bluuebunny/crossref_metadata_2025 huggingface dataset:
Japan NBI Expert Team classification: Narrow‐band imaging magnifying endoscopic classification of colorectal tumors
Authors: Sano Yasushi , Hirata Daizen , Saito Yutaka
Published: April 2018

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The Eating and Drinking Ability Classification System: concurrent validity and reliability in children with cerebral palsy
Authors: Tschirren Lea , Bauer Susanne , Hanser Chiara , Marsico Petra , Sellers Diane , van Hedel Hubertus J A
Published: April 2018

Aim

As there is little evidence for concurrent validity of the Eating and Drinking Ability Classification System (EDACS), this study aimed to determine its concurrent validity and reliability in children and adolescents with cerebral palsy (CP).

Method

After an extensive translation procedure, we applied the German language version to 52 participants with CP (30 males, 22 females, mean age 9y 7mo [SD 4y 2mo]). We correlated (Kendall's tau or Kτ) the EDACS levels with the Bogenhausener Dysphagiescore (BODS), and the EDACS level of assistance with the Manual Ability Classification System (MACS) and the item ‘eating’ of the Functional Independence Measure for Children (WeeFIM). We further quantified the interrater reliability between speech and language therapists (SaLTs) and between SaLTs and parents with Kappa (κ).

Results

The EDACS levels correlated highly with the BODS (Kτ=0.79), and the EDACS level of assistance correlated highly with the MACS (Kτ=0.73) and WeeFIM eating item (Kτ=−0.80). Interrater reliability proved almost perfect between SaLTs (EDACS: κ=0.94; EDACS level of assistance: κ=0.89) and SaLTs and parents (EDACS: κ=0.82; EDACS level of assistance: κ=0.89).

Interpretation

The EDACS levels and level of assistance seem valid and showed almost perfect interrater reliability when classifying eating and drinking problems in children and adolescents with CP.

What this paper adds

The Eating and Drinking Ability Classification System (EDACS) correlates well with a dysphagia score.

The EDACS level of assistance proves valid.

The German version of EDACS is highly reliable.

EDACS correlates moderately to highly with other classification systems.
Cover Image, Volume 20, Issue 5
Authors: Mietlicki‐Baase Elizabeth G. , Liberini Claudia G. , Workinger Jayme L. , Bonaccorso Ron L. , Borner Tito , Reiner David J. , Koch‐Laskowski Kieran , McGrath Lauren E. , Lhamo Rinzin , Stein Lauren M. , De Jonghe Bart C. , Holz George G. , Roth Christian L. , Doyle Robert P. , Hayes Matthew R.
Published: April 2018

The cover image, by Elizabeth G. Mietlicki‐Baase et al., is based on the Original Article A vitamin B12 conjugate of exendin‐4 improves glucose tolerance without associated nausea or hypophagia in rodents, DOI: 10.1111/dom.13222.

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Efficacy and safety of MYL‐1501D vs insulin glargine in patients with type 1 diabetes after 52 weeks: Results of the INSTRIDE 1 phase III study
Authors: Blevins Thomas C. , Barve Abhijit , Sun Bin , Ankersen Michael
Published: April 2018

Aim

To test the safety and efficacy of MYL‐1501D, a proposed insulin glargine biosimilar, in patients with type 1 diabetes mellitus (T1DM).

Methods

The safety and efficacy of MYL‐1501D and reference insulin glargine were evaluated in INSTRIDE 1, a 52‐week, open‐label, randomized, phase III study in patients with T1DM. The primary objective was to determine whether once‐daily MYL‐1501D was non‐inferior to once‐daily insulin glargine when administered in combination with mealtime insulin lispro based on change in glycated haemoglobin (HbA1c) from baseline to week 24. Secondary endpoints were changes in fasting plasma glucose, insulin dose, self‐monitored blood glucose and immunogenicity from baseline, and occurrences of hypoglycaemic, nocturnal hypoglycaemic and adverse events up to week 52.

Results

Overall, 558 patients were randomized 1:1 to MYL‐1501D or reference insulin glargine in combination with thrice‐daily mealtime insulin lispro for 52 weeks. The mean change in HbA1c from baseline to week 24 was 0.14% (standard error [SE] 0.054; 95% confidence interval [CI] 0.033, 0.244) for MYL‐1501D and 0.11% (SE 0.054; 95% CI 0.007, 0.220) for reference insulin glargine. MYL‐1501D had a safety profile similar to that of reference insulin glargine and was well tolerated in patients with T1DM up to week 52.

Conclusions

The upper 95% CI limit for mean change in HbA1c at week 24 indicated that MYL‐1501D was non‐inferior to reference insulin glargine. There were no clinically meaningful differences between groups in incidence of overall and nocturnal hypoglycaemia, local or systemic reactions, safety or immunogenicity.
Histological evaluation of the repair process of replanted rat teeth after storage in resveratrol dissolved in dimethyl sulphoxide
Authors: Poi Wilson R. , Sonoda Celso K. , Amaral Marina F. , Queiroz Alfredo F. , França Alline B. , Brandini Daniela A.
Published: April 2018

Background/Aim

The storage media is directly related to the prognosis of avulsed teeth, with resveratrol drawing attention due to its antioxidant and anti‐inflammatory proprieties. The aim of this study was to evaluate the repair process in rat teeth following delayed replantation after storage in resveratrol (R) dissolved in dimethyl sulphoxide (DMSO).

