bluuebunny/crossref_metadata_2025 huggingface dataset:
Complex renal cysts associated with crizotinib treatment
Authors: Schnell Patrick , Bartlett Cynthia H. , Solomon Benjamin J. , Tassell Vanessa , Shaw Alice T. , de Pas Tommaso , Lee Soo‐Hyun , Lee Geon Kook , Tanaka Kaoru , Tan Weiwei , Tang Yiyun , Wilner Keith D. , Safferman Allan , Han Ji‐Youn
Published: March 2015

An apparent causal association between crizotinib treatment and renal cyst development emerged during clinical trials in anaplastic lymphoma kinase (ALK)‐positive non–small cell lung cancer (NSCLC). Serious adverse event (SAE) reports of renal cysts from a safety database of 1375 patients from four clinical trials were reviewed. A blinded, retrospective, independent radiologic review (IRR) was performed using scans from patients on study for ≥6 months in three clinical trials; risk factors for renal cyst development were assessed. Among 17 patients with renal cysts reported as SAEs, evidence of invasion into adjacent structures was noted in seven patients, with no evidence of malignancy found. These patients generally did not require dose reductions, none required permanent crizotinib discontinuation due to this AE, and most continued treatment with clinical benefit. In the blinded IRR, among 255 crizotinib‐treated patients, 22%, 3%, and 2% had preexisting simple cysts, complex cysts, or both, respectively. At the 6‐month tumor assessment, 9% of all patients had acquired new cysts, and 2% of patients with preexisting cysts had developed new cysts and enlargements (>50%) of preexisting simple cysts. Asians appeared to have an increased risk of developing new cysts on treatment; Koreans in particular had 5.18 times higher odds of developing cysts than non‐Asians (95% confidence interval, 1.51–17.78; P = 0.05). Crizotinib treatment appears to be associated with an increased risk of development and progression of renal cysts in patients with ALK‐positive NSCLC. While close monitoring is recommended, dosing modification was not generally necessary, allowing patients to remain on crizotinib treatment.
Do your policies make the grade for handling large‐scale academic misconduct?
Authors: Porter Michael
Published: March 2015

Recent and ongoing academic misconduct investigations at dozens of colleges and universities serve as sobering reminders of the challenges of dealing with issues concerning academic integrity.
Achieve greater career success with strategic planning
Authors: Santovec Mary Lou
Published: March 2015

While success does sometimes happen purely by accident, there are ways to intentionally design it.
Refractory immune thrombocytopenia. Successful treatment with repeated cyclosporine A: two case reports
Authors: Hlusi Antonin , Szotkowski Tomas , Indrak Karel
Published: March 2015

Key Clinical Message

Treatment of chronic, severe refractory immune thrombocytopenia after splenectomy is difficult. Only less data exist on clinical use of cyclosporine A (CyA) in the management of refractory ITP. In this report, we describe two cases in which standard immunosuppressive therapy, other immunosuppression including cyclosporine A or splenectomy had no therapeutic effect. Even after splenectomy, recommended procedures were inefficient and critical thrombocytes count persisted. After repeated administration of cyclosporine A which had been ineffective prior to splenectomy; however, both patients achieved long‐term complete remission of the ITP. Side effects of CyA were moderate. The presented cases have confirmed the potential therapeutic effect of CyA in refractory post‐SE ITP.
Iridium‐Catalyzed Sustainable Access to Functionalized Julolidines through Hydrogen Autotransfer
Authors: Labed Amira , Jiang Fan , Labed Ilhem , Lator Alexis , Peters Marius , Achard Mathieu , Kabouche Ahmed , Kabouche Zahia , Sharma Gangavaram V. M. , Bruneau Christian
Published: March 2015

