bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methods for the economic evaluation of changes to the organisation and delivery of health services: principal challenges and recommendations
Authors: Meacock Rachel 
Published: April 2018

AbstractThere is a requirement for economic evaluation of health technologies seeking public funding across Europe. Changes to the organisation and delivery of health services, including changes to health policy, are not covered by such appraisals. These changes also have consequences for National Health Service (NHS) funds, yet undergo no mandatory cost-effectiveness assessment. The focus on health technologies may have occurred because larger-scale service changes pose more complex challenges to evaluators. This paper discusses the principal challenges faced when performing economic evaluations of changes to the organisation and delivery of health services and provides recommendations for overcoming them. The five principal challenges identified are as follows: undertakingex-anteevaluation; evaluating impacts in terms of quality-adjusted life years; assessing costs and opportunity costs; accounting for spillover effects; and generalisability. Of these challenges, methods for estimating the impact on costs and quality-adjusted life years are those most in need of development. Methods are available forex-anteevaluation, assessing opportunity costs and examining generalisability. However, these are rarely applied in practice. The general principles of assessing the cost-effectiveness of interventions should be applied to all NHS spending, not just that involving health technologies. Advancements in this area have the potential to improve the allocation of scarce NHS resources.
Solar EUV Flux Proxy Using Multifrequency Solar Radio Flux
Authors: Zhang Yongliang , Paxton Larry J. 
Published: April 2018

AbstractWe report a new solar extreme ultraviolet (EUV; 26–34 nm) proxy using solar radio fluxes at six different frequencies (410; 610; 1,415; 2,695; 4,995; and 8,800 MHz) from ground‐based observations. The radio fluxes (2002–2008) are used to estimate the solar EUV flux under nonsolar flare conditions through an artificial neural network trained with coincidently observed solar EUV (26–34 nm) fluxes from the SOlar and Heliospheric Observatory/Solar EUV Monitor instrument. The radio fluxes at 610; 1,415; and 8,800 MHz are the three top contributors in the estimation of the solar EUV flux. The 1,415 MHz flux has the highest correlation coefficient (0.97) with the observed EUV flux. The estimated EUV flux retained the highest correlation coefficient (0.97) and had the lowest error in comparison with the observed EUV flux. The popular F10.7cm (2,800 MHz) is between 2,695 and 4,995 MHz, which have a minor contribution to the estimated EUV flux. On the other hand, F30cm (1,000 MHz) is between 610 and 1,415 MHz, the two major contributors to the estimated EUV flux. These features are consistent with a significantly better neutral density modeling using F30cm versus F10.7cm (Bruinsman, 2015, https://doi.org/10.1051/swsc/2015001). Similar results are obtained by applying the coefficients trained using a subset of the radio data (2002, 2004, and 2007) to a different subset of the data (2003, 2005, 2006, and 2008). These indicate that solar radio fluxes at multiple frequencies can be used to reliably retrieve solar EUV flux, one of the key parameters for space weather studies.
Lajishankou Ophiolite Complex: Implications for Paleozoic Multiple Accretionary and Collisional Events in the South Qilian Belt
Authors: Fu Changlei , Yan Zhen , Wang Zongqi , Buckman Solomon , Aitchison Jonathan C. , Niu Manlan , Cao Bo , Guo Xianqing , Li Xiucai , Li Yunshuai , Li Jiliang 
Published: April 2018

AbstractThe Lajishan ophiolite complex in the Qilian Orogen is one of several ophiolites situated between the Qaidam and North China blocks that record episodic closure of the Proto‐Tethyan Ocean. Detailed field relations and geochemical and geochronological studies are critical to unraveling the tectonic processes responsible for an extensive period of intraoceanic subduction that produced juvenile ophiolite/island arc terranes, which were obducted onto continental margins during ocean closure. The Lajishankou ophiolite complex crops out along the northern margin of the South Qilian belt and was thrust over a Neoproterozoic‐Ordovician passive margin sequence that was deposited upon the Proterozoic Central Qilian block. The mafic rocks in Lajishankou ophiolite complex are the most abundant slices and can be categorized into three distinct groups based on petrological, geochemical, and geochronological characteristics: massive island arc tholeiites, 509‐Ma back‐arc dolerite dykes, and 491‐Ma pillow basaltic and dolerite slices that are of seamount origin in a back‐arc basin. These results, together with spatial relationships, indicate that the Cambrian island arc rocks, ophiolite complex, and accretionary complex developed between 530 and 480 Ma as a single, intraoceanic arc‐basin system as a result of south directed subduction of the Proto‐Tethyan Ocean prior to Early Ordovician obduction of this system onto the Central Qilian block. Final continental amalgamation involved continental collision of the Central Qilian block with the Qaidam block during the Late Ordovician. This model solves the long‐lasting discussion on the emplacement of the Lajishan ophiolite and contributes to an improved understanding of multiple accretionary and collisional processes in the Qilian Orogen.
Precambrian Tectonic Discontinuities in Western Laurentia: Broadband Seismological Perspectives on the Snowbird and Great Falls Tectonic Zones
Authors: Gu Yu Jeffrey , Chen Yunfeng , Dokht Ramin M. H. , Wang Ruijia 
Published: April 2018