Materials and Methods

The upper right central incisors of 36 rats were divided into 4 groups. In group I, the teeth were extracted and immediately replanted. Group II teeth were stored in 50 mL R+DMSO (0.0512 g/mL), whereas group III teeth were stored in 50 mL pure DMSO, both for a period of 60 minutes. The teeth of group IV were stored dry for 60 minutes. The teeth of groups II, III and IV were then replanted, and the animals were euthanized after 60 days. Longitudinal histological cuts were HE stained for histomorphometric analysis of the periodontal ligament, alveolar bone, cementum and dentin.

Results

The analysis of HE stained histological sections showed the following statistical differences: the acute inflammatory process in the epithelial insertion was less prominent in group II than in group III; the organization of the periodontal ligament was better in group I, while the intensity and extension of acute inflammation in the periodontal ligament were better in group I, and worse in group III; the chronic inflammatory infiltrate was less in groups I and IV, and the depth and extent of resorption, as well as the repair of root resorption, were better in group I.

Conclusions

Storage in R+DMSO solution did not inhibit root resorption after delayed replantation in rat teeth. It is concluded that pure DMSO is not a suitable transport medium for avulsed teeth.
Soil organic carbon and nitrogen dynamics induced by continuous maize cropping compared to maize–soya bean rotation
Authors: Dou X. , Li F. , Cheng X. , Zhu P.
Published: April 2018

Agricultural measures that alter soil carbon (C) and nitrogen (N) dynamics might affect biogeochemical cycling. We combined soil chemical fractionation with isotope analyses to investigate C and N dynamics of soil organic matter pools (SOMP) after 25 years of cropping with the application of manure. Soil samples (0–20‐ and 20–40‐cm depths) were taken from the control (CK, i.e. the initial soil condition) and two cropping treatments: continuous maize (Zea mays L.) (MM) and maize–soya bean (Glycine max (L.) Merr.) rotation (MS). Samples were separated into recalcitrant and labile fractions and analysed for C and N content, δ13C and δ15N values, and soil C and N recalcitrance indices (RIC and RIN). Long‐term MM and MS cropping with manure application increased the soil organic carbon (SOC) storage considerably (1852.69 g C m−2 on average) because of enhanced recalcitrant C (RC) and labile C (LC). Soil organic nitrogen (SON) storage (166.79 g C m−2 on average) was also increased in MM and MS treatments from the accumulation of recalcitrant N (RN). In contrast, labile N (LN) was reduced in soil under MM and MS compared with CK. Storage of SOC was greater for MS than MM, but RIC was larger for MM than MS in the top layer, indicating that MM cropping might be more effective for future soil C sequestration because of the greater proportion of stable C stored. The RIN values were larger in cropped soil than in CK at 0–20‐cm depth. Moreover, the δ13C values indicated that the turnover rates of soil C were faster in MS than in MM. The more enriched δ15N values and decreased C:N ratios of SOMP occurred in soil under MM than under MS, indicating a greater loss of soil N with MM cropping.

Highlights

We investigated soil C and N dynamics under long‐term cropping combined with manure.

We combined soil chemical fractionation with isotope analyses to determine C sequestration and turnover.

Long‐term cropping increased recalcitrant C and N and labile C but decreased labile N.

Continuous maize cropping would be better for stable C accumulation than maize–soya bean rotation.
Physical properties controlling water repellency in synthesized granular solids
Authors: Saulick Y. , Lourenço S. D. N. , Baudet B. A. , Woche S. K. , Bachmann J.
Published: April 2018

The wettability of granular solids such as soil is known to depend primarily on two factors: their inherent chemistry and their physical properties, such as their particle size, particle shape and surface roughness. Nevertheless, the distinctive physical properties of such materials have not been fully explored to gauge their wettability. In this study, the difference in wettability between a flat solid (microscope slide) and three granular solids, namely glass beads (GB), Leighton Buzzard Sand (LBS) and crushed Glass (CG), which have different physical properties, were examined. The effect of chemistry was isolated by strongly hydrophobizing the above materials by treatment with dimethyldichlorosilane. Wettability measurements were made by measuring the water–solid contact angle (CA) by the sessile drop method after adhering one layer of uniformly oriented granular solids on to double‐sided adhesive tape initially attached to a microscope slide. Techniques for particle characterization included sieving for particle size, dynamic image analysis for particle shape and confocal laser microscopy to determine surface roughness. Results show that all CAs of the granular solids exceeded that of the hydrophobized microscope slide (103°). The crushed glass had the largest CA (125°). With all three granular solids, there was an increase in CAs as particle size decreased. In addition, as particles became more angular, CAs increased. The influence of shape on wettability became more predominant as particle size decreased. The surface roughness parameter, Ra, was investigated and shown to be sensitive to both the size and shape of the particles. A decrease in Ra from 95.4 to 34.1 μm increased CAs from 107 to 125°. A similar change in CA was shown to correspond to an increase in void fraction from 40.7 to 77.4%. Our results have practical implications for the optimum use of soil by enhancing or suppressing water repellency.

Highlights

How do the physical properties of granular solids such as soil influence their wettability?

Effects of physical properties of particles on CAs were investigated when isolated from effect of chemistry.

Particle shape becomes more important in gauging wettability as particle size decreases.

