bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Tale of One City: The Devo Manc Deal and Its Implications for English Devolution
Authors: Kenealy Daniel 
Published: July 2016

AbstractOn 2 November 2014 George Osborne stood in the impressive great council chamber of Manchester town hall and, flanked by the ten leaders of Greater Manchester's local authorities, announced a devolution deal for the city‐region. Greater Manchester would receive a significant package of powers over transport, housing, planning, skills, business support and welfare in exchange for creating new governance structures, including a directly elected mayor for the city‐region. This article explores the background to the Devo Manc deal, arguing that it is the product of both a long history of local government collaboration in Greater Manchester and George Osborne's desire for a sweeping restructure of English governance. It traces how the key decisions were taken quickly and by a small number of key officials. The article also identifies some flaws in Devo Manc and considers whether it is an appropriate model for other city‐regions in the UK.
Unknown unknowns: essential genes in quest for function
Authors: Danchin Antoine , Fang Gang 
Published: July 2016

SummaryThe experimental design of a minimal synthetic genome revealed the presence of a large number of genes without ascribed function, in part because the abstract laws of life must be implemented within ad hoc material contraptions. Creating a function needs recruitment of some pre‐existing structure and this reveals kludges in their set‐up and history. Here, we show that looking for functions as an engineer would help in discovery of a significant number of those, proposed together with conceptual handles allowing investigators to pursue this endeavour in other contexts.
Proof‐of‐Concept Study to Assess the Nociceptin Receptor Antagonist LY2940094 as a New Treatment for Alcohol Dependence
Authors: Post Anke , Smart Trevor S. , Jackson Kimberley , Mann Joanne , Mohs Richard , Rorick‐Kehn Linda , Statnick Michael , Anton Raymond , O'Malley Stephanie S. , Wong Conrad J. 
Published: July 2016

BackgroundThis was a proof‐of‐concept study to evaluate the efficacy of LY2940094, a nociceptin/orphanin FQ peptide receptor antagonist, in reducing alcohol consumption in actively alcohol‐drinking patients with alcohol dependence.MethodsEighty‐eight patients, 21 to 66 years of age, diagnosed with alcohol dependence, reporting 3 to 6 heavy drinking days per week, were randomized (1:1) to 8 weeks of treatment with once‐daily oral placebo (N = 44) or 40 mg/d of LY2940094 (N = 44). The primary efficacy analysis was the change from baseline in number of drinks per day (NDD) utilizing mixed‐model repeated measures comparing LY2940094 and placebo in Month 2 of the 8‐week double‐blind treatment period. The probability that the difference relative to placebo in NDD was ≤0 at endpoint was calculated, and a probability ≥80% was considered to be evidence that LY2940094 was associated with the reduction in NDD.ResultsAfter 8 weeks of treatment, reduction in mean NDD did not differ between LY2940094 versus placebo (−1.4 vs. −1.5, respectively, 44% probability of greater reduction relative to placebo), but there was a greater reduction in the mean percentage of heavy drinking days in a month with LY2940094 versus placebo (−24.5 vs. −15.7%, respectively, 93% probability of a greater reduction relative to placebo), and an increase in the mean percentage of abstinent days in a month compared to placebo (9.1 vs. 1.9%, respectively, 91% probability of a greater increase relative to placebo). Patients who were treated with LY2940094 showed decreased plasma levels of gamma‐glutamyl transferase with probabilities ≥98% for greater reduction compared with placebo at Weeks 1, 4, 6, and 8. Treatment‐emergent adverse events in ≥5% of patients treated with LY2940094 included insomnia, vomiting, and anxiety. There were no serious adverse events or significant changes in laboratory assessments or vital signs with LY2940094.ConclusionsAlthough not reducing the NDD, LY2940094, compared to placebo, did reduce heavy drinking days and increased abstinence days in patients with alcohol dependence.
Effect of polymorphisms in the CAMKMT gene on growth traits in Ujumqin sheep
Authors: Ma Xiaomeng , Guan Long , Xuan Junli , Wang Huihua , Yuan Zehu , Wu Mingming , Liu Ruizao , Zhu Caiye , Wei Caihong , Zhao Fuping , Du Lixin , Zhang Li 
Published: July 2016