AbstractThe Snowbird Tectonic Zone (STZ) in southwestern Canada and the Great Falls Tectonic Zone (GFTZ) in northern Montana are two structural lineaments with major implications for the formation and evolution of the western North American craton. In this study, we examine the origins of these two proposed Proterozoic sutures using broadband seismic data from Alberta and USArray stations. We find substantial spatial variations in crustal structure and thickness across both the STZ and GFTZ based on an integrated analysis of P‐to‐S receiver functions, shear velocities, and potential field measurements. The STZ marks the transition from deep (NW, ~44 km) to shallow (SE, ~39 km) Moho in central Alberta. This steep Moho relief, in conjunction with elevated Vp/Vs ratios, provide compelling evidence for Proterozoic subduction and magmatism. In northern Montana, the Moho is depressed by ~6 km within the fold‐and‐thrust belts of the Trans‐Montana Orogen, where high (>1.84) Vp/Vs ratios spread along the collisional suture of the Dillion Shear Zone and terminates sharply along the reworked margin of the Wyoming craton. These observations, coupled with widespread lower crustal conversions, are concordant with a Paleoproterozoic orogeny resulting from collision(s) between Archean cratons. On the other hand, a flat Moho under major northeast striking potential field lineaments in the northernmost Montana favors an origin as a ductile shear zone, rather than suture, in the orogenic hinterland. We find evidence for crustal underplating beneath the GFTZ, though this anomalous layer is smaller than previous estimates and appears to be confined to the Trans‐Montana Orogen.
A Middle Permian Ophiolitic Mélange Belt in the Solonker Suture Zone, Western Inner Mongolia, China: Implications for the Evolution of the Paleo‐Asian Ocean
Authors: Fu Dong , Huang Bo , Kusky Timothy M. , Li Gangzhu , Wilde Simon A. , Zhou Wenxiao , Yu Yang 
Published: April 2018

AbstractThe Solonker suture zone in the southeastern Central Asian Orogenic Belt is generally regarded as the location of the final closure of the Paleo‐Asian Ocean, formed by complex and cryptic accretionary processes during late Paleozoic to early Mesozoic times. We recognize three tectonically juxtaposed lithotectonic units, including forearc basin sedimentary sequences, ophiolitic fragments, and ophiolitic mélange in the Solonker area, and here investigate the structural and kinematic features of the ophiolitic mélange in detail. The Solonker ophiolitic mélange has typical block‐in‐matrix fabrics with variably sized basalt, chert, sandstone, and ultramafic blocks embedded in siliceous‐argillaceous and siltstone matrices. Both extensional and contractional structures are well developed within the mélange, characterized by pervasive foliation, pinch‐and‐swell, boudinage, and S‐C fabrics. Kinematic analysis of the deformation structures indicates top‐to‐the‐N thrusting, correlated with the southward subduction of the southern margin of the Paleo‐Asian Ocean. Zircon U‐Pb ages of the matrices and a tonalite pluton intruded into the mélange constrain the formation age of the Solonker ophiolitic mélange to be middle Permian (ca. 268–260 Ma). Geochemical data from the ophiolitic rocks show subduction‐related characteristics with enriched large ion lithophile elements and depleted Nb, implying formation in a forearc setting. Our study provides robust evidence for the closure time of the Paleo‐Asian Ocean after the middle Permian. The late‐stage evolution of the Paleo‐Asian Ocean was characterized by subduction, forearc accretion with subsequent obduction of the kilometer‐scale upper plate, and soft collision, ultimately leading to the formation of the Solonker suture zone in the North China‐Mongolia segment.
Emerging two-dimensional ferromagnetism in silicene materials
Authors: Tokmachev Andrey M. , Averyanov Dmitry V. , Parfenov Oleg E. , Taldenkov Alexander N. , Karateev Igor A. , Sokolov Ivan S. , Kondratev Oleg A. , Storchak Vyacheslav G. 
Published: April 2018