Wettability of granular solids may be physically controlled by specific particle characteristics.
Parasitic wasp‐associated symbiont affects plant‐mediated species interactions between herbivores
Authors: Cusumano Antonino , Zhu Feng , Volkoff Anne‐Nathalie , Verbaarschot Patrick , Bloem Janneke , Vogel Heiko , Dicke Marcel , Poelman Erik H.
Published: April 2018

Microbial mutualistic symbiosis is increasingly recognised as a hidden driving force in the ecology of plant–insect interactions. Although plant‐associated and herbivore‐associated symbionts clearly affect interactions between plants and herbivores, the effects of symbionts associated with higher trophic levels has been largely overlooked. At the third‐trophic level, parasitic wasps are a common group of insects that can inject symbiotic viruses (polydnaviruses) and venom into their herbivorous hosts to support parasitoid offspring development. Here, we show that such third‐trophic level symbionts act in combination with venom to affect plant‐mediated interactions by reducing colonisation of subsequent herbivore species. This ecological effect correlated with changes induced by polydnaviruses and venom in caterpillar salivary glands and in plant defence responses to herbivory. Because thousands of parasitoid species are associated with mutualistic symbiotic viruses in an intimate, specific relationship, our findings may represent a novel and widespread ecological phenomenon in plant–insect interactions.
Declining home range area predicts reduced late‐life survival in two wild ungulate populations
Authors: Froy Hannah , Börger Luca , Regan Charlotte E. , Morris Alison , Morris Sean , Pilkington Jill G. , Crawley Michael J. , Clutton‐Brock Tim H. , Pemberton Josephine M. , Nussey Daniel H.
Published: April 2018

Demographic senescence is increasingly recognised as an important force shaping the dynamics of wild vertebrate populations. However, our understanding of the processes that underpin these declines in survival and fertility in old age remains limited. Evidence for age‐related changes in foraging behaviour and habitat use is emerging from wild vertebrate studies, but the extent to which these are driven by within‐individual changes, and the consequences for fitness, remain unclear. Using longitudinal census observations collected over four decades from two long‐term individual‐based studies of unmanaged ungulates, we demonstrate consistent within‐individual declines in home range area with age in adult females. In both systems, we found that within‐individual decreases in home range area were associated with increased risk of mortality the following year. Our results provide the first evidence from the wild that age‐related changes in space use are predictive of adult mortality.
What Happens when Companies (don’t) Do What they Said they would? Stock Market Reactions to Strategic Integrity
Authors: Mavis Christos P. , Richter Ansgar , Landau Christian , Schmidt Sascha L. , Simons Tony , Steinbock Kai
Published: April 2018

Literature on the ‘power of words’ has emphasized the importance of a firm's corporate communication as a source of legitimacy and reputation in the eyes of its stakeholders. We argue that it is not just the content or style of a firm's communication about its strategy, but also the alignment between this communication and its subsequent strategic actions that help build legitimacy among stakeholders and creating firm performance. We introduce the organization‐level construct of ‘strategic integrity’ to capture the notion of alignment between a firm's strategy communication and its subsequent strategic actions. We investigate the importance of strategic integrity using the case of the German pharmaceuticals firm Bayer AG in the context of its portfolio restructuring. The results of an event study of 80 acquisitions/divestments indicate that stock markets react positively to strategic integrity.
Geographic isolation and larval dispersal shape seascape genetic patterns differently according to spatial scale
Authors: Dalongeville Alicia , Andrello Marco , Mouillot David , Lobreaux Stéphane , Fortin Marie‐Josée , Lasram Frida , Belmaker Jonathan , Rocklin Delphine , Manel Stéphanie
Published: April 2018

Genetic variation, as a basis of evolutionary change, allows species to adapt and persist in different climates and environments. Yet, a comprehensive assessment of the drivers of genetic variation at different spatial scales is still missing in marine ecosystems. Here, we investigated the influence of environment, geographic isolation, and larval dispersal on the variation in allele frequencies, using an extensive spatial sampling (47 locations) of the striped red mullet (Mullus surmuletus) in the Mediterranean Sea. Univariate multiple regressions were used to test the influence of environment (salinity and temperature), geographic isolation, and larval dispersal on single nucleotide polymorphism (SNP) allele frequencies. We used Moran's eigenvector maps (db‐MEMs) and asymmetric eigenvector maps (AEMs) to decompose geographic and dispersal distances in predictors representing different spatial scales. We found that salinity and temperature had only a weak effect on the variation in allele frequencies. Our results revealed the predominance of geographic isolation to explain variation in allele frequencies at large spatial scale (>1,000 km), while larval dispersal was the major predictor at smaller spatial scale (<1,000 km). Our findings stress the importance of including spatial scales to understand the drivers of spatial genetic variation. We suggest that larval dispersal allows to maintain gene flows at small to intermediate scale, while at broad scale, genetic variation may be mostly shaped by adult mobility, demographic history, or multigenerational stepping‐stone dispersal. These findings bring out important spatial scale considerations to account for in the design of a protected area network that would efficiently enhance protection and persistence capacity of marine species.
Prepubic tendon rupture in the mare
Authors: Jalim S. L.
Published: April 2018

The following article discusses the clinical appearance, diagnosis, management and prognosis of abdominal wall tearing and prepubic tendon (PPT) ruptures of mares.
A Guide to IL‐1 family cytokines in adjuvanticity
Authors: Muñoz‐Wolf Natalia , Lavelle Ed C.
Published: April 2018

