bluuebunny/crossref_metadata_2025_split huggingface dataset:
The N Terminus of α‐Synuclein Forms CuII‐Bridged Oligomers
Authors: Drew Simon C. 
Published: March 2015

AbstractThe oligomerization of α‐synuclein (αSyn) is one of the defining features of Parkinson’s disease. Binding of divalent copper to the N terminus of αSyn has been implicated in both its function and dysfunction. Herein, the molecular details of the CuII/αSyn binding interface have been revealed using a library of synthetic 56‐residue αSyn peptides containing site‐specific isotopic labels. Using electron paramagnetic resonance spectroscopy, αSyn is shown to coordinate CuII with high affinity via two pH‐dependent coordination modes between pH 6.5–8.5. Most remarkably, the data demonstrate that the dominant mode is associated with binding to oligomers (antiparallel dimers and/or cyclic trimers) in which CuII ions occupy intermolecular bridging sites. The findings provide a molecular link between CuII‐bound αSyn and its associated quaternary oligomeric structure.
Fraktionsfreisetzungsgrad – Ein neuer Ansatz zur Quantifizierung der Staubungsneigung von Pulvern
Authors: Schmidt Eberhard 
Published: March 2015

AbstractDie prozessbedingte Beanspruchung von Feststoffen in disperser Form kann zur unerwünschten Freisetzung von Partikeln führen. Größe und Menge der in den Gasraum übergehenden Partikeln hängen von den haltenden und trennenden Kräften im Pulver ab, die wiederum durch charakteristische Größen des Pulvers und des Prozesses bestimmt werden. Analog zum Fraktionsabscheidegrad zur Beschreibung der Staubabscheidung wird hier der Fraktionsfreisetzungsgrad zur Quantifizierung der Staubfreisetzung eingeführt. Die Anwendung wird an einem Beispiel demonstriert und der Weg zur Weiterentwicklung dieses neuen Ansatzes aufgezeigt.
A distinct and replicable variant of the squamous cell carcinoma gene inositol polyphosphate‐5‐phosphatase modifies the susceptibility of arsenic‐associated skin lesions in Bangladesh
Authors: Seow Wei Jie , Pan Wen‐Chi , Kile Molly L. , Tong Lin , Baccarelli Andrea A. , Quamruzzaman Quazi , Rahman Mahmuder , Mostofa Golam , Rakibuz‐Zaman Muhammad , Kibriya Muhammad , Ahsan Habibul , Lin Xihong , Christiani David C. 
Published: March 2015

BACKGROUNDSingle‐nucleotide polymorphisms (SNPs) in inflammation, one‐carbon metabolism, and skin cancer genes might influence susceptibility to arsenic‐induced skin lesions.METHODSA case‐control study was conducted in Pabna, Bangladesh (2001‐2003), and the drinking‐water arsenic concentration was measured for each participant. A panel of 25 candidate SNPs was analyzed in 540 cases and 400 controls. Logistic regression was used to estimate the association between each SNP and the potential for gene‐environment interactions in the skin lesion risk, with adjustments for relevant covariates. Replication testing was conducted in an independent Bangladesh population with 488 cases and 2,794 controls.RESULTSIn the discovery population, genetic variants in the one‐carbon metabolism genes phosphatidylethanolamine N‐methyltransferase (rs2278952, P for interaction = .004; rs897453, P for interaction = .05) and dihydrofolate reductase (rs1650697, P for interaction = .02), the inflammation gene interleukin 10 (rs3024496, P for interaction = .04), and the skin cancer genes inositol polyphosphate‐5‐phosphatase (INPP5A; rs1133400, P for interaction = .03) and xeroderma pigmentosum complementation group C (rs2228000, P for interaction = .01) significantly modified the association between arsenic and skin lesions after adjustments for multiple comparisons. The significant gene‐environment interaction between a SNP in the INPP5A gene (rs1133400) and water arsenic with respect to the skin lesion risk was successfully replicated in an independent population (P for interaction = .03).CONCLUSIONSMinor allele carriers of the skin cancer gene INPP5A modified the odds of arsenic‐induced skin lesions in both main and replicative populations. Genetic variation in INPP5A appears to have a role in susceptibility to arsenic toxicity. Cancer 2015;121:2222–2229. © 2015 American Cancer Society.
Versatile Organic Transistors by Solution Processing
Authors: Ward Jeremy W. , Lamport Zachary A. , Jurchescu Oana D. 
Published: March 2015

