bluuebunny/crossref_metadata_2025_split huggingface dataset:
Family‐Based Rare Variant Association Analysis: A Fast and Efficient Method of Multivariate Phenotype Association Analysis
Authors: Wang Longfei , Lee Sungyoung , Gim Jungsoo , Qiao Dandi , Cho Michael , Elston Robert C , Silverman Edwin K , Won Sungho 
Published: June 2016

AbstractFamily‐based designs have been repeatedly shown to be powerful in detecting the significant rare variants associated with human diseases. Furthermore, human diseases are often defined by the outcomes of multiple phenotypes, and thus we expect multivariate family‐based analyses may be very efficient in detecting associations with rare variants. However, few statistical methods implementing this strategy have been developed for family‐based designs. In this report, we describe one such implementation: the multivariate family‐based rare variant association tool (mFARVAT). mFARVAT is a quasi‐likelihood‐based score test for rare variant association analysis with multiple phenotypes, and tests both homogeneous and heterogeneous effects of each variant on multiple phenotypes. Simulation results show that the proposed method is generally robust and efficient for various disease models, and we identify some promising candidate genes associated with chronic obstructive pulmonary disease. The software of mFARVAT is freely available at http://healthstat.snu.ac.kr/software/mfarvat/, implemented in C++ and supported on Linux and MS Windows.
Exposure Enriched Case‐Control (EECC) Design for the Assessment of Gene–Environment Interaction
Authors: Huque Md Hamidul , Carroll Raymond J. , Diao Nancy , Christiani David C. , Ryan Louise M. 
Published: June 2016

ABSTRACTGenetic susceptibility and environmental exposure both play an important role in the aetiology of many diseases. Case‐control studies are often the first choice to explore the joint influence of genetic and environmental factors on the risk of developing a rare disease. In practice, however, such studies may have limited power, especially when susceptibility genes are rare and exposure distributions are highly skewed. We propose a variant of the classical case‐control study, the exposure enriched case‐control (EECC) design, where not only cases, but also high (or low) exposed individuals are oversampled, depending on the skewness of the exposure distribution. Of course, a traditional logistic regression model is no longer valid and results in biased parameter estimation. We show that addition of a simple covariate to the regression model removes this bias and yields reliable estimates of main and interaction effects of interest. We also discuss optimal design, showing that judicious oversampling of high/low exposed individuals can boost study power considerably. We illustrate our results using data from a study involving arsenic exposure and detoxification genes in Bangladesh.
Sequential patterns in Cenozoic marginal basins of the Northwest Pacific
Authors: Xu Shumei , Ye Qing , Li Sanzhong , Somerville Ian , Feng Huaiwei , Tang Ziwen , Shu Dongge , Bi Haiming 
Published: June 2016

AbstractBy using magnetic anomaly identifications, onshore and offshore exploratory wells, ODP drillings, isotopic dating and orthochronology results, this paper summarizes the tectonic event sequence (including extension, back‐arc spreading, subsidence, convergence/compressive deformation and thrusting) of the marginal basins of the NW Pacific and extracted sequence patterns of the marginal basins according to the tectonic event sequence from an array of oil company regional seismic lines and other geological data. Three important evolutionary stages of the Northwestern Pacific (NW Pacific) marginal sea basins are distinguished: from the Palaeocene to Eocene, from Oligocene to Middle Miocene and from the later Middle Miocene to the present day. Each stage corresponds to a rifting sequence (Palaeocene to Eocene), a drifting sequence (Oligocene to Middle Miocene) and a subsidence/convergence sequence (later Middle Miocene to the present day). The rifting sequence and drifting sequence developed sequentially in the South China Sea Basin, from Palaeocene to Eocene and from Oligocene to Middle Miocene, while in the Japan and Okhotsk Sea basins, an early stage rifting sequence was not developed in the Palaeocene to Eocene interval. However, the drifting and rifting sequence developed synchronously from the Oligocene to Middle Miocene. From the Later Miocene time, all the marginal basins of the Northwest Pacific basically stopped drifting and began to enter the subsidence (post‐drifting) stage. An arc‐continent collision from the south caused the formation of a convergence sequence in the southern margin of each marginal basin. The NW Pacific Plate collision with the Kuril–Kamchatka Arc led to the deformation of the subsidence sequence in the southern margin of the Kuril Sea Basin. The NW Pacific Plate convergence with the Japan Arc led to the formation of a convergence sequence in the southern margin of the Japan Sea Basin. The Borneo–Palawan Arc convergence with the Dangerous Grounds–Reed Bank Block in the South China Sea Basin from 15 Ma led to the formation of the convergence sequence in the southern margin of the South China Sea Basin. The degree of thrusting deformation of the convergent sequence increased gradually from north to south in the marginal basins of the Northwest Pacific. Copyright © 2016 John Wiley & Sons, Ltd.
Can Physicians Affect Patient Adherence With Medication?
Authors: Koulayev Sergei , Simeonova Emilia , Skipper Niels 
Published: June 2016

