bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patients with the worst outcomes after paracetamol (acetaminophen)‐induced liver failure have an early monocytopenia
Authors: Moore J. K. , MacKinnon A. C. , Man T. Y. , Manning J. R. , Forbes S. J. , Simpson K. J. 
Published: November 2016

SummaryBackgroundAcute liver failure (ALF) is associated with significant morbidity and mortality. Studies have implicated the immune response, especially monocyte/macrophages as being important in dictating outcome.AimTo investigate changes in the circulating monocytes and other immune cells serially in patients with ALF, relate these with cytokine concentrations, monocyte gene expression and patient outcome.MethodsIn a prospective case–control study in the Scottish Liver Transplant Unit, Royal Infirmary Edinburgh, 35 consecutive patients admitted with paracetamol‐induced liver failure (POD‐ALF), 10 patients with non‐paracetamol causes of ALF and 16 controls were recruited. The peripheral blood monocyte phenotype was analysed by flow cytometry, circulating cytokines quantified by protein array and monocyte gene expression array performed and related to outcome.ResultsOn admission, patients with worst outcomes after POD‐ALF had a significant monocytopenia, characterised by reduced classical and expanded intermediate monocyte population. This was associated with reduced circulating lymphocytes and natural killer cells, peripheral cytokine patterns suggestive of a ‘cytokine storm’ and increased concentrations of cytokines associated with monocyte egress from the bone marrow. Gene expression array did not differentiate patient outcome. At day 4, there was no significant difference in monocyte, lymphocyte or natural killer cells between survivors and the patients with adverse outcomes.ConclusionsSevere paracetamol liver failure is associated with profound changes in the peripheral blood compartment, particularly in monocytes, related with worse outcomes. This is not seen in patients with non‐paracetamol‐induced liver failure. Significant monocytopenia on admission may allow earlier clarification of prognosis, and it highlights a potential target for therapeutic intervention.
Recent advances in T‐cell immunotherapy for haematological malignancies
Authors: Rouce Rayne H. , Sharma Sandhya , Huynh Mai , Heslop Helen E. 
Published: November 2016

SummaryIn vitro discoveries have paved the way for bench‐to‐bedside translation in adoptive T cell immunotherapy, resulting in remarkable clinical responses in a variety of haematological malignancies. Adoptively transferred T cells genetically modified to express CD19 CARs have shown great promise, although many unanswered questions regarding how to optimize T‐cell therapies for both safety and efficacy remain. Similarly, T cells that recognize viral or tumour antigens though their native receptors have produced encouraging clinical responses. Honing manufacturing processes will increase the availability of T‐cell products, while combining T‐cell therapies has the ability to increase complete response rates. Lastly, innovative mechanisms to control these therapies may improve safety profiles while genome editing offers the prospect of modulating T‐cell function. This review will focus on recent advances in T‐cell immunotherapy, highlighting both clinical and pre‐clinical advances, as well as exploring what the future holds.
Heterogeneous patterns of abundance of epigeic arthropod taxa along a major elevation gradient
Authors: Röder Juliane , Detsch Florian , Otte Insa , Appelhans Tim , Nauss Thomas , Peters Marcell K. , Brandl Roland 
Published: November 2016