Growing awareness of the multiplicity of roles for the IL‐1 family in immune regulation has prompted research exploring these cytokines in the context of vaccine‐induced immunity. While tightly regulated, cytokines of the IL‐1 family are normally released in response to cellular stress and in combination with other danger‐/damage‐associated molecular patterns (DAMPs), triggering potent local and systemic immune responses. In the context of infection or autoimmunity, engagement of IL‐1 family receptors links robust innate responses to adaptive immunity. Clinical and experimental evidence has revealed that many vaccine adjuvants induce the release of one or multiple IL‐1 family cytokines. The coordinated release of IL‐1 family members in response to adjuvant‐induced damage or cell death may be a determining factor in the transition from local inflammation to the induction of an adaptive response. Here, we analyse the effects of IL‐1 family cytokines on innate and adaptive immunity with a particular emphasis on activation of antigen‐presenting cells and induction of T cell‐mediated immunity, and we address in detail the contribution of these cytokines to the modes of action of vaccine adjuvants including those currently approved for human use.
Immune imbalance of global gene expression, and cytokine, chemokine and selectin levels in the brains of offspring with social deficits via maternal immune activation
Authors: Hsueh P.‐T. , Lin H.‐H. , Wang H.‐H. , Liu C.‐L. , Ni W.‐F. , Liu J.‐K. , Chang H.‐H. , Sun D.‐S. , Chen Y.‐S. , Chen Y.‐L.
Published: April 2018

The murine maternal immune activation (MIA) offspring model enables longitudinal studies to explore aberrant social behaviors similar to those observed in humans. High levels of cytokines, chemokines and cell adhesion molecules (CAM) have been found in the plasma and/or brains of psychiatric patients. We hypothesized that upregulation of the systemic or brain immune response has an augmenting effect by potentially increasing the interplay between the neuronal and immune systems during the growth of the MIA offspring. In this study, a C57BL/6j MIA female offspring model exhibiting social deficits was established. The expression of fetal interferon (IFN)‐stimulated (gbp3, irgm1, ifi44), adolescent immunodevelopmental transcription factor (eg, r2, tfap2b), hormone (pomc, hcrt), adult selectin (sell, selp) and neuroligin (nlgn2) genes was altered. Systemic upregulation of endogenous IL‐10 occurred at the adult stage, while both IL‐1β and IL‐6 were increased and persisted in the sera throughout the growth of the MIA offspring. The cerebral IL‐6 levels were endogenously upregulated, but both MCP‐1 (macrophage inflammatory protein‐1) and L‐selectin levels were downregulated at the adolescent and/or adult stages. However, the MIA offspring were susceptible to lipopolysaccharide (LPS) stimulation. After reinjecting the MIA offspring with LPS in adulthood, a variety of sera and cerebral cytokines, chemokines and CAMs were increased. Particularly, both MCP‐1 and L‐selectin showed relatively high expression in the brain compared with the expression levels in phosphate‐buffered saline (PBS)‐treated offspring injected with LPS. Potentially, MCP‐1 was attracted to the L‐selectin‐mediated immune cells due to augmentation of the immune response following stimulation in MIA female offspring.
Microbial diversity and biomarker analysis of modern freshwater microbialites from Laguna Bacalar, Mexico
Authors: Johnson D. B. , Beddows P. A. , Flynn T. M. , Osburn M. R.
Published: April 2018

Laguna Bacalar is a sulfate‐rich freshwater lake on the Yucatan Peninsula that hosts large microbialites. High sulfate concentrations distinguish Laguna Bacalar from other freshwater microbialite sites such as Pavilion Lake and Alchichica, Mexico, as well as from other aqueous features on the Yucatan Peninsula. While cyanobacterial populations have been described here previously, this study offers a more complete characterization of the microbial populations and corresponding biogeochemical cycling using a three‐pronged geobiological approach of microscopy, high‐throughput DNA sequencing, and lipid biomarker analyses. We identify and compare diverse microbial communities of Alphaproteobacteria, Deltaproteobacteria, and Gammaproteobacteria that vary with location along a bank‐to‐bank transect across the lake, within microbialites, and within a neighboring mangrove root agglomeration. In particular, sulfate‐reducing bacteria are extremely common and diverse, constituting 7%–19% of phylogenetic diversity within the microbialites, and are hypothesized to significantly influence carbonate precipitation. In contrast, Cyanobacteria account for less than 1% of phylogenetic diversity. The distribution of lipid biomarkers reflects these changes in microbial ecology, providing meaningful biosignatures for the microbes in this system. Polysaturated short‐chain fatty acids characteristic of cyanobacteria account for <3% of total abundance in Laguna Bacalar microbialites. By contrast, even short‐chain and monounsaturated short‐chain fatty acids attributable to both Cyanobacteria and many other organisms including types of Alphaproteobacteria and Gammaproteobacteria constitute 43%–69% and 17%–25%, respectively, of total abundance in microbialites. While cyanobacteria are the largest and most visible microbes within these microbialites and dominate the mangrove root agglomeration, it is clear that their smaller, metabolically diverse associates are responsible for significant biogeochemical cycling in this microbialite system.
Interdisciplinary knowledge exchange across scales in a globally changing marine environment
Authors: McDonald Karlie S. , Hobday Alistair J. , Fulton Elizabeth A. , Thompson Peter A.
Published: April 2018