AbstractThe appeal of ultra-compact spintronics drives intense research on magnetism in low-dimensional materials. Recent years have witnessed remarkable progress in engineering two-dimensional (2D) magnetism via defects, edges, adatoms, and magnetic proximity. However, intrinsic 2D ferromagnetism remained elusive until recent discovery of out-of-plane magneto-optical response in Cr-based layers, stimulating the search for 2D magnets with tunable and diverse properties. Here we employ a bottom-up approach to produce layered structures of silicene (a Si counterpart of graphene) functionalized by rare-earth atoms, ranging from the bulk down to one monolayer. We track the evolution from the antiferromagnetism of the bulk to intrinsic 2D in-plane ferromagnetism of ultrathin layers, with its characteristic dependence of the transition temperature on low magnetic fields. The emerging ferromagnetism manifests itself in the electron transport. The discovery of a class of robust 2D magnets, compatible with the mature Si technology, is instrumental for engineering new devices and understanding spin phenomena.
Bcl11b is essential for licensing Th2 differentiation during helminth infection and allergic asthma
Authors: Lorentsen Kyle J. , Cho Jonathan J. , Luo Xiaoping , Zuniga Ashley N. , Urban Joseph F. , Zhou Liang , Gharaibeh Raad , Jobin Christian , Kladde Michael P. , Avram Dorina 
Published: April 2018

AbstractDuring helminth infection and allergic asthma, naive CD4+ T-cells differentiate into cytokine-producing Type-2 helper (Th2) cells that resolve the infection or induce asthma-associated pathology. Mechanisms regulating the Th2 differentiation in vivo remain poorly understood. Here we report that mice lacking Bcl11b in mature T-cells have a diminished capacity to mount Th2 responses during helminth infection and allergic asthma, showing reduced Th2 cytokines and Gata3, and elevated Runx3. We provide evidence that Bcl11b is required to maintain chromatin accessibility at Th2-cytokine promoters and locus-control regions, and binds the Il4 HS IV silencer, reducing its accessibility. Bcl11b also binds Gata3-intronic and downstream-noncoding sites, sustaining the Gata3 expression. In addition, Bcl11b binds and deactivates upstream enhancers at Runx3 locus, restricting the Runx3 expression and its availability to act at the Il4 HS IV silencer. Thus, our results establish novel roles for Bcl11b in the regulatory loop that licenses Th2 program in vivo.
Using chemical and DNA marker analysis to authenticate a high-value food, manuka honey
Authors: McDonald Claire M. , Keeling Suzanne E. , Brewer Mark J. , Hathaway Steve C. 
Published: April 2018

AbstractEnsuring the authenticity of food is a rapidly emerging issue, especially in regard to high-value products that are marketed through increasingly complex global food chains. With the ever-increasing potential for mislabeling, fraud and adulteration, governments are increasingly having to invest in, and assure, the authenticity of foods in international trade. This is particularly the case for manuka honey, an iconic New Zealand food product. We show how the authenticity of a specific type of honey can be determined using a combination of chemicals derived from nectar and DNA derived from pollen. We employ an inter-disciplinary approach to evaluate a selection of authenticity markers, followed by classification modelling to produce criteria that consistently identify manuka honey from New Zealand. The outcome of our work provides robust identification criteria that can be applied in a regulatory setting to authenticate a high-value natural food. Our approach can transfer to other foods where assurance of authenticity must take into account a high level of natural variability.
The ash dieback invasion of Europe was founded by two genetically divergent individuals
Authors: McMullan Mark , Rafiqi Maryam , Kaithakottil Gemy , Clavijo Bernardo J. , Bilham Lorelei , Orton Elizabeth , Percival-Alwyn Lawrence , Ward Ben J. , Edwards Anne , Saunders Diane G. O. , Garcia Accinelli Gonzalo , Wright Jonathan , Verweij Walter , Koutsovoulos Georgios , Yoshida Kentaro , Hosoya Tsuyoshi , Williamson Louisa , Jennings Philip , Ioos Renaud , Husson Claude , Hietala Ari M. , Vivian-Smith Adam , Solheim Halvor , MaClean Dan , Fosker Christine , Hall Neil , Brown James K. M. , Swarbreck David , Blaxter Mark , Downie J. Allan , Clark Matthew D. 
Published: April 2018

