bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Clinical Legal Education’— Observing, Comparing and Analyzing the Differences in Germany and China for each other’s Respective Advantages
Authors: Hannemann Jan-Gero Alexander , Lampe Jan Hendrik
Published: June 2015

‘Clinical Legal Education’ in Germany and China is a new approach towards changing (one might even say completing) law studies and the curriculum at universities. It provides a lot of opportunities and benefits for the participating students and thereby for the broader community. Adapted from US legal clinics, clinical legal education has changed within the last few years both legal systems and legal education. The surprisingly strong development in Germany and China which could not be more different shows many interesting aspects on how to build up legal clinics and how to influence the society within. In both countries education used to be dominated by theory. Practical matters were not, or at least not for students taken into consideration for a sufficient amount of time.

The authors attempt to compare and analyze the development of clinical legal education and student legal services in China and Germany.

This analysis provides a broad approach from the historical roots to the development and thereby influence of the national umbrella organizations and cross-border influences.

One does not only find many similarities, but also discovers a common understanding of legal clinical education as well as differences that can be used to understand one’s own legal clinic system and develop it further. This analysis provides the possibility to strengthen the global development of ‘clinical legal education’.
Marrying microfluidics and microwells for parallel, high-throughput single-cell genomics
Authors: Wadsworth Marc H. , Hughes Travis K. , Shalek Alex K.
Published: June 2015

An innovative, microwell-based platform for single-cell RNA sequencing (RNA-seq) combines cost efficiency, scalability and parallelizability, and will enable many new avenues of biological inquiry.

See related Research article: http://dx.doi.org/10.1186/s13059-015-0684-3
Restoration of mesenchymal retinal pigmented epithelial cells by TGFβ pathway inhibitors: implications for age-related macular degeneration
Authors: Radeke Monte J. , Radeke Carolyn M. , Shih Ying-Hsuan , Hu Jane , Bok Dean , Johnson Lincoln V. , Coffey Pete J.
Published: June 2015

Background

Age-related macular degeneration (AMD) is a leading cause of blindness. Most vision loss occurs following the transition from a disease of deposit formation and inflammation to a disease of neovascular fibrosis and/or cell death. Here, we investigate how repeated wound stimulus leads to seminal changes in gene expression and the onset of a perpetual state of stimulus-independent wound response in retinal pigmented epithelial (RPE) cells, a cell-type central to the etiology of AMD.

Methods

Transcriptome wide expression profiles of human fetal RPE cell cultures as a function of passage and time post-plating were determined using Agilent 44 K whole genome microarrays and RNA-Seq. Using a systems level analysis, differentially expressed genes and pathways of interest were identified and their role in the establishment of a persistent mesenchymal state was assessed using pharmacological-based experiments.

Results

Using a human fetal RPE cell culture model that considers monolayer disruption and subconfluent culture as a proxy for wound stimulus, we show that prolonged wound stimulus leads to terminal acquisition of a mesenchymal phenotype post-confluence and altered expression of more than 40 % of the transcriptome. In contrast, at subconfluence fewer than 5 % of expressed transcripts have two-fold or greater expression differences after repeated passage. Protein-protein and pathway interaction analysis of the genes with passage-dependent expression levels in subconfluent cultures reveals a 158-node interactome comprised of two interconnected modules with functions pertaining to wound response and cell division. Among the wound response genes are the TGFβ pathway activators: TGFB1, TGFB2, INHBA, INHBB, GDF6, CTGF, and THBS1. Significantly, inhibition of TGFBR1/ACVR1B mediated signaling using receptor kinase inhibitors both forestalls and largely reverses the passage-dependent loss of epithelial potential; thus extending the effective lifespan by at least four passages. Moreover, a disproportionate number of RPE wound response genes have altered expression in neovascular and geographic AMD, including key members of the TGFβ pathway.

Conclusions

In RPE cells the switch to a persistent mesenchymal state following prolonged wound stimulus is driven by lasting activation of the TGFβ pathway. Targeted inhibition of TGFβ signaling may be an effective approach towards retarding AMD progression and producing RPE cells in quantity for research and cell-based therapies.
Timing and causes of death in septic shock
Authors: Daviaud Fabrice , Grimaldi David , Dechartres Agnès , Charpentier Julien , Geri Guillaume , Marin Nathalie , Chiche Jean-Daniel , Cariou Alain , Mira Jean-Paul , Pène Frédéric
Published: June 2015

Background

Most studies about septic shock report a crude mortality rate that neither distinguishes between early and late deaths nor addresses the direct causes of death. We herein aimed to determine the modalities of death in septic shock.