The effects of anthropogenic global environmental change on biotic and abiotic processes have been reported in aquatic systems across the world. Complex synergies between concurrent environmental stressors and the resilience of the system to regime shifts, which vary in space and time, determine the capacity for marine systems to maintain structure and function with global environmental change. Consequently, an interdisciplinary approach that facilitates the development of new methods for the exchange of knowledge between scientists across multiple scales is required to effectively understand, quantify and predict climate impacts on marine ecosystem services. We use a literature review to assess the limitations and assumptions of current pathways to exchange interdisciplinary knowledge and the transferability of research findings across spatial and temporal scales and levels of biological organization to advance scientific understanding of global environmental change in marine systems. We found that species‐specific regional scale climate change research is most commonly published, and “supporting” is the ecosystem service most commonly referred to in publications. In addition, our paper outlines a trajectory for the future development of integrated climate change science for sustaining marine ecosystem services such as investment in interdisciplinary education and connectivity between disciplines.
An empirical test of the relative and combined effects of land‐cover and climate change on local colonization and extinction
Authors: Yalcin Semra , Leroux Shawn James
Published: April 2018

Land‐cover and climate change are two main drivers of changes in species ranges. Yet, the majority of studies investigating the impacts of global change on biodiversity focus on one global change driver and usually use simulations to project biodiversity responses to future conditions. We conduct an empirical test of the relative and combined effects of land‐cover and climate change on species occurrence changes. Specifically, we examine whether observed local colonization and extinctions of North American birds between 1981–1985 and 2001–2005 are correlated with land‐cover and climate change and whether bird life history and ecological traits explain interspecific variation in observed occurrence changes. We fit logistic regression models to test the impact of physical land‐cover change, changes in net primary productivity, winter precipitation, mean summer temperature, and mean winter temperature on the probability of Ontario breeding bird local colonization and extinction. Models with climate change, land‐cover change, and the combination of these two drivers were the top ranked models of local colonization for 30%, 27%, and 29% of species, respectively. Conversely, models with climate change, land‐cover change, and the combination of these two drivers were the top ranked models of local extinction for 61%, 7%, and 9% of species, respectively. The quantitative impacts of land‐cover and climate change variables also vary among bird species. We then fit linear regression models to test whether the variation in regional colonization and extinction rate could be explained by mean body mass, migratory strategy, and habitat preference of birds. Overall, species traits were weakly correlated with heterogeneity in species occurrence changes. We provide empirical evidence showing that land‐cover change, climate change, and the combination of multiple global change drivers can differentially explain observed species local colonization and extinction.
Counterintuitive effects of global warming‐induced wind patterns on primary production in the Northern Humboldt Current System
Authors: Mogollón Rodrigo , R. Calil Paulo H.
Published: April 2018

It has been hypothesized that global warming will strengthen upwelling‐favorable winds in the Northern Humboldt Current System (NHCS) as a consequence of the increase of the land–sea thermal gradient along the Peruvian coast. The effect of strengthened winds in this region is assessed with the use of a coupled physical–biogeochemical model forced with projected and climatological winds. Strengthened winds induce an increase in primary production of 2% per latitudinal degree from 9.5°S to 5°S. In some important coastal upwelling sites primary production is reduced. This is due to a complex balance between nutrient availability, nutrient use efficiency, as well as eddy‐ and wind‐driven factors. Mesoscale activity induces a net offshore transport of inorganic nutrients, thus reducing primary production in the coastal upwelling region. Wind mixing, in general disadvantageous for primary producers, leads to shorter residence times in the southern and central coastal zones. Overall, instead of a proportional enhancement in primary production due to increased winds, the NHCS becomes only 5% more productive (+5 mol C m−2 year−1), 10% less limited by nutrients and 15% less efficient due to eddy‐driven effects. It is found that regions with a initial strong nutrient limitation are more efficient in terms of nutrient assimilation which makes them more resilient in face of the acceleration of the upwelling circulation.
Plant organic acids in fresh and ensiled forage plants
Authors: Udén P.
Published: April 2018

Timothy, red clover and white clover from two cuts and two stages of maturity and whole crops (WC) of barley, wheat and maize from three stages of maturity were analysed for individual plant organic acids (OAs) before and after ensiling in mini‐silos. Total OA levels, as previously reported, were generally lower in WC (14–70 g/kg dry matter) in comparison with leys (51–98 g/kg dry matter). Succinic, shikimic and fumaric acid levels were very low in all samples, while quinic, malonic, malic and citric acid constituted >90% of total OAs in all samples except maize. Maize had lower total OA levels than any other species but was the only one containing detectable levels of oxalic and aconitic acid. The sum of oxalic and aconitic acid decreased, however, from 89% to 35% of total OAs from early to late maturity, while there was a parallel increase in citric acid with increasing harvest date. Total OA level was unaffected in the ley crops by maturity, cut and species (p > .1), but among WC, wheat was higher than maize (p < .05) and also higher at early, than late maturity (p < .01). Silage total OA levels were lower than in parent crops (p < .001). Individual OA levels decreased by 38%–56% from ensiling, except for oxalic acid, which was unaffected, and succinic acid, which increased >7‐fold. Excluding succinic acid, which is also a fermentation product, average loss during ensiling was 44%.
Improved Method for Estimating Reaction Rates During Push‐Pull Tests
Authors: Paradis Charles J. , Dixon Emma R. , Lui Lauren M. , Arkin Adam P. , Parker Jack C. , Istok Jonathan D. , Perfect Edmund , McKay Larry D. , Hazen Terry C.
Published: April 2018

