpio. Originally characterised in Japan in the 1970s, international trade in koi has led to the spread of CEV, although the first recognised outbreak of the disease outside of Japan was not reported until 1996 in the USA. In Europe, the disease was first recognised in 2009 and, as detection and diagnosis have improved, more EU member states have reported CEV associated with disease outbreaks. Although the structure of the CEV genome is not yet elucidated, molecular epidemiology studies have suggested distinct geographical populations of CEV infecting both koi and common carp. Detection and identification of cases of CEVD in common carp were unreliable using the original PCR primers. New primers for conventional and quantitative PCR (qPCR) have been designed that improve detection, and their sequences are provided in this paper. The qPCR primers have successfully detected CEV DNA in archive material from investigations of unexplained carp mortalities conducted >15 yr ago. Improvement in disease management and control is possible, and the principles of biosecurity, good health management and disease surveillance, applied to koi herpesvirus disease, can be equally applied to CEVD. However, further research studies are needed to fill the knowledge gaps in the disease pathogenesis and epidemiology that, currently, prevent an accurate assessment of the likely impact of CEVD on European koi and common carp aquaculture and on wild carp stocks.

High-resolution mass spectrometry confirms the presence of a hydroxyproline (Hyp) post-translational modification in the GGGGP linker of an Fc-fusion protein.

Flexible and protease resistant (G4S)n linkers are used extensively in protein engineering to connect various protein domains. Recently, several groups have observed xylose-based O-glycosylation at linker Ser residues that yield unwanted heterogeneity and may affect product quality. Because of this, an engineering effort was implemented to explore different linker sequence constructs. Here, we demonstrate the presence of an unexpected hydroxylation of a prolyl residue in the linker, made possible through the use of high-resolution mass spectrometry (HR-MS) and MSn. The discovery started with the detection of a poorly resolved ∼+17 Da mass addition at the reduced protein chain level of an Fc-fusion construct by liquid chromatography-MS. Upon further investigation at the peptide level using HR-MS, the mass increase was determined to be +15.99 Da and was localized to the linker peptide SLSLSPGGGGGPAR [210-223]. This peptide corresponds to the C-terminus of Fc [210-216], the G4P linker [217-221], and first 2 amino acids of a growth factor [222-223]. The linker peptide was first subjected to MS2 with collision-induced dissociation (CID) activation. The fragmentation profile localized the modification to the GGGPA [218-222] portion of the peptide. Accurate mass measurement indicated that the modification is an addition of an oxygen and cannot be CH4, thus eliminating several possibilities such as Pro→Leu. However, other possibilities cannot be ruled out. Higher-energy collision-induced dissociation (HCD)-MS2 and MS3 using CID/CID were both unable to differentiate between Ala222→ Ser222 or Pro221→ Hyp221. Finally, MS3 using high-resolution CID/HCD confirmed the mass increase to be a Pro221→Hyp221 post-translational modification.

Carp edema virus in Polish aquaculture - evidence of significant sequence divergence and a new lineage in common carp Cyprinus carpio (L.).

Fish samples initially collected by local veterinarians on the common and koi carp farms in Poland between 2013 and 2015 as part of a KHV surveillance programme, when the water temperature was between 16 and 26 °C, and were also tested for CEV by qPCR. A partial 478 nucleotide fragment of the 4a gene was subsequently generated from 17 qPCR-positive common carp Cyprinus carpio samples from 36 farm sites tested during the period. Sequence alignments and analysis revealed the presence of CEV in Poland both in common carp as well as in koi carp farms, and phylogenetic analysis assigned the Polish CEV sequences into three distinct genogroups. A lineage which includes the original sequences obtained from koi carp in Japan (genogroup II) included sequences from both koi carp and common carp, and the second lineage (genogroup I) contained sequences from common carp only. A third lineage (genogroup III) which was more closely related to the genogroup II also consisted of sequences from common carp only. The latter represents a lineage of CEV not previously described in the literature.

Outcomes of Endovascular Aortic Aneurysm Repair in Kidney Transplant Recipients: Results From a National Quality Initiative.