The straightforward and ecofriendly preparation of functionalized julolidines starting from tetrahydroquinoline, diols, and aldehydes, for which water is produced as the only side product was investigated. To achieve this task, several well‐defined ruthenium and iridium complexes including three new complexes were prepared from the corresponding phosphine–sulfonates, phosphine–carboxylates, and phosphine–phosphonates. The first transformation involved in situ generation of enaminoiminium intermediates, which allowed the formation of the julolidines through formal N,C(sp2)‐cyclization of tetrahydroquinoline and the propane‐1,3‐diols. The influence of the chelate acidity points out that [Cp*IrIII]‐based catalysts (Cp*=C5Me5) featuring phosphine–carboxylate and phosphine–sulfonate ligands were suitable for the cyclization, whereas the acidic phosphinophosphonate‐containing complex favored the formation of reduced N‐alkylated tetrahydroquinoline. We found that substitution of the propane‐1,3‐diols was crucial for the generation of enaminoiminium ions, which accounts for the efficiency and selectivity of the reaction. Applying another hydrogen autotransfer process, the prepared julolidines were easily functionalized at the C2 position.
Feasibility of the Constrained Free Energy Method for Modeling NO Formation in Combustion
Authors: Kangas Petteri , Koukkari Pertti , Brink Anders , Hupa Mikko
Published: March 2015

Emissions of nitrogen oxide (NO) from combustion are modeled based on the constrained free energy method (CFE). The CFE method is an extension of the Gibbs' free energy minimization technique, using additional immaterial constraints which allow for the calculation of local thermodynamic equilibria. Chemical reactions, enthalpic effect, and thermochemical state variables are calculated concurrently. Various kinetic constraints were applied in this study for modeling thermal and fuel‐based NO emissions for a number of combustion problems. The results were validated against data obtained from detailed kinetic models. The results indicate that the CFE method can be used for modeling post‐flame thermal and fuel‐based NO emissions. Where more specific estimation of radical buildup, radical overshoot, and ignition delay is needed, however, the accuracy of the applied CFE method was deemed insufficient.
Unique Hydrogen‐Bonded Complex of Hydronium and Hydroxide Ions
Authors: Stapf Manuel , Seichter Wilhelm , Mazik Monika
Published: March 2015

H3O+ and OH−, formed by the self‐ionization of two coordinating water molecules during the crystal growing of a host molecule [1,3,5‐tris(hydroxymethyl)2,4,6‐triethylbenzene (1)], could be effectively stabilized by hydrogen‐bonding interactions with the preorganized hydroxy groups of three molecules of 1. The binding motifs observed in the complex (1)3⋅H3O+⋅HO− show remarkable similarity to those postulated for the hydrated hydronium and hydroxide ion complexes, which play important roles in various chemical, biological, and atmospheric processes, but their molecular structures are still not fully understood and remain a subject of intensive research.
The Metal–Organic Framework MIL‐53(Al) Constructed from Multiple Metal Sources: Alumina, Aluminum Hydroxide, and Boehmite
Authors: Li Zehua , Wu Yi‐nan , Li Jie , Zhang Yiming , Zou Xin , Li Fengting
Published: March 2015

Three aluminum compounds, namely alumina, aluminum hydroxide, and boehmite, are probed as the metal sources for the hydrothermal synthesis of a typical metal–organic framework MIL‐53(Al). The process exhibits enhanced synthetic efficiency without the generation of strongly acidic byproducts. The time‐course monitoring of conversion from different aluminum sources into MIL‐53(Al) is achieved by multiple characterization that reveals a similar but differentiated crystallinity, porosity, and morphology relative to typical MIL‐53(Al) prepared from water‐soluble aluminum salts. Moreover, the prepared MIL‐53(Al) constructed with the three insoluble aluminum sources exhibit an improved thermal stability of up to nearly 600 °C and enhanced yields. Alumina and boehmite are more preferable than aluminum hydroxide in terms of product porosity, yield, and reaction time. The adsorption performances of a typical environmental endocrine disruptor, dimethyl phthalate, on the prepared MIL‐53(Al) samples are also investigated. The improved structural stability of MIL‐53(Al) prepared from these alternative aluminum sources enables double‐enhanced adsorption performance (up to 206 mg g−1) relative to the conventionally obtained MIL‐53(Al).
The N Terminus of α‐Synuclein Forms CuII‐Bridged Oligomers
Authors: Drew Simon C.
Published: March 2015

The 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

Die 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

BACKGROUND

Single‐nucleotide polymorphisms (SNPs) in inflammation, one‐carbon metabolism, and skin cancer genes might influence susceptibility to arsenic‐induced skin lesions.

METHODS

A 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.

RESULTS

In 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).