AbstractNon‐compliance with medication therapy remains an unsolved and expensive problem for healthcare systems around the world, yet we know little about the factors that affect a patient's decision to follow treatment recommendations. In particular, there is little evidence on the extent to which doctors can influence patient adherence behavior. This study uses a unique panel dataset comprising all prescription drug users, physicians, and all prescription drug sales in Denmark over 7 years to analyze the contributions of doctor‐specific, patient‐specific, and drug‐specific factors to the adherence decision. We find that physicians exert substantial influence on patient compliance. Further, the quality of the match between a doctor and a patient accounts for a substantial portion of the variation in adherence outcomes. This suggests that the sorting of patients across doctors is an important mechanism that affects patient adherence beyond the effects of individual patient‐specific and physician‐specific factors. Copyright © 2016 John Wiley & Sons, Ltd.
A model of topological mapping of space in bat hippocampus
Authors: Hoffman Kentaro , Babichev Andrey , Dabaghian Yuri 
Published: June 2016

ABSTRACTThe mammalian hippocampus plays a key role in spatial learning and memory, but the exact nature of the hippocampal representation of space is still being explored. Recently, there has been a fair amount of success in modeling hippocampal spatial maps in rats, assuming a topological perspective on spatial information processing. In this article, we use the topological approach to study the formation of a 3D spatial map in bats, which produces several insights into neurophysiological mechanisms of the hippocampal spatial leaning. First, we demonstrate that, in order to produce accurate maps of the environment, place cell should be organized into functional groups, which can be interpreted as cell assemblies. Second, the model suggests that the readout neurons in these cell assemblies should function as integrators of synaptic inputs, rather than detectors of place cells' coactivity, which allows estimating the integration time window. Lastly, the model suggests that, in contrast with relatively slow moving rats, suppressing θ‐precession in bats improves the place cells capacity to encode spatial maps, which is consistent with the experimental observations. © 2016 Wiley Periodicals, Inc.
Optimal Dose of Calcium for Treatment of Nutritional Rickets: A Randomized Controlled Trial
Authors: Thacher Tom D , Smith Lauren , Fischer Philip R , Isichei Christian O , Cha Stephen S , Pettifor John M 
Published: June 2016

ABSTRACT

Calcium supplementation is indicated for the treatment of nutritional rickets. Our aim was to determine the optimal dose of calcium for treatment of children with rickets. Sixty-five Nigerian children with radiographically confirmed rickets were randomized to daily supplemental calcium intake of 500 mg (n = 21), 1000 mg (n = 23), or 2000 mg (n = 21). Venous blood, radiographs, and forearm areal bone density (aBMD) were obtained at baseline and at 8, 16, and 24 weeks after enrollment. The primary outcome was radiographic healing, using a 10-point radiographic severity score. The radiographic severity scores improved in all three groups, but the rate of radiographic healing (points per month) was significantly more rapid in the 1000-mg (–0.29; 95% confidence interval [CI] –0.13 to –0.45) and 2000-mg (–0.36; 95% CI –0.19 to –0.53) supplementation groups relative to the 500-mg group. The 2000-mg group did not heal more rapidly than the 1000-mg group. Of those who completed treatment for 24 weeks, 12 (67%), 20 (87%), and 14 (67%) in the 2000-mg, 1000-mg, and 500-mg groups, respectively, had achieved a radiographic score of 1.5 or less (p = 0.21). Serum alkaline phosphatase decreased and calcium increased similarly in all groups. Forearm diaphyseal aBMD improved significantly more rapidly in the 2000-mg group than in the 500-mg and 1000-mg groups (p &lt; 0.001). Daily calcium intakes of 1000 mg or 2000 mg produced more rapid radiographic healing of rickets than 500 mg, but 2000 mg did not have greater benefit than 1000 mg. Some children require longer than 24 weeks for complete healing of nutritional rickets. © 2016 American Society for Bone and Mineral Research.
The Monochromatic Circumference of 2‐Edge‐Colored Graphs
Authors: White Matthew 
Published: June 2016