Contrast-induced nephropathy after endovascular aortic aneurysm repair (EVAR) in kidney transplant recipients (KTRs) can have devastating consequences. The Vascular Quality Initiative (VQI) database was queried to select all KTRs who underwent EVAR between January 2003 and December 2014. Our primary outcome was renal dysfunction, defined as acute kidney injury (AKI; elevation of serum creatinine >0.5 mg/dL from baseline) or new postoperative hemodialysis requirement. Within the EVAR VQI dataset, 40 patients were KTRs (40 of 17 213, or 0.2%). Renal dysfunction occurred in five of 40 patients in the KTR group in comparison to 779 of 17 173 patients in the nontransplanted group (12.5% versus 4.5%, p < 0.01). Emergent EVAR was required in 2 (5%) patients, one of whom required dialysis after surgery and subsequently died. One-year survival after EVAR was similar in the two groups (92.9% versus 93.1%, p = 0.73). KTRs who developed renal dysfunction had significantly lower preoperative estimated glomerular filtration rates (eGFRs) (29.5 versus 54.7, p = 0.007) and a significantly higher iodine:eGFR ratio (0.78 versus 0.39, p = 0.02) despite receiving a similar volume of contrast (70.0 versus 68.8, p = 0.97). Renal dysfunction is 3 times more frequent in KTRs treated with EVAR, though overall survival did not differ between the groups. Decreased preoperative eGFR and a higher iodine:eGFR ratio are associated with postoperative renal dysfunction.

Predicting future uncertainty constraints on global warming projections.

Projections of global mean temperature changes (ΔT) in the future are associated with intrinsic uncertainties. Much climate policy discourse has been guided by "current knowledge" of the ΔTs uncertainty, ignoring the likely future reductions of the uncertainty, because a mechanism for predicting these reductions is lacking. By using simulations of Global Climate Models from the Coupled Model Intercomparison Project Phase 5 ensemble as pseudo past and future observations, we estimate how fast and in what way the uncertainties of ΔT can decline when the current observation network of surface air temperature is maintained. At least in the world of pseudo observations under the Representative Concentration Pathways (RCPs), we can drastically reduce more than 50% of the ΔTs uncertainty in the 2040 s by 2029, and more than 60% of the ΔTs uncertainty in the 2090 s by 2049. Under the highest forcing scenario of RCPs, we can predict the true timing of passing the 2 °C (3 °C) warming threshold 20 (30) years in advance with errors less than 10 years. These results demonstrate potential for sequential decision-making strategies to take advantage of future progress in understanding of anthropogenic climate change.

(Ag,Cu)-Ta-O ternaries as high-temperature solid-lubricant coatings.

Ternary oxides have gained increasing attention due to their potential use as solid lubricants at elevated temperatures. In this work, the tribological properties of three ternary oxides-AgTaO3, CuTaO3, and CuTa2O6-were studied using a combination of density-functional theory (DFT), molecular dynamics (MD) simulations with newly developed empirical potential parameters, and experimental measurements (AgTaO3 and CuTa2O6 only). Our results show that the MD-predicted friction force follows the trend AgTaO3 < CuTaO3 < CuTa2O6, which is consistent with the experimentally measured coefficients of friction. The wear performance from both MD and experiment exhibits the opposite trend, with CuTa2O6 providing the best resistance to wear. The sliding mechanisms are investigated using experimental characterization of the film composition after sliding, quantification of Ag or Cu cluster formation at the interface during the evolution of the film in MD, and DFT energy barriers for atom migration on the material surface. All our observations are consistent with the hypothesis that the formation of metal (or metal oxide) clusters on the surface are responsible for the friction and wear behavior of these materials.

An experimental means of transmitting pancreas disease in Atlantic salmon Salmo salar L. fry in freshwater.

A challenge model for pancreas disease in Atlantic salmon, Salmo salar L. fry, was developed comparing two salmonid alphavirus (SAV) subtypes: SAV1 and SAV5. Viral doses of 3 × 10(5) TCID50  mL(-1) for SAV1 and 3 × 10(4) for SAV5 were tested in triplicate tanks, each containing 450 salmon fry. Cumulative mortalities of 1.2% were recorded. Titres of virus recovered from the mortalities ranged from 10(2) to 10(7) TCID50  mL(-1) . Fry were sampled at 3, 5 and 7.5 weeks post-challenge. Sampling after 3 weeks revealed a high prevalence of infection in the absence of clinical signs, and infectious virus was recovered from 80% and 43% of sampled fry infected with SAV1 and SAV5, respectively. After 5 weeks pancreas, heart and red skeletal muscle lesions were generally observed, whilst degeneration in white skeletal muscle was observed only in fish infected with SAV1. In situ hybridisation confirmed the presence of viral genome in infected pancreas, heart and muscle. After 7.5 weeks, infectious virus (both isolates) was recovered from 13.3% of the fish sampled, with a viral titre of 10(2) TCID50  mL(-1) . Clearly, salmon fry are susceptible to SAV infection and pancreas disease.