AbstractSpecies diversity is the variable most commonly studied in recent ecological research. Ecological processes, however, are driven by individuals and affected by their abundances. Understanding the variation in animal abundances along climatic gradients is important for predicting changes in ecosystem processes under global warming. High abundances make arthropods, despite their small body sizes, important actors in food webs, yet abundance distributions of major arthropod taxa along climatic gradients remain poorly documented. We sampled arthropod assemblages in disturbed and undisturbed vegetation types along an elevational gradient of 860–4550 m asl on the southern slopes of Mt. Kilimanjaro, Tanzania. In our analysis, we focused on 13 taxa of arthropods that represented three major functional groups: predators, herbivores, and decomposers. Abundance patterns were unimodal for most of the taxa and functional groups, including decomposer arthropods, and most of them peaked at low elevations in lower montane forest. When we assigned beetles to functional groups, however, decomposer beetle abundances declined almost linearly, and abundances of predator beetles (ca. 2400 m asl) and herbivore beetles (ca. 3000 m asl, undisturbed vegetation) peaked at higher elevations and exhibited unimodal patterns. Temperature, not primary productivity, was the best predictor of abundance for most of the taxa and groups. Disturbance was only of minor importance. Our results revealed different trends in the response of arthropod abundance along the elevational gradient that depended on the level of taxonomic and functional resolution. This highlights the need for more comparisons of different taxa along the same climatic gradients.
(Z)‐2‐(3‐Chlorobenzylidene)‐3,4‐dihydro‐N‐(2‐methoxyethyl)‐3‐oxo‐2H‐benzo[b][1,4]oxazine‐6‐carboxamide as GSK‐3β inhibitor: Identification by virtual screening and its validation in enzyme‐ and cell‐based assay
Authors: Joshi Prashant , Gupta Mehak , Vishwakarma Ram A. , Kumar Ajay , Bharate Sandip B. 
Published: November 2016

Glycogen synthase kinase 3β (GSK‐3β) is a widely investigated molecular target for numerous diseases including Alzheimer's disease, cancer, and diabetes mellitus. The present study was aimed to discover new scaffolds for GSK‐3β inhibition, through protein structure‐guided virtual screening approach. With the availability of large number of GSK‐3β crystal structures with varying degree of RMSD in protein backbone and RMSF in side chain geometry, herein appropriate crystal structures were selected based on the characteristic ROC curve and percentage enrichment of actives. The validated docking protocol was employed to screen a library of 50,000 small molecules using molecular docking and binding affinity calculations. Based on the GLIDE docking score, Prime MMGB/SA binding affinity, and interaction pattern analysis, the top 50 ligands were selected for GSK‐3β inhibition. (Z)‐2‐(3‐chlorobenzylidene)‐3,4‐dihydro‐N‐(2‐methoxyethyl)‐3‐oxo‐2H‐benzo[b][1,4]oxazine‐6‐carboxamide (F389‐0663, 7) was identified as a potent inhibitor of GSK‐3β with an IC50 value of 1.6 μm. Further, GSK‐3β inhibition activity was then investigated in cell‐based assay. The treatment of neuroblastoma N2a cells with 12.5 μm of F389‐0663 resulted in the significant increase in GSK‐3β Ser9 levels, which is indicative of the GSK‐3β inhibitory activity of a compound. The molecular dynamic simulations were carried out to understand the interactions of F389‐0663 with GSK‐3β protein.
Design, synthesis and in vitro antiplasmodial activity of some bisquinolines against chloroquine‐resistant strain
Authors: Kondaparla Srinivasarao , Agarwal Pooja , Srivastava Kumkum , Puri Sunil K. , Katti Seturam B. 
Published: November 2016

A series of novel bisquinoline compounds comprising N1‐(7‐chloroquinolin‐4‐yl) ethane‐1,2‐diamine and 7‐chloro‐N‐(2‐(piperazin‐1‐yl)ethyl)quinolin‐4‐amine connected with 7‐chloro‐4‐aminoquinoline containing various amino acids is described. We have bio‐evaluated the compounds against both chloroquine‐sensitive (3D7) and chloroquine‐resistant (K1) strains of Plasmodium falciparum in vitro. Among the series, compounds 4 and 7 exhibited 1.8‐ and 10.6‐fold superior activity as compared to chloroquine (CQ; IC50 = 0.255 ± 0.049 μm) against the K1 strain with IC50 values 0.137 ± 0.014 and 0.026 ± 0.007 μm, respectively. Furthermore, compound 7 also displayed promising activity against the 3D7 strain (IC50 = 0.024 ± 0.003 μm) of P. falciparum when compared to CQ. All the compounds in the series displayed resistance factor between 0.57 and 4.71 as against 51 for CQ. These results suggest that bisquinolines can be explored for further development as new antimalarial agents active against chloroquine‐resistant P. falciparum.
Children with medical complexity: a scoping review of interventions to support caregiver stress
Authors: Edelstein H. , Schippke J. , Sheffe S. , Kingsnorth S. 
Published: November 2016