CONCLUSIONS

Minor 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

A 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.
Quantitative determination of fentanyl in newborn pig plasma and cerebrospinal fluid samples by HPLC‐MS/MS
Authors: Blanco M.E. , Encinas E. , González O. , Rico E. , Vozmediano V. , Suárez E. , Alonso R.M.
Published: March 2015

In this study, a selective and sensitive high performance liquid chromatography‐tandem mass spectrometry (HPLC‐MS/MS) method requiring low sample volume (≤100 μL) was developed and validated for the quantitative determination of the opioid drug fentanyl in plasma and cerebrospinal fluid (CSF). A protein precipitation extraction with acetonitrile was used for plasma samples whereas CSF samples were injected directly on the HPLC column. Fentanyl and 13C6‐fentanyl (Internal Standard) were analyzed in an electrospray ionization source in positive mode, with multiple reaction monitoring (MRM) of the transitions m/z 337.0/188.0 and m/z 337.0/105.0 for quantification and confirmation of fentanyl, and m/z 343.0/188.0 for 13C6‐fentanyl. The respective lowest limits of quantification for plasma and CSF were 0.2 and 0.25 ng/mL. Intra‐ and inter‐assay precision and accuracy did not exceed 15%, in accordance with bioanalytical validation guidelines. The described analytical method was proven to be robust and was successfully applied to the determination of fentanyl in plasma and CSF samples from a pharmacokinetic and pharmacodynamic study in newborn piglets receiving intravenous fentanyl (5 µg/kg bolus immediately followed by a 90‐min infusion of 3 µg/kg/h). Copyright © 2015 John Wiley & Sons, Ltd.
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

Reservoirs 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.
GM‐CSF promotes migration of human monocytes across the blood brain barrier
Authors: Vogel Daphne Y. S. , Kooij Gijs , Heijnen Priscilla D. A. M. , Breur Marjolein , Peferoen Laura A. N. , van der Valk Paul , de Vries Helga E. , Amor Sandra , Dijkstra Christine D.
Published: March 2015

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Infiltration of monocytes into the CNS is crucial for disease onset and progression. Animal studies indicate that granulocyte‐macrophages colony‐stimulating factor (GM‐CSF) may play an essential role in this process, possibly by acting on the migratory capacities of myeloid cells across the blood–brain barrier. This study describes the effect of GM‐CSF on human monocytes, macrophages, and microglia. Furthermore, the expression of GM‐CSF and its receptor was investigated in the CNS under healthy and pathological conditions. We show that GM‐CSF enhances monocyte migration across human blood–brain barrier endothelial cells in vitro. Next, immunohistochemical analysis on human brain tissues revealed that GM‐CSF is highly expressed by microglia and macrophages in MS lesions. The GM‐CSF receptor is expressed by neurons in the rim of combined gray/white matter lesions and astrocytes. Finally, the effect of GM‐CSF on human macrophages was determined, revealing an intermediate activation status, with a phenotype similar to that observed in active MS lesions. Together our data indicate that GM‐CSF is a powerful stimulator of monocyte migration, and is abundantly present in the inflamed CNS where it may act as an activator of macrophages and microglia.
Permutation Testing in the Presence of Polygenic Variation
Authors: Abney Mark
Published: March 2015

This 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.
Regulation of functional expression of the electrogenic sodium bicarbonate cotransporter 1, NBCe1 (SLC4A4), in mouse astrocytes
Authors: Schrödl‐Häußel Magdalena , Theparambil Shefeeq M. , Deitmer Joachim W. , Roussa Eleni
Published: March 2015