AbstractLi et al. (Discrete Math 310 (2010), 3579–3583) asked how long the longest monochromatic cycle in a 2‐edge‐colored graph G with minimum degree at least could be. In this article, an answer is given for all to an asymptotic form of their question.
Tips and tricks of laparoscopic distal pancreatectomy for ductal adenocarcinoma
Authors: Kooby David A. 
Published: June 2016

AbstractLaparoscopic distal pancreatectomy for pancreatic cancer can be a challenging procedure that requires adherence to surgical principles respecting tissue planes and critical vascular structures to obtain the optimal surgical margins and peripancreatic node harvest, while minimizing damage to surrounding structures. This report provides a basic approach with some tips and tricks based on my experience with this procedure.
Extreme weather events over China: assessment of COSMO‐CLM simulations and future scenarios
Authors: Bucchignani Edoardo , Zollo Alessandra Lucia , Cattaneo Luigi , Montesarchio Myriam , Mercogliano Paola 
Published: June 2016

ABSTRACTExtreme climate events over a wide Chinese area are investigated with the regional climate model COSMO‐CLM at high resolution (0.125°) through the use of some extreme indicators. Two hindcast simulations, driven respectively by ERA‐Interim reanalysis and the global model CMCC‐CM over the period 1979–2011 have been analysed in order to check the model's ability to represent a subset of climate indicators for precipitation and temperature, as a preliminary step to assess changes regarding extreme weather events expected under greenhouse gas concentration variations. The effort to increase resolution in a regional model has interesting benefits in representing extreme indices, especially in complex orography areas. Results show that the model provides a good representation of the spatial climatology of the indices considered, with high correlation values between the model and observations. Future climate changes concerning extreme events have been investigated, employing the IPCC RCP4.5 and RCP8.5 scenarios. Projections reveal that temperature indicators are characterized by positive trend values, highlighting an increase in minimum and maximum temperatures over the period 2041–2070, especially over southeast China. Extreme precipitation events are generally projected to increase over the whole region considered, especially under RCP8.5 scenario.
CK2.1, a novel peptide, induces articular cartilage formation in vivo
Authors: Akkiraju Hemanth , Bonor Jeremy , Nohe Anja 
Published: June 2016

ABSTRACTBone morphogenetic protein 2 regulates chondrogenesis and cartilage formation. However, it also induces chondrocyte hypertrophy and cartilage matrix degradation. We recently designed three peptides CK2.1, CK2.2, and CK2.3 that activate the BMP signaling pathways by releasing casein kinase II (CK2) from distinct sites at the bone morphogenetic protein receptor type Ia (BMPRIa). Since BMP2 is a major regulator of chondrogenesis and the peptides activated BMP signaling in a similar way, we evaluated the effect of these peptides on chondrogenesis and cartilage formation. C3H10T1/2 cells were stimulated with CK2.1, CK2.2, and CK2.3 and evaluated for the chondrogenic and osteogenic potential. For chondrogenesis, Alcian blue staining was performed. Additionally, collagen types II and X expression was measured. For osteogenesis, osteocalcin and von Kossa staining were performed. From the three peptides, CK2.1 was the most promising peptide to induce chondrogenesis but not osteogenesis. To investigate the effect of CK2.1 on articular cartilage formation in vivo, we injected CK2.1 into the tail vein of mice. Injection of CK2.1 into the tail vein of mice led to increased articular cartilage formation but not BMD. In sharp contrast, injection of BMP2 led to increased BMD and expression of collagen type X, a marker of chondrocyte hypertrophy. MMP13 expression was unchanged. Our study demonstrates that CK2.1 drives chondrogenesis and cartilage formation without induction of chondrocyte hypertrophy. Peptide CK2.1 may, therefore, be a valuable therapeutic for cartilage degenerative diseases. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:876–885, 2017.
Interpretation and application of carbon isotope ratios in freshwater diatom silica
Authors: Webb Megan , Barker Philip A. , Wynn Peter M. , Heiri Oliver , van Hardenbroek Maarten , Pick Frances , Russell James M. , Stott Andy W. , Leng Melanie J. 
Published: June 2016