SummaryOur previous genome‐wide association study in sheep revealed that OAR3‐84073899.1 (SNP31) in intron 8 of the CAMKMT gene was significantly associated with post‐weaning gain at the genomic level. Herein, we performed a replication study to investigate single nucleotide polymorphisms (SNPs) within the CAMKMT gene exons, and 1000 bp of the 5′‐ and 3′‐intranslated regions (UTRs) and their associations with growth traits in Ujumqin sheep. Five SNPs were identified through DNA pool sequencing technology: SNP26 in the 5′‐UTR, SNP06 in exon 5, SNP07 in exon 8 and SNP27 and SNP28 in the 3′‐UTR. Six SNPs, including SNP31 in intron 8, were genotyped in the validation group of 343 Ujumqin sheep, and each SNP was classified into three genotypes. The chi‐square test suggested that all the variations were in Hardy–Weinberg equilibrium (P > 0.05) except for SNP28 and SNP31. Linkage disequilibrium analysis showed that SNP07 and SNP31 were strongly linked. An association analysis suggested that SNP06 was significantly associated with chest girth at 6 months of age (P < 0.05). SNP07 exhibited significant correlation with body weight and chest girth at 4 months of age and with body weight, chest girth and chest width at 6 months of age (P < 0.05). SNP27 was highly associated with body weight and chest girth at 4 months of age (P < 0.05), and SNP28 was extremely significantly associated with body weight and chest girth at 4 months of age and with chest girth at 6 months of age (P < 0.01). SNP31 was significantly associated with body weight and shin circumference at 4 months of age and with post‐weaning gain (P < 0.05). Association analysis of the combined effect of SNP07 and SNP31 showed significant correlation with body weight and chest girth at four of months of age (P < 0.05) and with body weight and chest girth at 6 months of age (P < 0.05). These results indicate that the SNPs could be used as meritorious and available genetic markers in growth traits breeding and that the CAMKMT gene may be one of the key candidate genes that affect Ujumqin economic traits.
Head and neck adaptive radiotherapy: Predicting the time to replan
Authors: Brown Elizabeth , Owen Rebecca , Harden Fiona , Mengersen Kerrie , Oestreich Kimberley , Houghton Whitney , Poulsen Michael , Harris Selina , Lin Charles , Porceddu Sandro 
Published: July 2016

AbstractAimHead and neck (H&N) cancer patients can undergo anatomical change throughout radiotherapy treatment. Adaptive radiotherapy (ART) is effective in addressing the impact of this change on the planned dose distribution. The aim of this study was to identify pretreatment factors that influence the need for and timing of replanning for patients receiving chemoradiotherapy for node‐positive nasopharyngeal (NPC) and oropharyngeal carcinoma (OPC).MethodsOf 110 patients enrolled in a prospective H&N ART study, 21 (19%) underwent a second planning scan (re‐CT) and were included in this review. Univariate and multivariate analysis was used to compare those patients who were replanned with those that were not. Factors influencing the timing of replanning were assessed including patient and tumor characteristics and structure volume details.ResultsOf the five replanned patients, three were diagnosed with NPC (P = 0.06) and had significantly larger initial nodal volumes (median volume 140.3 cc vs. 39.1 cc, P = 0.019). Overall the median time of re‐CT was significantly different between replanned and non‐replanned patients, with replanned patients having an earlier re‐CT: median fraction 18 versus fraction 23 (P = 0.01). Specifically, NPC patients who were replanned had a re‐CT performed earlier than OPC patients (median fraction 11 vs. 20).ConclusionFor H&N patients with large nodes receiving definitive chemoradiotherapy, replanning may be considered at the commencement of week 3 for NPC patients and in week 4 of treatment for OPC patients. This information may facilitate a forward planning approach to H&N ART that enables allocation of departmental resources prior to treatment commencement.
Glucagon‐like peptide‐1 receptor signalling reduces microvascular thrombosis, nitro‐oxidative stress and platelet activation in endotoxaemic mice
Authors: Steven Sebastian , Jurk Kerstin , Kopp Maximilian , Kröller‐Schön Swenja , Mikhed Yuliya , Schwierczek Kathrin , Roohani Siyer , Kashani Fatemeh , Oelze Matthias , Klein Thomas , Tokalov Sergey , Danckwardt Sven , Strand Susanne , Wenzel Philip , Münzel Thomas , Daiber Andreas 
Published: July 2016