AbstractA selection of the latest developments in organic electronic materials and organic field‐effect transistor (OFET) devices is reviewed here with an emphasis on the synthetic and manufacturing versatility, ease of processing, and low cost offered by solution processability. At the heart of these benefits is the nature of the weak van der Waals intermolecular interactions inherent to organic compounds. This allows processability with a relatively small amount of energy investment. Material solubility, in particular, creates unique pathways for film fabrication and the design of new device architectures, while presenting new manufacturing challenges to explore. In this review we provide a chronological presentation of the important developments in the solution‐deposited organic small‐molecule semiconductor, dielectric, and electrode materials used in OFETs, making specific note of current benchmarks. Organic device architectures and fabrication methods that are characterized by reduced complexity and ease of implementation are discussed.
Retention of nutrients, suspended particulate matter and phytoplankton in a pondage associated with a run‐of‐the‐river type hydroelectric power plant
Authors: Sow Mohamadou Mamoudou , Majdi Nabil , Muylaert Koenraad , Tackx Micky , Julien Frédéric , Probst Jean‐Luc , Mialet Benoît , Sutra Carine , Probst Anne , Thébault Jean‐Marc , Kenarlikdjian Mathilde , Gérino Magali 
Published: March 2015

AbstractReservoirs associated with run‐of‐the‐river type hydroelectrical power plants (i.e. pondages) have short water residence times. For this reason, pondages are thought to have a limited impact on the fluxes of particles and solutes transported by rivers. The Malause reservoir (South West France) is such a pondage. Fed by both the Garonne and Tarn rivers, it has a water residence time of only a few days. Incoming and outgoing fluxes of nutrients, suspended particulate matter (SPM) and phytoplankton were measured weekly over the course of 1 year. Mass balance calculations showed that Malause pondage retained 24% of soluble reactive phosphorus (SRP) supplied by both rivers on an annual basis. SRP retention occurred mostly in spring–summer, pointing to biological uptake. In addition, the pondage was a sink for SPM and phytoplankton, retaining 39% of SPM and 14% of chlorophyll a supplied by both rivers on an annual basis. The retention efficiency appeared to be constrained by water temperature and residence time. The pondage was a source of phytoplankton during summer, when temperature and water residence time was high. The pondage was a sink for SPM when water residence time was low (<1 day). Our observations highlight the need to reconsider the impact of minor hydrological discontinuities on the functioning of the river continuum. The shallow depth of the pondage and the presence of dense stands of submerged macrophytes have probably favoured the retention of nutrients and the sedimentation of particles within the pondage. Copyright © 2015 John Wiley & Sons, Ltd.
Permutation Testing in the Presence of Polygenic Variation
Authors: Abney Mark 
Published: March 2015

ABSTRACTThis article discusses problems with and solutions to performing valid permutation tests for quantitative trait loci in the presence of polygenic effects. Although permutation testing is a popular approach for determining statistical significance of a test statistic with an unknown distribution—for instance, the maximum of multiple correlated statistics or some omnibus test statistic for a gene, gene‐set, or pathway—naive application of permutations may result in an invalid test. The risk of performing an invalid permutation test is particularly acute in complex trait mapping where polygenicity may combine with a structured population resulting from the presence of families, cryptic relatedness, admixture, or population stratification. I give both analytical derivations and a conceptual understanding of why typical permutation procedures fail and suggest an alternative permutation‐based algorithm, MVNpermute, that succeeds. In particular, I examine the case where a linear mixed model is used to analyze a quantitative trait and show that both phenotype and genotype permutations may result in an invalid permutation test. I provide a formula that predicts the amount of inflation of the type 1 error rate depending on the degree of misspecification of the covariance structure of the polygenic effect and the heritability of the trait. I validate this formula by doing simulations, showing that the permutation distribution matches the theoretical expectation, and that my suggested permutation‐based test obtains the correct null distribution. Finally, I discuss situations where naive permutations of the phenotype or genotype are valid and the applicability of the results to other test statistics.
Differential relations between juvenile psychopathic traits and resting state network connectivity
Authors: Cohn Moran D. , Pape Louise E. , Schmaal Lianne , van den Brink Wim , van Wingen Guido , Vermeiren Robert R.J.M. , Doreleijers Theo A.H. , Veltman Dick J. , Popma Arne 
Published: March 2015