The breakthrough curve obtained from a single‐well push‐pull test can be adjusted to account for dilution of the injection fluid in the aquifer fluid. The dilution‐adjusted breakthrough curve can be analyzed to estimate the reaction rate of a solute. The conventional dilution‐adjusted method assumes that the ratios of the concentrations of the nonreactive and reactive solutes in the injection fluid vs. the aquifer fluid are equal. If this assumption is invalid, the conventional method will generate inaccurate breakthrough curves and may lead to erroneous conclusions regarding the reactivity of a solute. In this study, a new method that generates a dilution‐adjusted breakthrough curve was theoretically developed to account for any possible combination of nonreactive and reactive solute concentrations in the injection and aquifer fluids. The newly developed method was applied to a field‐based data set and was shown to generate more accurate dilution‐adjusted breakthrough curves. The improved dilution‐adjusted method presented here is simple, makes no assumptions regarding the concentrations of the nonreactive and reactive solutes in the injection and aquifer fluids, and easily allows for estimating reaction rates during push‐pull tests.
Investigating Impacts of Climate Change on Irrigation Water Demands and Its Resulting Consequences on Groundwater Using CMIP5 Models
Authors: Goodarzi Mustafa , Abedi‐Koupai Jahangir , Heidarpour Manouchehr
Published: April 2018

In this study, the impacts of climate change on crop water requirements and irrigation water requirements on the regional cropping pattern were evaluated using two climate change scenarios and combinations of 20 GCM models. Different models including CROPWAT, MODFLOW, and statistical models were used to evaluate the climate change impacts. The results showed that in the future period (2017 to 2046) the temperature in all months of the year will increase at all stations. The average annual precipitation decline in Isfahan, Tiran, Flavarjan, and Lenj stations for RCP 4.5 and RCP 8.5 scenarios are 18.6 and 27.6%, 15.2 and 18%, 22.5 and 31.5%, and 10.5 and 12.1%, respectively. The average increase in the evapotranspiration for RCP 4.5 and RCP 8.5 scenarios are about 2.5 and 4.1%, respectively. The irrigation water demands increases considerably and for some crops, on average 18%. Among the existing crops in the cropping pattern, barley, cumin, onion, wheat, and forage crops are more sensitive and their water demand will increase significantly. Results indicate that climate change could have a significant impact on water resources consumption. By considering irrigation efficiency in the region, climate change impacts will result in about 35 to 50 million m3/year, over‐extraction from the aquifer. This additional exploitation causes an extra drop of 0.4 to 0.8 m in groundwater table per year in the aquifer. Therefore, with regard to the critical condition of the aquifer, management and preventive measures to deal with climate change in the future is absolutely necessary.
Recurrent F8 and F9 gene variants result from a founder effect in two large French haemophilia cohorts
Authors: Lassalle F. , Marmontel O. , Zawadzki C. , Fretigny M. , Bouvagnet P. , Vinciguerra C.
Published: April 2018

Introduction

Haemophilia A (HA) and haemophilia B (HB) are X‐linked recessive diseases, caused by a large number of pathogenic variants in the F8 and F9 genes. With the exception of introns 22 and 1 inversions which are frequent in severe HA cases, about 2000 unique variants in F8 and 1000 in F9 have been described in databases and their recurrence remains limited.

Aim and methods

During routine analysis, we identified two recurrent missense variants, the F8 gene c.1244C>T, p.Ala415Val variant in 27 HA patients and the F9 gene c.835G>A, p.Ala279Thr variant in 34 HB patients, in two groups of haemophiliac patients from two different regions of France. We aimed to identify whether these variants result from a founder effect. We performed haplotype reconstruction after analysis of extragenic and intragenic polymorphic markers. The ESTIAGE programme was used to estimate the age of the variant.

Results

We identified a common ancestral haplotype HA1, in all the HA patients sharing the p.Ala415Val variant, and HB1 for 22 of 34 HB patients sharing the p.Ala279Thr variant. The estimated time of occurrence of the founder variant was between the 13th and 17th century (95% CI: 16 to 29 generations) for the F8 variant and between the 3rd and the 11th century for the F9 variant (95% CI: 44 to 72 generations).

Conclusion

This study supports a founder effect for these two variants in the two largest reported cohorts of haemophilia patients with an identical variant. These pathogenic variants are among the three most early reported variants in haemophilia.
Development of a risk‐prediction model for Middle East respiratory syndrome coronavirus infection in dialysis patients
Authors: Ahmed Anwar E. , Alshukairi Abeer N. , Al‐Jahdali Hamdan , Alaqeel Mody , Siddiq Salma S. , Alsaab Hanan A. , Sakr Ezzeldin A. , Alyahya Hamed A. , Alandonisi Munzir M. , Subedar Alaa T. , Aloudah Nouf M. , Baharoon Salim , Alsalamah Majid A. , Al Johani Sameera , Alghamdi Mohammed G.
Published: April 2018

Introduction The Middle East respiratory syndrome coronavirus (MERS‐CoV) infection can cause transmission clusters and high mortality in hemodialysis facilities. We attempted to develop a risk‐prediction model to assess the early risk of MERS‐CoV infection in dialysis patients.