AbstractBackgroundCaring for children with chronic and complex medical needs places extraordinary stress on parents and other family members. A scoping review was undertaken to identify and describe the full range of current interventions for reducing caregiver stress.MethodsApplying a broad definition of caregiver stress, a systematic search of three scientific databases (CINAHL, Embase and Ovid Medline), a general internet search and hand searching of key peer‐reviewed articles were conducted. Inclusion criteria were as follows: (i) published in English between 2004–2016; (ii) focused on familial caregivers, defined as parents, siblings or extended family; (iii) targeted children/youth with medical complexity between the ages of 1–24 years; and (iv) described an intervention and impact on caregiver stress. Data on type of intervention, study design and methods, measures and overall findings were extracted.ResultsForty‐nine studies were included from a list of 22 339 unique titles. Six domains of interventions were found: care coordination models (n = 23); respite care (n = 8); telemedicine (n = 5); peer and emotional support (n = 6); insurance and employment benefits (n = 4); and health and related supports (n = 3). Across studies, there was a wide variety of designs, outcomes and measures used.ConclusionsPositive findings of reductions in caregiver stress were noted within an emerging body of evidence on effective interventions for families of children with medical complexity. A commonality across domains was a significant focus on streamlining services and reducing the burden of care related to varied pressures experienced, including time, finances, care needs and service access, among others. There was non‐conclusive evidence however around which of the six identified intervention domains or combination thereof are most effective for reducing stress. These promising findings demonstrate that stress reduction is possible with the right support and that multiple interventions may be effective in reducing burdens of care experienced by families of children with medical complexity.
Completeness and correctness of cerebral palsy diagnoses in two health registers: implications for estimating prevalence
Authors: Hollung Sandra Julsen , Vik Torstein , Wiik Robert , Bakken Inger Johanne , Andersen Guro L 
Published: November 2016

AimTo assess completeness and correctness of cerebral palsy (CP) diagnoses in the Cerebral Palsy Register of Norway (CPRN) and the Norwegian Patient Register (NPR), and to estimate CP prevalence.MethodAmong 747 883 Norwegian residents born from 1996 to 2007, 2231 had a diagnosis of CP in the NPR while 1441 were registered in the CPRN. Children registered in the CPRN were considered to have a valid CP diagnosis. For those with a diagnosis of CP only in the NPR, two paediatricians reviewed the hospital records. The prevalence rate of CP with 95% confidence intervals (CI) was calculated on the basis of the combined data sets.ResultsOne thousand three hundred and ninety‐eight children were registered with a diagnosis of CP in both registers, 43 children were only registered in the CPRN, and 824 only in the NPR. The review of hospital records revealed that 464 (59.5%) had CP. Thus, the NPR was 98% complete, and for 86% the diagnosis was correct. The completeness of the CPRN was 76%, while the diagnosis was considered correct for all children (100%). The resulting prevalence of CP was 2.5 (95% CI 2.4–2.7) per 1000.InterpretationTo gain accurate estimates of prevalence rates of CP, it is essential to combine data sources and to validate register data.
Speech and language interventions for infants aged 0 to 2 years at high risk for cerebral palsy: a systematic review
Authors: Chorna Olena , Hamm Ellyn , Cummings Caitlin , Fetters Ashley , Maitre Nathalie L 
Published: November 2016

AimWe evaluated the level of evidence of speech, language, and communication interventions for infants at high‐risk for, or with a diagnosis of, cerebral palsy (CP) from 0 to 2 years old.MethodWe performed a systematic review of relevant terms. Articles were evaluated based on the level of methodological quality and evidence according to A Measurement Tool to Assess Systematic Reviews (AMSTAR) and Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines.ResultsThe search terms provided 17 publications consisting of speech or language interventions. There were no interventions in the high level of evidence category. The overall level of evidence was very low. Promising interventions included Responsivity and Prelinguistic Milieu Teaching and other parent–infant transaction frameworks.InterpretationThere are few evidence‐based interventions addressing speech, language, and communication needs of infants and toddlers at high risk for CP, and none for infants diagnosed with CP. Recommendation guidelines include parent–infant transaction programs.
Defending the Weak: Parental Defense Peaks When Chick Vulnerability is Greatest in the Herring Gull (Larus argentatus)
Authors: Crisologo Taylor L. , Bonter David N. 
Published: November 2016