AbstractTraditionally, neurobiological research on psychopathy has focused on categorical differences in adults. However, there is evidence that psychopathy is best described by a set of relatively independent personality dimensions, that is, callous‐unemotional, grandiose‐manipulative, and impulsive‐irresponsible traits, which can be reliably detected in juveniles, allowing investigation of the neural mechanisms leading to psychopathy. Furthermore, complex psychiatric disorders like psychopathy are increasingly being conceptualized as disorders of brain networks. The intrinsic organization of the brain in such networks is reflected by coherent fluctuations in resting state networks (RSNs), but these have not been studied in sufficient detail in relation to juvenile psychopathic traits yet. The current study investigated the distinct associations of juvenile psychopathic traits dimensions with RSN connectivity. Resting‐state functional MRI and independent component analysis were used to assess RSN connectivity in a large sample of adolescents (n = 130, mean age 17.8 years) from a childhood arrestee cohort. Associations between scores on each of the three psychopathic traits dimensions and connectivity within and between relevant RSNs were investigated. Callous‐unemotional traits were related to aberrant connectivity patterns of the default mode network, which has been implicated in self‐referential and moral processes. Impulsive‐irresponsible traits were associated with altered connectivity patterns in the frontoparietal cognitive control networks. Grandiose‐manipulative traits were not associated with altered connectivity patterns. These findings confirm the association between psychopathic traits and brain network connectivity, and considerably add to emerging evidence supporting neurobiological heterogeneity in the processes leading to psychopathy. Hum Brain Mapp 36:2396–2405, 2015. © 2015 Wiley Periodicals, Inc.
Impacts of model initialization on an integrated surface water–groundwater model
Authors: Ajami Hoori , McCabe Matthew F. , Evans Jason P. 
Published: March 2015

AbstractIntegrated hydrologic models characterize catchment responses by coupling the subsurface flow with land surface processes. One of the major areas of uncertainty in such models is the specification of the initial condition and its influence on subsequent simulations. A key challenge in model initialization is that it requires spatially distributed information on model states, groundwater levels and soil moisture, even when such data are not routinely available. Here, the impact of uncertainty in initial condition was explored across a 208 km2 catchment in Denmark using the ParFlow.CLM model. The initialization impact was assessed under two meteorological conditions (wet vs dry) using five depth to water table and soil moisture distributions obtained from various equilibrium states (thermal, root zone, discharge, saturated and unsaturated zone equilibrium) during the model spin‐up. Each of these equilibrium states correspond to varying computation times to achieve stability in a particular aspect of the system state.Results identified particular sensitivity in modelled recharge and stream flow to the different initializations, but reduced sensitivity in modelled energy fluxes. Analysis also suggests that to simulate a year that is wetter than the spin‐up period, an initialization based on discharge equilibrium is adequate to capture the direction and magnitude of surface water–groundwater exchanges. For a drier or hydrologically similar year to the spin‐up period, an initialization based on groundwater equilibrium is required. Variability of monthly subsurface storage changes and discharge bias at the scale of a hydrological event show that the initialization impacts do not diminish as the simulations progress, highlighting the importance of robust and accurate initialization in capturing surface water–groundwater dynamics. Copyright © 2015 John Wiley & Sons, Ltd.
Going Public
Authors: Lammers Jayne C. , Marsh Valerie L. 
Published: March 2015

AbstractBuilding upon research exploring adolescent writing in technology‐mediated contexts, this article examines writing and sharing in the online space of Fanfiction.net. Drawing on qualitative data from a longitudinal inquiry with a 16‐year‐old who writes in multiple contexts, this study explores the writing opportunities afforded on Fanfiction.net and how the fanfiction public shapes one adolescent's practices and perspectives as a writer. Grounded in a view of literacies as social practices and contemporary theories of audience and networked publics, this instrumental case study presents the particularity and complexity of writing within the Fanfiction.net public. Findings reveal how fanfiction's access, anonymity, and conventions create a multifaceted experience of writing for and sharing with audience in ways unavailable to this adolescent in school. The article conceptualizes networked writing and offers recommendations to foster classroom writing with a similar emphasis on audiences.
Extreme daily precipitation events at Spitsbergen, an Arctic Island
Authors: Serreze Mark C. , Crawford Alex D. , Barrett Andrew P. 
Published: March 2015