The electrogenic sodium bicarbonate cotransporter NBCe1 (SLC4A4) is expressed in many cell types and is a major regulator of intracellular, and extracellular pH. In astrocytes, membrane depolarization leads to intracellular alkalinization through the activation of NBCe1. However, the molecular mechanisms regulating functional expression of NBCe1 in astrocytes are largely unknown. Astrocytes also express voltage‐dependent K+ channels that are activated after depolarization and are sensitive to the K+ blocker 4‐aminopyridine (4AP). Using acute hippocampal slices and primary hippocampal and cortical astrocyte cultures, we have investigated the role of 4AP for the regulation of NBCe1 and elucidated the underlying signaling pathways by quantitative RT‐PCR, immunoblotting, biotinylation of surface proteins, immunofluorescence, and intracellular H+ recording using the H+‐sensitive dye 2′,7′‐bis‐(carboxyethyl)‐5‐(and‐6)‐carboxyfluorescein. The results show significant upregulation of NBCe1 transcript, protein, and surface expression after the application of 4AP in both hippocampal slices and astrocyte cultures, effects that were suppressed after the inhibition of c‐jun N‐terminal kinase (JNK), proto‐oncogene tyrosine‐protein kinase Src, and Src/extracellular‐signal‐regulated kinases signaling. In the presence of 4AP, the rate and amplitude of intracellular H+ changes upon challenging NBCe1 increased in wild‐type astrocytes but not in cortical astrocytes from NBCe1‐deficient mice. 4AP‐dependent effects were suppressed after the inhibition of JNK and Src signaling. Our results demonstrate that transcriptional regulation and targeting of NBCe1, as well as functional operation of NBCe1, may occur through multiple signaling pathways. GLIA 2015;63:1226–1239.
Polysialic acid on SynCAM 1 in NG2 cells and on neuropilin‐2 in microglia is confined to intracellular pools that are rapidly depleted upon stimulation
Authors: Werneburg Sebastian , Mühlenhoff Martina , Stangel Martin , Hildebrandt Herbert
Published: March 2015

NG2 cells comprise a heterogeneous precursor population but molecular markers distinguishing between the assumed NG2 cell subpopulations are lacking. Previously, we described that a subfraction of the synaptic cell adhesion molecule SynCAM 1 is modified with the glycan polysialic acid (polySia) in NG2 cells. As for its major carrier, the neural cell adhesion molecule NCAM, polySia attenuates SynCAM 1 adhesion. Functions, as well as cellular and subcellular distribution of polySia‐SynCAM 1 are elusive. Using murine glial cultures we now demonstrate that polySia‐SynCAM 1 is confined to the Golgi compartment of a subset of NG2 cells and transiently recruited to the cell surface in response to depolarization. NG2 cells with Golgi‐confined polySia were NCAM‐negative, but positive for markers of oligodendrocyte precursor cells (OPCs). Consistent with previous data on polySia‐SynCAM 1, polySia in Ncam−/− NG2 cells was exclusively attached to N‐glycans and synthesized by ST8SIA2, one out of two mammalian polysialyltransferases. Unexpectedly, Golgi‐confined polySia was also detected in Ncam−/− microglia, but this fraction resided on O‐glycans and was produced by the second polysialyltransferase, ST8SIA4, indicating the presence of yet another polySia carrier in microglia. Searching for this carrier, we identified polysialylated neuropilin‐2, so far only known from dendritic cells and exudate macrophages. Microglia activation by LPS, but not interleukin‐4, caused a transient translocation of Golgi‐localized polySia to the cell surface, resulting in complete depletion. Finally, NO‐production of LPS‐stimulated microglia was attenuated by addition of polySia suggesting that the observed loss of polySia‐neuropilin‐2 is involved in negative feedback regulation of pro‐inflammatory microglia polarization. GLIA 2015;63:1240–1255
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

Traditionally, 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

Integrated 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.
Imagining a Future for the Planet Through Literature, Writing, Images, and Drama
Authors: Beach Richard
Published: March 2015

This Commentary posits the need to analyze how the energy/transportation, agricultural/food, and economic/political systems influence climate change through responding to literary “cli‐fi” texts, place‐based writing, visual representation of the effects of climate change, and drama activities.
Going Public
Authors: Lammers Jayne C. , Marsh Valerie L.
Published: March 2015

Building 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.
The topology of the Ehrenfest force density revisited. A different perspective based on Slater‐type orbitals
Authors: Dillen Jan
Published: March 2015