Methods This two‐center retrospective cohort study included 104 dialysis patients who were suspected of MERS‐CoV infection and diagnosed with rRT‐PCR between September 2012 and June 2016 at King Fahd General Hospital in Jeddah and King Abdulaziz Medical City in Riyadh. We retrieved data on demographic, clinical, and radiological findings, and laboratory indices of each patient.

Findings A risk‐prediction model to assess early risk for MERS‐CoV in dialysis patients has been developed. Independent predictors of MERS‐CoV infection were identified, including chest pain (OR = 24.194; P = 0.011), leukopenia (OR = 6.080; P = 0.049), and elevated aspartate aminotransferase (AST) (OR = 11.179; P = 0.013). The adequacy of this prediction model was good (P = 0.728), with a high predictive utility (area under curve [AUC] = 76.99%; 95% CI: 67.05% to 86.38%). The prediction of the model had optimism‐corrected bootstrap resampling AUC of 71.79%. The Youden index yielded a value of 0.439 or greater as the best cut‐off for high risk of MERS infection.

Discussion This risk‐prediction model in dialysis patients appears to depend markedly on chest pain, leukopenia, and elevated AST. The model accurately predicts the high risk of MERS‐CoV infection in dialysis patients. This could be clinically useful in applying timely intervention and control measures to prevent clusters of infections in dialysis facilities or other health care settings. The predictive utility of the model warrants further validation in external samples and prospective studies.
Long‐term efficacy and safety of sucroferric oxyhydroxide in African American dialysis patients
Authors: Sprague Stuart M. , Ketteler Markus , Covic Adrian C. , Floege Jürgen , Rakov Viatcheslav , Walpen Sebastian , Rastogi Anjay
Published: April 2018

Introduction: Sucroferric oxyhydroxide (SFOH) is a non‐calcium, iron‐based phosphate binder that demonstrated sustained serum phosphorus (sP) control, good tolerability, and lower pill burden, vs. sevelamer carbonate (“sevelamer”), in a Phase 3 study conducted in dialysis patients with hyperphosphatemia. This analysis evaluates the efficacy and safety of SFOH and sevelamer among African American (AA) patients participating in the trial.

Methods: Post hoc analysis of a 24‐week, Phase 3, open‐label trial (NCT01324128) and its 28‐week extension study (NCT01464190). Patients were randomized 2:1 to SFOH (1.0–3.0 g/day) or sevelamer (2.4−14.4 g/day) for up to 52 weeks.

Findings: Of 549 patients who completed the Phase 3 study and extension, 100 (18.2%) AA patients were eligible for efficacy analysis (SFOH, n = 48; sevelamer, n = 52). sP concentrations decreased rapidly and comparably with both treatments by Week 8 (mean ± standard deviation change from baseline: −1.9 ± 1.9 mg/dL for SFOH and −2.2 ± 1.8 mg/dL for sevelamer). These reductions were maintained for 52 weeks (−2.1 ± 2.6 and −2.1 ± 1.6 mg/dL) and achieved with a lower mean pill burden (3.4 ± 1.4 vs. 7.6 ± 2.9 tablets/day) with SFOH vs. sevelamer. Treatment adherence rates (adherence within 70%–120% of expected medication intake) were 79.2% with SFOH and 59.6% with sevelamer. The proportion of patients reporting serious adverse events (AEs) was 27.7% with SFOH and 30.7% with sevelamer. More patients withdrew due to treatment‐emergent AEs with SFOH vs. sevelamer (18.5% vs. 8.0%). The most common AEs with both treatments were gastrointestinal‐related: diarrhea and discolored feces with SFOH, and nausea, vomiting, and constipation with sevelamer.

Discussion: SFOH is an efficacious and well‐tolerated treatment for hyperphosphatemia in AA dialysis patients, with a lower pill burden and an improved adherence rate vs. sevelamer. These findings were consistent with the wider US patient population and the overall study population.
Helicobacter pylori infection‐induced H3Ser10 phosphorylation in stepwise gastric carcinogenesis and its clinical implications
Authors: Yang Tao‐Tao , Cao Na , Zhang Hai‐Hui , Wei Jian‐Bo , Song Xiao‐Xia , Yi Dong‐Min , Chao Shuai‐Heng , Zhang Li‐Da , Kong Ling‐Fei , Han Shuang‐Yin , Yang Yu‐Xiu , Ding Song‐Ze
Published: April 2018

Background

Our previous works have demonstrated that Helicobacter pylori (Hp) infection can alter histone H3 serine 10 phosphorylation status in gastric epithelial cells. However, whether Helicobacter pylori‐induced histone H3 serine 10 phosphorylation participates in gastric carcinogenesis is unknown. We investigate the expression of histone H3 serine 10 phosphorylation in various stages of gastric disease and explore its clinical implication.

Materials and Methods

Stomach biopsy samples from 129 patients were collected and stained with histone H3 serine 10 phosphorylation, Ki67, and Helicobacter pylori by immunohistochemistry staining, expressed as labeling index. They were categorized into nonatrophic gastritis, chronic atrophic gastritis, intestinal metaplasia, low‐grade intraepithelial neoplasia, high‐grade intraepithelial neoplasia, and intestinal‐type gastric cancer groups. Helicobacter pylori infection was determined by either 13C‐urea breath test or immunohistochemistry staining.