ABSTRACTCarbon incorporated into diatom frustule walls is protected from degradation enabling analysis for carbon isotope composition (δ13Cdiatom). This presents potential for tracing carbon cycles via a single photosynthetic host with well‐constrained ecophysiology. Improved understanding of environmental processes controlling carbon delivery and assimilation is essential to interpret changes in freshwater δ13Cdiatom. Here relationships between water chemistry and δ13Cdiatom from contemporary regional data sets are investigated. Modern diatom and water samples were collected from river catchments within England and lake sediments from across Europe. The data suggest dissolved, biogenically produced carbon supplied proportionately to catchment productivity was critical in the rivers and soft water lakes. However, dissolved carbon from calcareous geology overwhelmed the carbon signature in hard water catchments. Both results demonstrate carbon source characteristics were the most important control on δ13Cdiatom, with a greater impact than productivity. Application of these principles was made to a sediment record from Lake Tanganyika. δ13Cdiatom co‐varied with δ13Cbulk through the last glacial and Holocene. This suggests carbon supply was again dominant and exceeded authigenic demand. This first systematic evaluation of contemporary δ13Cdiatom controls demonstrates that diatoms have the potential to supply a record of carbon cycling through lake catchments from sediment records over millennial timescales.
Mass accumulation rate and monsoon records from Xifeng, Chinese Loess Plateau, based on a luminescence age model
Authors: Stevens Thomas , Buylaert Jan‐Pieter , Lu Huayu , Thiel Christine , Murray Andrew , Frechen Manfred , Yi Shuangwen , Zeng Lin 
Published: June 2016

ABSTRACTLuminescence dating of loess accumulation in China has raised questions over disturbance and gaps in the record, the magnitude of mass accumulation rates (MARs), and monsoon forcing mechanisms. Here we present a detailed quartz optically stimulated luminescence (OSL) chronology from the Xifeng Chinese Loess Plateau site. We reconstruct MARs and construct an age model for monsoon proxies at the site. The luminescence ages show significant pedogenic and anthropogenic disturbance in material deposited after ca. 20–22 ka. Analysis of other published data suggests that this disturbance may be more common than previously realized. MARs from undisturbed portions of Xifeng vary dramatically, with peaks potentially matching the timing of Heinrich events. The last glacial maximum peak MAR (22–27 ka) matches the Pacific and Greenland dust flux records, although appears earlier than peak MARs seen in many other OSL‐dated Loess Plateau sites. East Asian monsoon grain‐size and magnetic susceptibility records also show several differences between independently dated loess sites. This complicates our understanding of any lag between insolation forcing and monsoon response. Nevertheless, the Xifeng climate proxy changes show apparent broad agreement with the timing of Heinrich events in the North Atlantic, supporting assertions of a climatic teleconnection between the two areas.
Caution in cryptotephra correlation: resolving Lateglacial chemical controversies at Sluggan Bog, Northern Ireland
Authors: MacLeod A. , Davies S. M. 
Published: June 2016