AbstractBackground and PurposeExcessive inflammation in sepsis causes microvascular thrombosis and thrombocytopenia associated with organ dysfunction and high mortality. The present studies aimed to investigate whether inhibition of dipeptidyl peptidase‐4 (DPP‐4) and supplementation with glucagon‐like peptide‐1 (GLP‐1) receptor agonists improved endotoxaemia‐associated microvascular thrombosis via immunomodulatory effects.Experimental ApproachEndotoxaemia was induced in C57BL/6J mice by a single injection of LPS (17.5 mg kg‐1 for survival and 10 mg kg‐1 for all other studies). For survival studies, treatment was started 6 h after LPS injection. For all other studies, drugs were injected 48 h before LPS treatment.Key ResultsMice treated with LPS alone showed severe thrombocytopenia, microvascular thrombosis in the pulmonary circulation (fluorescence imaging), increased LDH activity, endothelial dysfunction and increased markers of inflammation in aorta and whole blood (leukocyte‐dependent oxidative burst, nitrosyl‐iron haemoglobin, a marker of nitrosative stress, and expression of inducible NOS). Treatment with the DPP‐4 inhibitor linagliptin or the GLP‐1 receptor agonist liraglutide, as well as genetic deletion of DPP‐4 (DPP4−/− mice) improved all these parameters. In GLP‐1 receptor‐deficient mice, both linagliptin and liraglutide lost their beneficial effects and improvement of prognosis. Incubation of platelets and cultured monocytes (containing GLP‐1 receptor protein) with GLP‐1 receptor agonists inhibited the monocytic oxidative burst and platelet activation, with a GLP‐1 receptor‐dependent elevation of cAMP levels and PKA activation.Conclusions and ImplicationsGLP‐1 receptor activation in platelets by linagliptin and liraglutide strongly attenuated endotoxaemia‐induced microvascular thrombosis and mortality by a cAMP/PKA‐dependent mechanism, preventing systemic inflammation, vascular dysfunction and end organ damage.Linked ArticlesThis article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc
Innovations in Practice: Evaluating clinical outcome and service utilization in an AMBIT‐trained Tier 4 child and adolescent mental health service
Authors: Griffiths Helen , Noble Abbi , Duffy Fiona , Schwannauer Matthias 
Published: July 2016

BackgroundTo present clinical outcome data of the Adolescent Mentalization‐based Integrative Treatment (AMBIT)‐trained NHS Lothian Tier 4 child and adolescent mental health service in the context of service utilization and engagement.MethodData were obtained for a 2‐year period that included details of all face‐to‐face contacts between young people and clinicians along with routinely collected clinical outcomes data relating to anxiety, depression, symptoms of psychosis and quality of life.ResultsImprovements were observed in quality of life, symptoms and distress across the course of the intervention. Overall attendance rates were high (80%). Relative to those who were better engaged, the less well‐engaged group received the same number of appointments but spent longer in the service (χ2(1) = 5.26, p = .022), had more professionals involved in their care (χ2(1) = 4.91, p = .027) and showed a nonsignificant trend to more inpatient admissions. Later engagement was not associated with distress or symptoms at entry into the service with the exception of negative symptoms in the Early Psychosis Support Service cohort. Age and two quality of life factors were associated with later engagement (p < .05).ConclusionsOur AMBIT‐trained Tier 4 CAMH service demonstrates change over the course of intervention consistent with the service model's theoretical expectations. Engagement with the service may be associated more with factors related to social circumstance and functioning than with key symptoms and distress. Less well‐engaged young people utilize increased service resource. AMBIT's mentalizing focus may improve service provision for young people who are poorly engaged with mental health services.
Memory‐Based Simple Heuristics as Attribute Substitution: Competitive Tests of Binary Choice Inference Models
Authors: Honda Hidehito , Matsuka Toshihiko , Ueda Kazuhiro 
Published: July 2016