The topology of the Ehrenfest force density was studied with Slater‐type orbitals (STO). At larger distances from the nuclei, STOs generate similar artefacts as noticed before with Gaussian‐type orbitals. The topology of the Ehrenfest force density was found to be mainly homeomorphic with the topology of the electron density. For the first time, reliable integrations of several properties over force density atomic basins were performed successfully. Integration of the electron density of a number of hydrides, fluorides, and chlorides of first row elements over force density basins indicate substantial differences between the partial charges of the atoms as compared with those obtained from electron density basins. Calculations on saturated hydrocarbons confirm that the electronegativity of carbon atoms increases with increasing geometrical strain. Atomic interaction lines are observed to exist in the Ehrenfest force density between the hydrogen atoms of several so‐called “congested” molecules, and also in some inclusion complexes of alkanes with helium. However, interaction lines are lacking in several other controversial cases. © 2015 Wiley Periodicals, Inc.
Extreme daily precipitation events at Spitsbergen, an Arctic Island
Authors: Serreze Mark C. , Crawford Alex D. , Barrett Andrew P.
Published: March 2015

Daily 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

Background

Tranexamic 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.

Aim

To increase awareness of the association between tranexamic acid and acute myocardial infarction.

Clinical details

A 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.

Outcome

The 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.

Conclusion

This 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

Aim

To identify the types and severity of drug‐related problems (DRPs) identified by a pharmacist in a thoracic outpatient clinic.

Methods

A 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.

Results

A 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.

Conclusion

There 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

Background

People 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.

Aim

To 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.

Method

Consumers were recruited from five community pharmacies in Brisbane, Australia and invited to participate in a structured interview.

Results

A 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.

Conclusion

Some 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

Background

Although 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.

Aim

This 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.

Discussion

Available 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.

Conclusion

To 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.
Role of pharmacists in optimising medication management during pregnancy and lactation
Authors: Grzeskowiak Luke E.
Published: March 2015

Pregnancy and lactation has a unique effect on decisions relating to medication use. Medication safety can often be a great source of concern for women and healthcare professionals alike, leading to decisions that can negatively impact on outcomes. Compounding this is that evidence regarding the benefits and risks of medication use in pregnancy and lactation can often be lacking, contradictory or difficult to interpret and apply to clinical practice. Pharmacists represent a key source of information on medication use in pregnancy and lactation and as such play an essential role in optimising medication use. Notably, the role of pharmacists extends well beyond that of addressing concerns relating to medication safety, and includes contributing towards therapeutic decision making, providing ongoing medication management, and influencing patterns of medication use. Opportunities for improving health outcomes for mothers and their babies are aplenty and the time has come for pharmacists to stand up to the challenge and play their role.
Comb‐Like Graft Copolymers of Poly(oxa)norbornene: Efficient Synthesis Using a Combination of ROMP and Click Chemistry
Authors: Eissa Ahmed M. , Khosravi Ezat
Published: March 2015

The combination of ring‐opening metathesis polymerization (ROMP) and copper‐catalyzed azide–alkyne cycloaddition (CuAAC) is described as an efficient click reaction to synthesize a new range of well‐defined comb‐like polynorbornene/polyoxanorbornene graft copolymers containing poly(ethylene glycol) (PEG) and/or poly(ε‐caprolactone) (PCL) as side chains. The “grafting through” method is applied for the synthesis of polyoxanorbornene‐g‐PEG via ROMP of oxanorbornenyl di‐PEG macromonomer prepared by click coupling of azide‐terminated PEG with di‐alkyne‐functionalized oxanorbornene. The well‐characterized macromonomer is then subjected to ROMP. Polynorbornene‐g‐PCL and polynorbornene‐g‐PEG are prepared by the “grafting onto” route. This is achieved by ROMP of 5‐bromohexyloxymethyl norbornene followed by reaction with NaN3 and then click reaction with alkyne‐terminated PEG and PCL. (Polyoxanorbornene‐g‐PEG)‐ran‐(polynorbornene‐g‐PCL) is prepared by ROMP of a mixture of oxanorbornenyl di‐PEG and 5‐bromohexyloxymethyl norbornene followed by reaction with NaN3 and subsequently click reaction with alkyne‐end‐capped PCL. All intermediates and final products are characterized by IR, NMR, MS, and size exclusion chromatography (SEC). Self‐assembly of these comb‐like polymers in solution into micro/nanostructures is foreseen, leading to a wide range of potential applications.