AbstractSuccessful reproduction often depends upon parents providing offspring with resources and protection. In birds, reproductive success can often be enhanced by parents engaging in antipredator behaviors, but these behaviors can be costly. Theoretically, individuals should temporally modify the intensity of nest defense behavior to balance the costs and benefits of current and future reproductive success. More specifically, nest defense should vary throughout a nesting attempt to maximize fitness of the adults. Here, we consider the relationship between nest defense behavior and chick vulnerability in the herring gull (Larus argentatus), where chicks are under high predation risk. We estimated chick vulnerability by quantifying survival probabilities at different periods of the nestling stage. Simultaneously, we quantified changes in parental aggression throughout the nesting cycle by simulating predation attempts using a human predator model. We found that chick survival probabilities were lowest (i.e., vulnerability was highest) and parental aggression in nest defense was greatest during the first 10 days after hatching. Thus, we show that parents are most defensive when chicks are most vulnerable and that adults optimize nest defense behaviors in a way that maximizes their fitness.
Fracture toughness and fatigue crack growth rate properties in wire + arc additive manufactured Ti‐6Al‐4V
Authors: Zhang X , Martina F , Ding J , Wang X , Williams SW 
Published: November 2016

AbstractThis paper presents an experimental investigation of the fracture and fatigue crack growth properties of Ti‐6Al‐4V produced by the Wire + Arc Additive Manufacture (WAAM®) process. First, fracture toughness was measured for two different orientations with respect to the build direction; the effect of wire oxygen content and build strategy were also evaluated in the light of microstructure examination. Second, fatigue crack growth rates were measured for fully additive manufactured samples, as well as for samples containing an interface between WAAM® and wrought materials. The latter category covers five different scenarios of crack location and orientation with respect to the interface. Fatigue crack growth rates are compared with that of the wrought or WAAM® alone conditions. Crack growth trajectory of these tests is discussed in relation to the microstructure characteristics.
The influence of sediment mobility and channel geomorphology on periphyton abundance
Authors: Hoyle Joanna T. , Kilroy Cathy , Hicks D. Murray , Brown Logan 
Published: November 2016

Summary

River managers currently have difficulty predicting the combined effects of changes in flow regime and nutrients on periphyton biomass. Biomass accumulation is known to be promoted by increasing nutrients, light and temperature, and its loss has been related to invertebrate grazing and hydrological disturbance. However, biomass predictors that are reliable across a range of rivers have proven elusive. One possible contributing reason is that disturbance thresholds used in predictive models are typically linked to flow metrics, whereas the mechanisms for periphyton removal (current drag, abrasion and molar action by mobile sediment) relate more directly to hydraulic and geomorphic conditions.

We explored this possibility by relating periphyton removal events to hydraulic thresholds for sediment entrainment in 18 gravel‐ to boulder‐bed river reaches at which periphyton cover and nutrient concentrations had been regularly monitored. We converted observed threshold discharges for periphyton removal into shear stress thresholds using hydraulic models.

Our results demonstrate that: (i) abrasion by finer fractions of the bed material (2–16 mm) was the dominant physical mechanism removing periphyton; (ii) the frequency of mobility of this fine bed material was the dominant control on periphyton abundance and (iii) growth‐promoting variables, such as nutrient concentrations, tended to only become important to periphyton abundance when the frequency of sediment movement was low.