AbstractAccelerating international trade and climate change make pathogen spread an increasing concern. Hymenoscyphus fraxineus, the causal agent of ash dieback, is a fungal pathogen that has been moving across continents and hosts from Asian to European ash. Most European common ash trees (Fraxinus excelsior) are highly susceptible to H. fraxineus, although a minority (~5%) have partial resistance to dieback. Here, we assemble and annotate a H. fraxineus draft genome, which approaches chromosome scale. Pathogen genetic diversity across Europe and in Japan, reveals a strong bottleneck in Europe, though a signal of adaptive diversity remains in key host interaction genes. We find that the European population was founded by two divergent haploid individuals. Divergence between these haplotypes represents the ancestral polymorphism within a large source population. Subsequent introduction from this source would greatly increase adaptive potential of the pathogen. Thus, further introgression of H. fraxineus into Europe represents a potential threat and Europe-wide biological security measures are needed to manage this disease.
Integrative metabolic and microbial profiling on patients with Spleen-yang-deficiency syndrome
Authors: Lin Zhang , Ye Wu , Zu Xianpeng , Xie Haisheng , Li Houkai , Li Yiping , Zhang Weidong 
Published: April 2018

AbstractGut microbiota is recognized as an indispensable “metabolic organ” that plays crucial roles in maintaining human health or initiating diseases. Spleen-yang-deficiency syndrome (SYDS) is a common syndrome of Traditional Chinese Medicine (TCM) clinic. It is a complex phenotype reflecting the overall changes of metabolism which are mainly caused by digestive disorders. However, little is known about the changes of gut microbiota and metabolism in patients with SYDS, as well as the crosstalk between gut microbiota and host metabolism. In the current study, an integrative metabolic and microbial profiling was performed on plasma, urine and feces from recruited SYDS and healthy individuals by using a LC-QTOFMS-based metabolomic and 16 s rRNA sequencing approaches. Our results showed a potentially significant contribution of gut dysbiosis to the metabolic disorders in SYDS. By integrating the differential gut bacteria with the metabolites, the results revealed some active bacterium of norank_f_CFT112H7, f_lachnospiraceae and bacteroides were closely involved in host mucosal integrity, bile acid metabolism and polysaccharides decomposition. Therefore, our results indicated the probable involvement of gut microbiota in mediating the metabolic changes, which warrants a further investigation on the role of gut microbiota in modulating the pathogenesis of SYDS.
Elovl6 is a negative clinical predictor for liver cancer and knockdown of Elovl6 reduces murine liver cancer progression
Authors: Su Yu-Chu , Feng Yin-Hsun , Wu Hung-Tsung , Huang Yao-Shen , Tung Chao-Ling , Wu Pensee , Chang Chih-Jen , Shiau Ai-Li , Wu Chao-Liang 
Published: April 2018

AbstractThe elongation of long-chain fatty acids family member 6 (Elovl6) is a key enzyme in lipogenesis that catalyzes the elongation of saturated and monounsaturated fatty acids. Insulin resistance involves upregulation of Elovl6, which has been linked to obesity-related malignancies, including hepatocellular carcinoma (HCC). However, the role of Elovl6 in cancer progression remains unknown. In this study, we analyzed the expression of Elovl6 in 61 clinical HCC specimens. Patients with Elovl6 high-expressing tumors were associated with shorter disease-free survival and overall survival compared to those with Elovl6 low-expressing tumors. Knockdown of Elovl6 in HCC cells reduced cell proliferation and Akt activation, as well as sensitivity to fatty acids. Inhibition of Elovl6 reduced tumor growth and prolonged survival in mice bearing tumors. Taken together, our results indicate that Elovl6 enhances oncogenic activity in liver cancer and is associated with poor prognosis in patients with HCC. Elovl6 may be a therapeutic target for HCC; thus, further studies to confirm this strategy are warranted.
Theoretical prediction and atomic kinetic Monte Carlo simulations of void superlattice self-organization under irradiation
Authors: Gao Yipeng , Zhang Yongfeng , Schwen Daniel , Jiang Chao , Sun Cheng , Gan Jian , Bai Xian-Ming 
Published: April 2018