Methods

This was a 6-year (2008–2013) monocenter retrospective study. All consecutive patients diagnosed for septic shock within the first 48 h of intensive care unit (ICU) admission were included. Early and late deaths were defined as occurring within or after 3 days following ICU admission, respectively. The main cause of death in the ICU was determined from medical files. A multinomial logistic regression analysis using the status alive as the reference category was performed to identify the prognostic factors associated with early and late deaths.

Results

Five hundred forty-three patients were included, with a mean age of 66 ± 15 years and a high proportion (67 %) of comorbidities. The in-ICU and in-hospital mortality rates were 37.2 and 45 %, respectively. Deaths occurred early for 78 (32 %) and later on for 166 (68 %) patients in the ICU (n = 124) or in the hospital (n = 42). Early deaths were mainly attributable to intractable multiple organ failure related to the primary infection (82 %) and to mesenteric ischemia (6.4 %). In-ICU late deaths were directly related to end-of-life decisions in 29 % of patients and otherwise mostly related to ICU-acquired complications, including nosocomial infections (20.4 %) and mesenteric ischemia (16.6 %). Independent determinants of early death were age, malignancy, diabetes mellitus, no pathogen identification, and initial severity. Among 3-day survivors, independent risk factors for late death were age, cirrhosis, no pathogen identification, and previous corticosteroid treatment.

Conclusions

Our study provides a comprehensive assessment of septic shock-related deaths. Identification of risk factors of early and late deaths may determine differential prognostic patterns.
A 2015 International Geomagnetic Reference Field (IGRF) candidate model based on Swarm’s experimental absolute magnetometer vector mode data
Authors: Vigneron Pierre , Hulot Gauthier , Olsen Nils , Léger Jean-Michel , Jager Thomas , Brocco Laura , Sirol Olivier , Coïsson Pierdavide , Lalanne Xavier , Chulliat Arnaud , Bertrand François , Boness Axel , Fratter Isabelle
Published: June 2015

Each of the three satellites of the European Space Agency Swarm mission carries an absolute scalar magnetometer (ASM) that provides the nominal 1-Hz scalar data of the mission for both science and calibration purposes. These ASM instruments, however, also deliver autonomous 1-Hz experimental vector data. Here, we report on how ASM-only scalar and vector data from the Alpha and Bravo satellites between November 29, 2013 (a week after launch) and September 25, 2014 (for on-time delivery of the model on October 1, 2014) could be used to build a very valuable candidate model for the 2015.0 International Geomagnetic Reference Field (IGRF). A parent model was first computed, describing the geomagnetic field of internal origin up to degree and order 40 in a spherical harmonic representation and including a constant secular variation up to degree and order 8. This model was next simply forwarded to epoch 2015.0 and truncated at degree and order 13. The resulting ASM-only 2015.0 IGRF candidate model is compared to analogous models derived from the mission’s nominal data and to the now-published final 2015.0 IGRF model. Differences among models mainly highlight uncertainties enhanced by the limited geographical distribution of the selected data set (essentially due to a lack of availability of data at high northern latitude satisfying nighttime conditions at the end of the time period considered). These appear to be comparable to differences classically observed among IGRF candidate models. These positive results led the ASM-only 2015.0 IGRF candidate model to contribute to the construction of the final 2015.0 IGRF model.
Combining spatial components and Hilbert transforms to interpret ground-time-domain electromagnetic data
Authors: Desmarais Jacques K. , Smith Richard S.
Published: June 2015

We have developed a method for displaying or imaging data from a ground-time-domain electromagnetic system and for extracting the geometric parameters of a small conductor. The parameters are determined directly from the data using combinations of the spatial components of the secondary fields and their Hilbert transforms. The position of the target coincides with the peaks of the energy envelope (EE) or the [Formula: see text]-component of the response. Here, the EE is the square root of the sum of the squares of the three spatial components and their Hilbert transforms, whereas the [Formula: see text]-component response is an analogous quantity that excludes the Hilbert transform terms. Studies on synthetic models indicate that the [Formula: see text]-component response is sharper than the EE in most possible target orientations. Once the position of a body has been determined using the peak of the [Formula: see text]-component response, the dip of the target can be quantified using the ratio of the full-width at half-magnitude (FWHM) of the [Formula: see text]-component response and the [Formula: see text]-component Hilbert transform response, which is analogous to the EE but excludes the untransformed quantities. Finally, once all other geometric parameters have been determined, the depth of the target can be evaluated using the FWHM of the [Formula: see text]-component response. The proposed modeling method was tested over an anomaly acquired at the Coulon field site during an InfiniTEM survey in the Abitibi greenstone belt of Quebec. The extracted geometric parameters were consistent with the available geologic information.
Physical exercise and internet-based cognitive–behavioural therapy in the treatment of depression: Randomised controlled trial
Authors: Hallgren Mats , Kraepelien Martin , öjehagen Agneta , Lindefors Nils , Zeebari Zangin , Kaldo Viktor , Forsell Yvonne
Published: June 2015

Background

Depression is common and tends to be recurrent. Alternative treatments are needed that are non-stigmatising, accessible and can be prescribed by general medical practitioners.