AbstractSome researchers on binary choice inference have argued that people make inferences based on simple heuristics, such as recognition, fluency, or familiarity. Others have argued that people make inferences based on available knowledge. To examine the boundary between heuristic and knowledge usage, we examine binary choice inference processes in terms of attribute substitution in heuristic use (Kahneman & Frederick, 2005). In this framework, it is predicted that people will rely on heuristic or knowledge‐based inference depending on the subjective difficulty of the inference task. We conducted competitive tests of binary choice inference models representing simple heuristics (fluency and familiarity heuristics) and knowledge‐based inference models. We found that a simple heuristic model (especially a familiarity heuristic model) explained inference patterns for subjectively difficult inference tasks, and that a knowledge‐based inference model explained subjectively easy inference tasks. These results were consistent with the predictions of the attribute substitution framework. Issues on usage of simple heuristics and psychological processes are discussed.
The non‐motor side of the honeymoon period of Parkinson's disease and its relationship with quality of life: a 4‐year longitudinal study
Authors: Erro R. , Picillo M. , Vitale C. , Amboni M. , Moccia M. , Santangelo G. , Pellecchia M. T. , Barone P. 
Published: July 2016

Background and purposeVery little is known about the progression of non‐motor symptoms (NMSs) in Parkinson's disease (PD) and there are no longitudinal studies exploring this topic from the earliest stage, when patients receive the diagnosis. We here report on the progression of NMSs over 4 years from diagnosis in a cohort of de‐novo, previously untreated, patients with PD.MethodsConsecutive de‐novo (disease duration < 2 years), untreated patients with PD were enrolled in this observational study. Evaluations were then scheduled every 2 years and included assessment of motor and non‐motor features as well as of quality of life measures.ResultsSixty‐one patients were prospectively followed‐up for 4 years from diagnosis. The majority of NMSs increased over time and significantly affected quality of life, whereas motor disability did not. There was no significant association between NMSs and dopaminergic therapy in terms of both drug class and total levodopa‐equivalent daily dosage. Excessive daytime sleepiness was the only NMS correlating with therapy with dopamine agonists. Female patients were more likely to have worse quality of life.ConclusionsNon‐motor symptoms significantly increase over time, with a different progression rate for each one. NMSs significantly affect quality of life in PD and we here demonstrated that this was especially the case when patients were in their (motor) honeymoon period. Future trials should target non‐dopaminergic networks and consider NMSs in their outcomes.
Stomatal response to humidity and CO2 implicated in recent decline in US evaporation
Authors: Rigden Angela J. , Salvucci Guido D. 
Published: July 2016

AbstractEvapotranspiration, defined as the total flux of water from the land surface to the atmosphere, is a major component of the hydrologic cycle and surface energy balance. Although evapotranspiration is expected to intensify with increasing temperatures, long‐term, regional trends in evapotranspiration remain uncertain due to spatially and temporally limited direct measurements. In this study, we utilize an emergent relation between the land surface and atmospheric boundary layer to infer daily evapotranspiration from historical meteorological data collected at 236 weather stations across the United States. Our results suggest a statistically significant (α = 0.05) decrease in evapotranspiration of approximately 6% from 1961 to 2014, with a significant (α = 0.05) sharp decline of 13% from 1998 to 2014. We attribute the decrease in evapotranspiration mostly to declines in surface conductance, but also to offsetting changes in longwave radiation, wind speed, and incoming solar radiation. Using an established stomatal conductance model, we explain the changes in inferred surface conductance as a response to increases in carbon dioxide and, more recently, to an abrupt decrease in atmospheric humidity.
An ecoregion assessment of projected tree species vulnerabilities in western North America through the 21st century
Authors: Mathys Amanda S. , Coops Nicholas C. , Waring Richard H. 
Published: July 2016