Results

In Helicobacter pylori‐negative patients, labeling index of histone H3 serine 10 phosphorylation was gradually increased in nonatrophic gastritis, chronic atrophic gastritis, intestinal metaplasia groups, peaked at low‐grade intraepithelial neoplasia, and declined in high‐grade intraepithelial neoplasia and gastric cancer groups. In Helicobacter pylori‐infected patients, labeling index of histone H3 serine 10 phosphorylation followed the similar pattern as above, with increased expression over the corresponding Helicobacter pylori‐negative controls except in nonatrophic gastritis patient whose labeling index was decreased when compared with Helicobacter pylori‐negative control. Labeling index of Ki67 in Helicobacter pylori‐negative groups was higher in gastric cancer than chronic atrophic gastritis and low‐grade intraepithelial neoplasia groups, and higher in intestinal metaplasia group compared with chronic atrophic gastritis group. In Helicobacter pylori‐positive groups, Ki67 labeling index was increased stepwise from nonatrophic gastritis to gastric cancer except slightly decrease in chronic atrophic gastritis group. In addition, we noted that histone H3 serine 10 phosphorylation staining is accompanied with its location changes from gastric gland bottom expanded to whole gland as disease stage progress.

Conclusions

These results indicate that stepwise gastric carcinogenesis is associated with altered histone H3 serine 10 phosphorylation, Helicobacter pylori infection enhances histone H3 serine 10 phosphorylation expression in these processes; it is also accompanied with histone H3 serine 10 phosphorylation location change from gland bottom staining expand to whole gland expression. The results suggest that epigenetic dysregulation may play important roles in Helicobacter pylori‐induced gastric cancer.
Neuropathic pain: A patient‐centred approach to measuring outcomes
Authors: Hwang Steve , van Nooten Floortje , Wells Ted , Ryan Aisling , Crawford Bruce , Evans Christopher , English Marci
Published: April 2018

Background

Neuropathic pain (NP) is a complex, chronic pain state initiated by a primary lesion or dysfunction of the nervous system and presents as a variety of symptoms across multiple disease states.

Objective

To develop a patient‐centred conceptual model of symptoms and impacts in subjects with diabetic peripheral neuropathy (DPN) or post‐herpetic neuralgia (PHN) that can inform the measurement strategy in clinical trials.

Method

Thirty subjects with DPN or PHN participated in in‐person interviews which were performed until saturation was achieved. Transcripts were analysed in ATLAS.ti.

Results

Interviews were completed with DPN subjects (United States, n = 10; Japan, n = 10) and PHN subjects (United States, n = 5; Japan, n = 5). Numbness and tingling were frequently reported symptoms in the DPN population while itchiness and hypersensitivity were predominant in PHN. Both populations experienced burning and ache/soreness with similar frequency. DPN subjects experienced pain primarily in their lower extremity (eg feet, ankles), while PHN subjects experienced pain primarily in the chest and back. Impacts reported by DPN subjects included difficulty walking, sleep disturbance and climbing stairs. Impacts in PHN subjects included sleep disturbance, avoidance of physical contact, being angry/frustrated and being sad/depressed. Overall, concepts in Japan were not qualitatively different from the United States. Conceptual models of NP were generated based on the concepts elicited.

Conclusions

This research highlights core concepts to measure from the patient's perspective. Moreover, it enables the assessment of existing measures, the possible modification of these measures, or if a new NP measure with improved sensitivity and responsiveness is merited.
The use of funnel plots with regression as a tool to visually compare HIV treatment outcomes between centres adjusting for patient characteristics and size: a UK Collaborative HIV Cohort study
Authors: Gompels M , Michael S , Jose S , Hill T , Trevelion R , Sabin CA , May MT
Published: April 2018

Objectives

A measure used for assessing the effectiveness of HIV care and comparing clinical centres is the proportion of people starting antiretroviral therapy (ART) with viral suppression (VS) after 1 year. We propose a method that adjusts for patients’ demographic characteristics, and visually compares this measure between different sites accounting for centre size.

Methods

We analysed viral load measurements for UK Collaborative HIV Cohort (UK CHIC) patients starting ART between 2006 and 2013. We used logistic regression to estimate the proportion with VS after 1 year of ART adjusted for patient mix (in terms of age and a combined gender/ethnicity/acquisition mode variable) and calendar year. We compared outcomes between centres using funnel plots which account for centre size.

Results

The overall proportion of the cohort with VS 1 year after starting ART was 90% and increased from 83% to 93% between 2006 and 2013. VS was lower in younger individuals. White men who have sex with men (MSM) had the highest (94%), and black African (81%) and white (82%) heterosexual women the lowest proportions achieving VS. Comparing the unadjusted funnel plot with the adjusted, there were movements of some centres from outside to inside the 95% contour limits, which was largely explained by the patient mix of these centres.

Conclusions

VS 1 year after ART start was associated with demographic characteristics and centre size; therefore, to compare the performances of centres, adjustment for these factors is required. Adjusted funnel plot is an effective tool which accounts for both the demographic characteristics and the centre size. Social factors, rather than treatment decisions within the control of the centres, may drive differences in outcomes.