Aims

To compare the effectiveness of three interventions for depression: physical exercise, internet-based cognitive–behavioural therapy (ICBT) and treatment as usual (TAU). A secondary aim was to assess changes in self-rated work capacity.

Method

A total of 946 patients diagnosed with mild to moderate depression were recruited through primary healthcare centres across Sweden and randomly assigned to one of three 12-week interventions (trail registry: KCTR study ID: KT20110063). Patients were reassessed at 3 months (response rate 78%).

Results

Patients in the exercise and ICBT groups reported larger improvements in depressive symptoms compared with TAU. Work capacity improved over time in all three groups (no significant differences).

Conclusions

Exercise and ICBT were more effective than TAU by a general medical practitioner, and both represent promising non-stigmatising treatment alternatives for patients with mild to moderate depression.
Auditory hair cell defects as potential cause for sensorineural deafness in Wolf-Hirschhorn syndrome
Authors: Ahmed Mohi , Ura Kiyoe , Streit Andrea
Published: June 2015

WHSC1 is a histone methyltransferase (HMT) that catalyses the addition of methyl groups to lysine 36 on histone 3. In humans, WHSC1 haploinsufficiency is associated with all known cases of Wolf-Hirschhorn syndrome (WHS). The cardinal feature of WHS is a craniofacial dysmorphism, which is accompanied by sensorineural hearing loss in 15% of patients. Here, we show that WHSC1-deficient mice display craniofacial defects that overlap with WHS including cochlea anomalies. While auditory hair cells are specified normally, their stereocilia hair bundles required for sound perception, fail to develop the appropriate morphology. Furthermore, the orientation and cellular organisation of cochlear hair cells and their innervation are defective. These findings identify, for the first time, the likely cause of sensorineural hearing loss in WHS patients.
Effects of FSGS-associated mutations on the stability and function of myosin-1 in fission yeast
Authors: Bi Jing , Carroll Robert T. , James Michael L. , Ouderkirk Jessica L. , Krendel Mira , Sirotkin Vladimir
Published: June 2015

Point mutations in the human MYO1E gene, encoding class I myosin Myo1e, are associated with focal segmental glomerulosclerosis (FSGS), a primary kidney disorder that leads to end stage kidney disease. In this study, we used a simple model organism, fission yeast Schizosaccharomyces pombe, to test the effects of FSGS-associated mutations on myosin activity. Fission yeast has only one class I myosin, Myo1, which is involved in actin patch assembly at the sites of endocytosis. The amino acid residues mutated in the FSGS patients are conserved between human Myo1e and yeast Myo1, which allowed us to introduce equivalent mutations into yeast myosin and use the resulting mutant strains for functional analysis. Yeast strains expressing mutant Myo1 exhibited defects in growth and endocytosis similar to those observed in the myo1 deletion strain. These mutations also disrupted Myo1 localization to endocytic actin patches and resulted in mis-localization of Myo1 to eisosomes, linear membrane microdomains found in yeast cells. While both mutants examined in this study exhibited loss of function, one of these mutants was also characterized by the decreased protein stability. Thus, using the yeast model system we were able to determine that the kidney disease-associated mutations impair myosin functional activity and have differential effects on protein stability.
Glycogen synthase kinase-3 inhibition attenuates fibroblast activation and development of fibrosis following renal ischemia/reperfusion in mice
Authors: Singh Shailendra P. , Tao Shixin , Fields Timothy A. , Webb Sydney , Harris Raymond C. , Rao Reena
Published: June 2015