AbstractForest ecosystems across western North America will likely see shifts in both tree species dominance and composition over the rest of this century in response to climate change. Our objective in this study was to identify which ecological regions might expect the greatest changes to occur. We used the process‐based growth model 3‐PG, to provide estimates of tree species responses to changes in environmental conditions and to evaluate the extent that species are resilient to shifts in climate over the rest of this century. We assessed the vulnerability of 20 tree species in western North America using the Canadian global circulation model under three different emission scenarios. We provided detailed projections of species shifts by including soil maps that account for the spatial variation in soil water availability and soil fertility as well as by utilizing annual climate projections of monthly changes in air temperature, precipitation, solar radiation, vapor pressure deficit and frost at a spatial resolution of one km. Projected suitable areas for tree species were compared to their current ranges based on observations at >40 000 field survey plots. Tree species were classified as vulnerable if environmental conditions projected in the future appear outside that of their current distribution ≥70% of the time. We added a migration constraint that limits species dispersal to <200 m yr−1 to provide more realistic projections on species distributions. Based on these combinations of constraints, we predicted the greatest changes in the distribution of dominant tree species to occur within the Northwest Forested Mountains and the highest number of tree species stressed will likely be in the North American Deserts. Projected climatic changes appear especially unfavorable for species in the subalpine zone, where major shifts in composition may lead to the emergence of new forest types.
Towards Miscanthus combustion quality improvement: the role of flowering and senescence
Authors: Jensen Elaine , Robson Paul , Farrar Kerrie , Thomas Jones Sian , Clifton‐Brown John , Payne Roger , Donnison Iain 
Published: July 2016

AbstractIn commercially grown Miscanthus × giganteus, despite imposing a yield penalty, postwinter harvests improve quality criteria for thermal conversion and crop sustainability through remobilization of nutrients to the underground rhizome. We examined 16 Miscanthus genotypes with different flowering and senescence times for variation in N, P, K, moisture, ash, Cl and Si contents, hypothesizing that early flowering and senescence could result in improved biomass quality and/or enable an earlier harvest of biomass (in autumn at peak yield). Ideal crop characteristics at harvest are low N and P to reduce future fertilizer inputs, low K and Cl to reduce corrosion in boilers, low moisture to reduce spoilage and transportation costs, and low Si and ash to reduce slagging and consequent operational downtime. Stems and leaves were harvested during summer, autumn and then the following spring after overwinter ripening. In spring, stem contents of N were 30–60 mg kg−1, P were 203–1132 mg kg−1, K were 290–4098 mg kg−1, Cl were 10–23 mg kg−1 and moisture were 12–38%. Notably, late senescence resulted in increased N, P, K, Cl, moisture and ash contents, and should therefore be avoided for thermochemical conversion. Flowering and senescence led to overall improved combustion quality, where flowered genotypes tended towards lower P, K, Cl and moisture contents; marginally less, or similar, N, Si and ash contents; and a similar higher heating value, compared to those that had not flowered. Such genotypes could potentially be harvested in the autumn. However, one genotype that did not flower in our trial exhibited sufficiently low N and K content in autumn to meet the ENplus wood pellet standards for those traits, and some of the lowest P, moisture and ash contents in our trial, and is thus a target for future research and breeding.
Evaluation of three fully automated immunoassay systems for detection of IgA anti‐beta 2‐glycoprotein I antibodies
Authors: Pérez D. , Martínez‐Flores J. A. , Serrano M. , Lora D. , Paz‐Artal E. , Morales J. M. , Serrano A. 
Published: July 2016

SummaryIntroductionIn recent years, we have been witnessing increased clinical interest in the determination of IgA anti‐beta 2‐glycoprotein I (aB2GPI) antibodies as well as increased demand for this test. Some ELISA‐based diagnostic systems for IgA aB2GPI antibodies detection are suboptimal to detect it. The aim of our study was to determine whether the diagnostic yield of modern detection systems based on automatic platforms to measure IgA aB2GPI is equivalent to that of the well‐optimized ELISA‐based assays.MethodsIn total, 130 patients were analyzed for IgA aB2GPI by three fully automated immunoassays using an ELISA‐based assay as reference. The three systems were also analyzed for IgG aB2GPI with 58 patients.ResultsSystem 1 was able to detect IgA aB2GPI with good sensitivity and kappa index (99% and 0.72, respectively). The other two systems had also poor sensitivity (20% and 15%) and kappa index (0.10 and 0.07), respectively. On the other hand, kappa index for IgG aB2GPI was >0.89 in the three systems.ConclusionSome analytical methods to detect IgA aB2GPI are suboptimal as well as some ELISA‐based diagnostic systems. It is important that the scientific community work to standardize analytical methods to determine IgA aB2GPI antibodies.