ABSTRACTTephra layers are valuable stratigraphic and chronological markers in palaeoenviromental studies. Establishing robust linkages requires complete comparative databases of eruptive events to ensure that potential correlatives are not overlooked. This is achieved through the construction of tephrostratigraphical inventories from exposures proximal to the volcanic source. Proximally characterized ash layers are frequently detected thousands of kilometres from source alongside a limited number of tephras with no apparent proximal correlative. Despite the inability to correlate with a specific eruption, source volcanoes can be proposed and many of these far‐field occurrences have become well‐established stratigraphic markers. However, careful scrutiny is essential to verify the primary and instantaneous fallout origin of these distant occurrences. Here we present new data which provide an explanation for the long‐standing controversy surrounding the source of Lateglacial age cryptotephras within Sluggan Bog, Northern Ireland. Chemical analysis of glass shards detected within this sequence suggests they originate from an obsidian exposure located 11 km from the site, rather than from a contemporaneous eruptive event. This discovery highlights the importance of giving appropriate consideration to the enclosing geology of a particular palaeorecord. We suggest locations where geological sources might complicate air‐fall records of tephra deposition and propose a means by which to address this challenge.
Anthropogenic forcing increases the water‐use efficiency of African trees
Authors: Wils Tommy H. G. , Robertson Iain , Woodborne Stephan , Hall Grant , Koprowski Marcin , Eshetu Zewdu 
Published: June 2016

ABSTRACTRising atmospheric CO2 concentrations affect climate directly through radiative effects and indirectly by changing plant water‐use efficiency. Under global warming scenarios these widely reported changes will have a substantial impact on future bush encroachment, crop yields, river flow and climate feedbacks. Tree‐ring intrinsic water‐use efficiency (iWUE) records for Africa show a 24.6% increase over the 20th century. As high iWUE can partly counterbalance projected decreases in regional precipitation, this research has important implications for those involved in water resource management and highlights the need for climate models to take physiological forcing into account.
The 8.2‐ka BP event in north‐eastern North America: first combined oxygen and hydrogen isotopic data from peat in Newfoundland
Authors: Daley T. J. , Barber K. E. , Hughes P. D. M. , Loader N. J. , Leuenberger M. , Street‐Perrott F. A. 
Published: June 2016

ABSTRACTFinding direct evidence for atmospheric circulation change in terrestrial records of Holocene climate variability remains a fundamental challenge. Here we present the first combined stable oxygen and hydrogen isotopic palaeorecord from a peatland core in Newfoundland, Canada. Sphagnum cellulose samples were isolated from a core from Nordan's Pond Bog, Newfoundland, and analysed for δD values. Combined with existing δ18O data, the resulting δD/δ18O bi‐plot correlates directly with existing measurements of the modern (late 20th century) isotopic composition of precipitation from GNIP stations in Nova Scotia and Labrador, implying a close relationship between the estimated isotopic composition of source water used by the mosses and that of the source precipitation. We use the relative variations between the two isotope records to test the hypothesis that atmospheric circulation changed in the millennium following the 8.2‐ka BP climate event. The data reveal a secondary complex isotopic response ∼200 years (8250–8050 a BP) after a primary oxygen isotopic event that is widespread in the north Atlantic region. This secondary event is characterized by a divergence in oxygen and hydrogen isotope records that can most plausibly be explained by the augmentation of precipitation moisture from a more distant and more continental vapour source.
Effects of toxic cyanobacteria and ammonia on flesh quality of blunt snout bream (Megalobrama amblycephala)
Authors: Wang Li , Chen Chuanyue , Liu Wanjing , Xia Hu , Li Jian , Zhang Xuezhen 
Published: June 2016

AbstractBACKGROUNDToxic cyanobacterial blooms result in the production of an organic biomass containing cyanotoxins (e.g. microcystins) and an elevated ammonia concentration in the water environment. The ingestion of toxic cyanobacteria and exposure to ammonia are grave hazards for fish. The present study assessed the effects of dietary toxic cyanobacteria and ammonia exposure on the flesh quality of blunt snout bream (Megalobrama amblycephala).RESULTSDietary toxic cyanobacteria and ammonia exposure had no impact on fish growth performance, fillet proximate composition and drip loss, whereas it significantly decreased fillet total amino acids, total essential amino acids, hardness and gumminess, and increased fillet ultimate pH as well as malondialdehyde content. However, there was no significant interaction between dietary toxic cyanobacteria and ammonia exposure on these parameters. Additionally, dietary toxic cyanobacteria significantly increased fillet initial pH, thaw loss and protein carbonyl content, whereas ammonia exposure did not.CONCLUSIONThe results of the present study indicate that dietary toxic cyanobacteria and ammonia exposure reduced the quality of blunt snout bream fillet. © 2016 Society of Chemical Industry