These findings highlight the importance of geomorphic differences between sites and explain why a single flow metric may be a poor predictor of periphyton abundance across geomorphically different rivers. Our analysis suggests that partitioning sites based on frequency of sediment mobility (either sand or the D50) could improve predictability of sites at which there is potential for nuisance levels of periphyton to develop.
Estuary–ocean connectivity: fast physics, slow biology
Authors: Raimonet Mélanie , Cloern James E. 
Published: November 2016

AbstractEstuaries are connected to both land and ocean so their physical, chemical, and biological dynamics are influenced by climate patterns over watersheds and ocean basins. We explored climate‐driven oceanic variability as a source of estuarine variability by comparing monthly time series of temperature and chlorophyll‐ainside San Francisco Bay with those in adjacent shelf waters of the California Current System (CCS) that are strongly responsive to wind‐driven upwelling. Monthly temperature fluctuations inside and outside the Bay were synchronous, but their correlations weakened with distance from the ocean. These results illustrate how variability of coastal water temperature (and associated properties such as nitrate and oxygen) propagates into estuaries through fast water exchanges that dissipate along the estuary. Unexpectedly, there was no correlation between monthly chlorophyll‐avariability inside and outside the Bay. However, at the annual scale Bay chlorophyll‐awas significantly correlated with the Spring Transition Index (STI) that sets biological production supporting fish recruitment in theCCS. Wind forcing of theCCSshifted in the late 1990s when theSTIadvanced 40 days. This shift was followed, with lags of 1–3 years, by 3‐ to 19‐fold increased abundances of five ocean‐produced demersal fish and crustaceans and 2.5‐fold increase of summer chlorophyll‐ain the Bay. These changes reflect a slow biological process of estuary–ocean connectivity operating through the immigration of fish and crustaceans that prey on bivalves, reduce their grazing pressure, and allow phytoplankton biomass to build. We identified clear signals of climate‐mediated oceanic variability in this estuary and discovered that the response patterns vary with the process of connectivity and the timescale of ocean variability. This result has important implications for managing nutrient inputs to estuaries connected to upwelling systems, and for assessing their responses to changing patterns of upwelling timing and intensity as the planet continues to warm.
Impact of sampling and storage technique, and duration of storage, on the composition of fresh grass when analysed using near‐infrared reflectance spectroscopy
Authors: Dale A. J. , Gordon A. W. , Archer J. , Ferris C. P. 
Published: November 2016

AbstractThe objective of this study was to examine the effect of sampling technique (pluck or cut), storage duration (immediate analysis, 24‐h or 48‐h), storage temperature (ambient or chilled) and storage conditions (air present, air excluded or breathable) on the composition of fresh grass sampled from a sward managed to simulate grazing. Treatments were repeated across four sampling dates, with grass samples stored in grip seal bags prior to analysis using near‐infrared reflectance spectroscopy. Grass sampled by ‘pluck’ had a higher crude protein and ME content, and a lower acid detergent fibre (ADF) content, compared to that sampled by ‘cut’. Grass stored for 48 h had a lower water soluble carbohydrate (WSC) and ME content and a higher ADF content than for immediate analysis. Samples stored for 24 h did not differ from immediate analysis. Grass stored at ambient temperature had a lower WSC and ME content compared to immediate analysis. Grass stored under ‘breathable’ conditions had a lower ME content and higher ADF content than immediate analysis or samples stored with air present or air excluded. It is recommended that grass for analysis should be sampled by cutting, stored chilled (4°C) in a sealed bag to minimize exposure to oxygen and analysed within 24 h of harvest.
Selections Before the Selection: Earnings Advantages of Immigrants Who Were Former Skilled Temporary Foreign Workers in Canada
Authors: Hou Feng , Bonikowska Aneta 
Published: November 2016

This study examines the earnings advantage of economic immigrants who initially arrived as temporary foreign workers (TFWs) over immigrants who were directly selected from abroad. Using the Longitudinal Immigration Database, this study finds that skilled versus non‐skilled prior Canadian work experience matters significantly to after‐immigration earnings. Former skilled TFWs had much higher initial earnings than immigrants who first arrived in Canada as landed immigrants. This earnings gap narrowed in the first 10 years but did not disappear. In comparison, former non‐skilled TFWs had significantly lower initial earnings and slower earnings growth than immigrants without prior Canadian experience.