ABSTRACTDaily station records and output from the MERRA atmospheric reanalysis for the period 1979 onwards are used to examine extreme daily precipitation events at Ny Ålesund and three other sites located on Spitsbergen. Spitsbergen, lying between 77°N and 80°N, is the largest island of the Svalbard Archipelago. The region is frequently influenced by extratropical cyclones associated with the North Atlantic cyclone track and (in winter) regional baroclinicity due to proximity to the sea ice margin. Despite the stronger cyclone activity in winter, extreme precipitation events at Ny Ålesund, defined as those in the top 1% of the statistical distribution, can occur year round. On the basis of a composite analysis, extreme events tend to occur when the region is influenced by a trough of low sea level pressure extending from the southwest, southerly winds in the troposphere, positive anomalies in precipitable water, and pronounced upward motion (negative omega) at 500 hPa. This is linked to positive anomalies in 500 hPa heights over the Barents Sea and negative anomalies over Greenland. While individual extreme events do not share all of these characteristics, strong southerly flow and positive anomalies in precipitable water provide a near common thread. Reflecting local topography, extremes at Ny Ålesund are typically not well represented at other stations on the island, but there are notable exceptions. Some of the largest precipitation events can be associated with features resembling ‘atmospheric rivers’, seen as narrow corridors of pronounced positive anomalies in precipitable water extending thousands of kilometres south into the subtropical Atlantic. There is no systematic pattern of temporal trends in the frequency or magnitude of extremes.
Tranexamic acid precipitating onset of acute myocardial infarction
Authors: Ngo‐Thai Lam Lan , Gellatly Rochelle , Nanayakkara Shane 
Published: March 2015

AbstractBackgroundTranexamic acid is an antifibrinolytic agent used to reduce bleeding in surgeries with high postoperative bleeding risk and conditions such as menorrhagia. Due to increased risk of thrombosis it is contraindicated in patients with past history of venous thrombosis. What is less clear is the association of tranexamic acid with arterial thrombosis such as acute myocardial infarction. To date, there are five published case reports describing this association in patients with pre‐existing cardiovascular risk factors.AimTo increase awareness of the association between tranexamic acid and acute myocardial infarction.Clinical detailsA 41‐year‐old female presented with non‐ST elevation myocardial infarction 7 days post a course of oral tranexamic acid 1 g three times a day taken on day 1 of menses until completion of menses. She had no known cardiovascular risk factors.OutcomeThe angiogram revealed a 70% stenosis within the proximal and mid segment of the first diagonal of the left anterior descending artery (LADD1). The presence of a 70% stenosis suggests pre‐existing disease prior to tranexamic acid use, complicated by thrombus formation leading to the non‐ST elevation myocardial infarction. The lesion was stented with a drug eluting stent and the patient was commenced on aspirin, ticagrelor, metoprolol and atorvastatin. Future use of tranexamic acid was discouraged and a levonorgestrol intrauterine device was suggested as an alternative treatment for menorrhagia.ConclusionThis case adds to existing literature that tranexamic acid may precipitate the onset of acute myocardial infarction and this should be considered especially when it is prescribed in patients with cardiovascular risk factors.
Results of a clinical audit on drug‐related problems identified by a clinical pharmacist in a thoracic outpatient clinic
Authors: Canning Martin L. , Masel Philip , Tse Tracy 
Published: March 2015