AbstractNano-structured superlattices may have novel physical properties and irradiation is a powerful mean to drive their self-organization. However, the formation mechanism of superlattice under irradiation is still open for debate. Here we use atomic kinetic Monte Carlo simulations in conjunction with a theoretical analysis to understand and predict the self-organization of nano-void superlattices under irradiation, which have been observed in various types of materials for more than 40 years but yet to be well understood. The superlattice is found to be a result of spontaneous precipitation of voids from the matrix, a process similar to phase separation in regular solid solution, with the symmetry dictated by anisotropic materials properties such as one-dimensional interstitial atom diffusion. This discovery challenges the widely accepted empirical rule of the coherency between the superlattice and host matrix crystal lattice. The atomic scale perspective has enabled a new theoretical analysis to successfully predict the superlattice parameters, which are in good agreement with independent experiments. The theory developed in this work can provide guidelines for designing target experiments to tailor desired microstructure under irradiation. It may also be generalized for situations beyond irradiation, such as spontaneous phase separation with reaction.
Mutational profiling can identify laryngeal dysplasia at risk of progression to invasive carcinoma
Authors: Manterola Lorea , Aguirre Pablo , Larrea Erika , Arestín María , Gaafar Ayman , Elorriaga Kepa , Goicoechea Ibai , Armesto María , Fernández-Mercado Marta , Zabalza Ignacio , López-Duque Juan Carlos , Larruskain Ekhiñe , Sistiaga Jon Alexander , Landa Mikel , Zabala Aitor , Santaolalla Francisco , Municio José Antonio , Ispizua Ángel , García-Pedrero Juana María , Rodrigo Juan Pablo , Lawrie Charles Henderson 
Published: April 2018

AbstractEarly diagnosis of laryngeal squamous cell carcinoma (LSCC) at the stage of dysplasia could greatly improve the outcome of affected patients. For the first time we compared the mutational landscape of non-progressing dysplasia (NPD; n = 42) with progressing dysplasia (PD; n = 24), along with patient-matched LSCC biopsies; a total of 90 samples. Using targeted next-generation sequencing identified non-synonymous mutations in six genes (PIK3CA, FGFR3, TP53, JAK3, MET, FBXW7), and mutations were validated by Sanger sequencing and/or qPCR. Analysis was extended in silico to 530 head and neck (HNSCC) cases using TCGA data. Mutations in PIK3CA and FGFR3 were detected in PD and LSCC cases, as well as other HNSCC cases, but absent in NPD cases. In contrast, mutations in JAK3, MET and FBXW7 were found in NPD cases but not PD, LSCC or other HNSCC cases. TP53 was the most frequently mutated gene in both PD and NPD cases. With the exception of R248W, mutations were mutually exclusive. Moreover, five of seven PD mutations were located in motif H2 of p53, whereas none of the NPD mutations were. In summary, we propose that the mutational profile of laryngeal dysplasia has utility for the early detection of patients at risk of progression.
Prion protein modulates glucose homeostasis by altering intracellular iron
Authors: Ashok Ajay , Singh Neena 
Published: April 2018

AbstractThe prion protein (PrPC), a mainly neuronal protein, is known to modulate glucose homeostasis in mouse models. We explored the underlying mechanism in mouse models and the human pancreatic β-cell line 1.1B4. We report expression of PrPC on mouse pancreatic β-cells, where it promoted uptake of iron through divalent-metal-transporters. Accordingly, pancreatic iron stores in PrP knockout mice (PrP−/−) were significantly lower than wild type (PrP+/+) controls. Silencing of PrPC in 1.1B4 cells resulted in significant depletion of intracellular (IC) iron, and remarkably, upregulation of glucose transporter GLUT2 and insulin. Iron overloading, on the other hand, resulted in downregulation of GLUT2 and insulin in a PrPC-dependent manner. Similar observations were noted in the brain, liver, and neuroretina of iron overloaded PrP+/+ but not PrP−/− mice, indicating PrPC-mediated modulation of insulin and glucose homeostasis through iron. Peripheral challenge with glucose and insulin revealed blunting of the response in iron-overloaded PrP+/+ relative to PrP−/− mice, suggesting that PrPC-mediated modulation of IC iron influences both secretion and sensitivity of peripheral organs to insulin. These observations have implications for Alzheimer’s disease and diabetic retinopathy, known complications of type-2-diabetes associated with brain and ocular iron-dyshomeostasis.