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A Timoshenko finite element straight beam with internal degrees of freedom
Authors: Caillerie Denis , Kotronis Panagiotis , Cybulski Robert
Published: March 2015

We present hereafter the formulation of a Timoshenko finite element straight beam with internal degrees of freedom, suitable for nonlinear material problems in geomechanics (e.g., beam type structures and deep pile foundations). Cubic shape functions are used for the transverse displacements and quadratic for the rotations. The element is free of shear locking, and we prove that one element is able to predict the exact tip displacements for any complex distributed loadings and any suitable boundary conditions. After the presentation of the virtual power and the weak form formulations, the construction of the elementary stiffness matrix is detailed. The analytical results of the static condensation method are provided. It is also proven that the element introduced by Friedman and Kosmatka in , with shape functions depending on material properties, is derived from the new beam element. Validation is provided using linear and material nonlinear applications (reinforced concrete column under cyclic loading) in the context of a multifiber beam formulation. Copyright © 2015 John Wiley & Sons, Ltd.
Excess body mass index‐ and waist circumference‐years and incident cardiovascular disease: The CARDIA study
Authors: Reis Jared P. , Allen Norrina , Gunderson Erica P. , Lee Joyce M. , Lewis Cora E. , Loria Catherine M. , Powell‐Wiley Tiffany M. , Rana Jamal S. , Sidney Stephen , Wei Gina , Yano Yuichiro , Liu Kiang
Published: March 2015

Objective

To determine the influence of the total cumulative exposure to excess overall and abdominal adiposity on the incidence of cardiovascular disease (CVD).

Methods

Prospective study of 4,061 white and black adults without CVD at baseline in 1985‐1986 (age 18‐30 years) from the multicenter, community‐based CARDIA study. Time‐varying excess body mass index (BMI)‐ and waist circumference (WC)‐years were calculated as products of the degree and duration of excess overall (BMI ≥ 25 kg/m2) and abdominal adiposity [WC >94 cm (men) and >80 cm (women)], respectively, collected at up to eight examinations.

Results

During a median of 24.8 years, there were 125 incident CVD, 62 coronary heart disease (CHD), and 33 heart failure (HF) events. Adjusted hazard ratios for CVD, CHD, and HF for each additional 50 excess BMI‐years were 1.20 (1.08, 1.34), 1.25 (1.07, 1.46), and 1.45 (1.23, 1.72), respectively. For each 50 excess WC‐years, these hazard ratios were 1.10 (1.04, 1.18), 1.13 (1.03, 1.24), and 1.22 (1.11, 1.34), respectively. Akaike information criterion values were lowest in models containing time‐varying excess BMI‐ or WC‐years compared to those including time‐varying BMI or WC only.

Conclusions

Excess BMI‐ and WC‐years are predictors of the risk of CVD and may provide a better indicator of the cumulative exposure to excess adiposity than BMI or WC only.
Fat distribution and mortality: The AGES‐Reykjavik study
Authors: Koster Annemarie , Murphy Rachel A. , Eiriksdottir Gudny , Aspelund Thor , Sigurdsson Sigurdur , Lang Thomas F. , Gudnason Vilmundur , Launer Lenore J. , Harris Tamara B.
Published: March 2015

Objective

This study examined associations of regional fat depots with all‐cause mortality over 11 years of follow‐up.

Methods

Data were from 2,187 men and 2,900 women, aged 66‐96 years in the AGES‐Reykjavik Study. Abdominal visceral fat and subcutaneous fat and thigh intermuscular fat and subcutaneous fat were measured by CT.

Results

In men, every standard deviation (SD) increment in thigh intermuscular fat was related to a significantly greater mortality risk (HR: 1.17, 95% CI: 1.08‐1.26) after adjustment for age, education, smoking, physical activity, alcohol, BMI, type 2 diabetes, and coronary heart disease. In women, visceral fat (per SD increment) significantly increased mortality risk (HR: 1.13, 95% CI: 1.03‐1.25) while abdominal subcutaneous fat (per SD increment) was associated with a lower mortality risk (HR: 0.70, 95% CI: 0.61‐0.80). Significant interactions with BMI were found in women, indicating that visceral fat was a strong predictor of mortality in obese women while abdominal and thigh subcutaneous fat were associated with a lower mortality risk in normal‐weight and overweight women.

Conclusions

Fat distribution is associated with mortality over 11 years of follow‐up independent of overall fatness. The divergent mortality risks for visceral fat and subcutaneous fat in women suggest complex relationships between overall fatness and mortality.