AbstractAimTo identify the types and severity of drug‐related problems (DRPs) identified by a pharmacist in a thoracic outpatient clinic.MethodsA clinical pharmacist reviewed patients in a thoracic outpatient clinic weekly for 17 weeks where medication history interview and pharmaceutical review were undertaken on available patients. DRPs identified were communicated to the treating respiratory physician or registrar and patient. DRPs were reviewed retrospectively by an independent specialist thoracic pharmacist and a consultant thoracic physician. The DRPs were classified according to the Pharmaceutical Care Network Europe Classification V 6.2 and whether respiratory or non‐respiratory related.ResultsA total of 97 DRPs were identified in 66 patients reviewed; an average of 1.47 DRPs per patient; 50 were non‐respiratory related and 47 respiratory related. The most common DRP was ‘effect of drug treatment not optimal’ (n = 35, 36%) followed by ‘non‐allergic adverse drug event’ (n = 23, 23.7%) and ‘untreated indication’ (n = 23, 23.7%). The most common pharmaceutical intervention performed was ‘patient (medication) counselling’. A total of 37% (n = 36) DRPs were deemed to be high or extremely high risk by an independent pharmacist and 44% (n = 43) high risk by a consultant thoracic physician.ConclusionThere is a potential role for pharmacists in a specialist thoracic outpatient clinic as pharmacist attendance allowed respiratory and non‐respiratory DRPs to be identified and interventions proposed. A large number of DRPs were deemed to be high or extremely high risk. Pharmacist attendance also provides an opportunity for patient education and counselling.
Prevalence of swallowing difficulties and medication modification in customers of community pharmacists
Authors: Lau Esther T. L. , Steadman Kathryn J. , Mak Marilyn , Cichero Julie A. Y. , Nissen Lisa M. 
Published: March 2015

AbstractBackgroundPeople may alter their solid oral medication dosage forms to make it easier to swallow. However, modification of solid medication dosage forms can lead to adverse effects, and people may alter the dosage forms without informing the health professionals involved in their care.AimTo estimate the prevalence of swallowing difficulties and medication dosage form modification among community pharmacy consumers, and to investigate consumer views, attitudes and interactions with health professionals regarding such issues.MethodConsumers were recruited from five community pharmacies in Brisbane, Australia and invited to participate in a structured interview.ResultsA total of 369 consumers participated in the study. Overall, 16.5% of people reported experiencing swallowing difficulties, and 10.6% of all respondents reported modifying medication dosage forms. Almost half (44.2%) of those surveyed did not think there would be issues with modifying medication dosage forms. Some consumers would not seek advice from health professionals if they experienced swallowing problems and/or would not seek advice from health professionals before modifying their medication dosage forms, regardless of their thoughts about any problems associated with this practice.ConclusionSome consumers appeared to be accustomed to modifying medication dosage forms, even when there was no apparent or obvious need. People were also reluctant to seek advice from health professionals regarding swallowing difficulties, or modifying medication dosage forms. Health professionals must be assertive in educating consumers about swallowing problems, and medication dosage form modification.
Managing vaccine‐associated anaphylaxis in the pharmacy
Authors: Bushell Mary‐Jessimine A. , Ball Patrick A. 
Published: March 2015

AbstractBackgroundAlthough vaccine‐associated anaphylaxis is very rare, it is the most serious of adverse events. An emerging role for appropriately credentialed pharmacists in Australia is the administration of vaccines to adults. Pharmacists administering vaccinations must be adequately prepared and competent to act should anaphylaxis occur within the community pharmacy setting.AimThis paper aims to review the evidence, identifies recommendations for established vaccinators administering vaccines in the community setting and provides recommendations for the most appropriate management of anaphylaxis in the community pharmacy setting.DiscussionAvailable literature revealed that the pharmacist vaccinator should utilise a pre‐vaccination checklist to screen for patients at high risk of anaphylaxis. All pharmacists administering vaccines should demonstrate assessed competency using both available brands of adrenaline auto‐injectors and demonstrate the adrenaline ampoule/needle/syringe technique. There is a strong case for pharmacist anaphylaxis response kits to contain at minimum three in‐date adult adrenaline auto‐injectors, in addition to other components of the kit. Pharmacies providing a vaccination service must have an appropriate treatment room and display a posted, written emergency protocol. Pharmacists should be able to identify anaphylaxis and differentiate this medical emergency from other adverse events following immunisation such as vasovagal syncope.ConclusionTo ensure public health, pharmacists administering vaccines must be prepared for, able to screen for and immediately recognise and manage vaccine‐associated anaphylaxis and ensure appropriate follow‐up and referral.