Glycogen synthase kinase-3β (GSK3β) is a serine/threonine protein kinase that plays an important role in renal tubular injury and regeneration in acute kidney injury. However its role in the development of renal fibrosis, often a long-term consequence of acute kidney injury is unknown. Using a mouse model of renal fibrosis induced by ischemia/reperfusion injury, we demonstrate increased GSK3β expression and activity in fibrotic kidneys and its presence in myofibroblasts in addition to tubular epithelial cells. Pharmacological inhibition of GSK3 using TDZD-8 starting before or after ischemia/reperfusion significantly suppressed renal fibrosis by reducing myofibroblast population, collagen-1 and fibronectin deposition, inflammatory cytokines and macrophage infiltration. GSK3 inhibition in vivo reduced TGF-β1, SMAD3 activation and plasminogen activator inhibitor-1 levels. Consistently in vitro, TGF-β1 treatment increased GSK3β expression and GSK3 inhibition abolished TGF-β1 induced SMAD3 activation and α-smooth muscle actin expression in cultured renal fibroblasts. Importantly, overexpression of constitutively active GSK3β stimulated α-smooth muscle actin expression even in the absence of TGF-β1 treatment. These results suggest that TGF-β regulates GSK3β, which in turn is important for TGF-β/SMAD3 signaling and fibroblast-to-myofibroblast differentiation. Overall these studies demonstrate that GSK3 could promote renal fibrosis by activation of TGF-β signaling and the use of GSK3 inhibitors might represent a novel therapeutic approach for progressive renal fibrosis that develops as a consequence of acute kidney injury.
XROMM analysis of tooth occlusion and temporomandibular joint kinematics during feeding in juvenile miniature pigs
Authors: Menegaz Rachel A. , Baier David B. , Metzger Keith A. , Herring Susan W. , Brainerd Elizabeth L.
Published: June 2015

Like humans, domestic pigs are omnivorous and thus are a common model for human masticatory function. Prior attempts to characterize food-tooth interactions and jaw movements associated with mastication have been limited to aspects of the oral apparatus that are visible externally (with videography) and/or to 2D movements of oral structures (with monoplanar videofluoroscopy). We used XROMM, a 3D technique that combines CT-based morphology with biplanar videofluoroscopy, to quantify mandibular kinematics, tooth occlusion, and mandibular condylar displacements within the temporomandibular joint during feeding. We observed that the pig TMJ moved detectably in only 3 of 6 possible degrees of freedom during mastication: 2 rotations, pitch and yaw; and 1 translation, protraction-retraction. Asymmetrical yaw around a dorsoventral axis produced the observed alternating left-right chewing cycles responsible for food reduction. Furthermore, the relative motions of the upper and lower premolars contained a substantial mesiodistal component in addition to the buccolingual component, resulting in an oblique (rather than a strictly transverse) power stroke. This research demonstrates the capacity of XROMM to explore the kinematic underpinnings of key masticatory movements, such as the occlusal power stroke, by integrating tooth, joint, and rigid body jaw movements. XROMM also allowed us to test kinematic hypotheses based on skeletal anatomy with actual kinematics observed during naturalistic feeding behaviors. We observed that the soft tissue structures of the TMJ appear to play a significant role in limiting the range of motion of a joint, and thus analyses based solely on osseous morphology may over-estimate joint mobility.
Aluminum Monocation Basicity and Affinity Scales
Authors: Gal Jean-François , Yáñez Manuel , Mó Otilia
Published: June 2015

The experimental aspects of the determination of thermochemical data for the attachment of the aluminum monocation Al+ to neutral atoms and molecules are reviewed. Literature aluminum cation affinities (enthalpy scale) and basicities (Gibbs energy scale) are tabulated and discussed. Ab initio quantum chemical calculations at the G4 level on 43 adducts provide a consistent picture of the energetics of the adducts and their structures. The Al+-ligand bonding is analyzed in terms of natural bond orbital and atom-in molecule analyses. A brief comparison of the Al+ basicity scales and other gas-phase cation basicities is presented.
Reactions of Stabilized Aliphatic Carbanions with Esters of Formic Acid in the Gas Phase
Authors: Wileńska Beata , Świder Paweł , Danikiewicz Witold
Published: June 2015

The reactions of nitromethane, acetonitrile, and ethyl acetate carbanions with formic acid esters were investigated in the gas phase by mass spectrometry and quantum chemical calculations. It was found that the carbanion of nitromethane practically does not react with formic acid esters and only traces of the Claisen-type addition–elimination reaction product were observed. In the case of the deprotonated acetonitrile, the Claisen-type condensation that yielded the carbanion of cyanoacetaldehyde proceeded almost quantitatively for all the studied formates. Other products, like the Riveros reaction product, were observed in minor amounts. The ethyl acetate carbanion reacts with formates in a much more complex way because it decomposes in a collision cell, yielding the deprotonated ketene anion, which also can react with formic acid esters. Consequently, the Claisen condensation reaction products of both anions were observed as well as the products of other reactions. All the proposed reaction pathways were confirmed by quantum chemical calculations, including the transition-state energies.
Gas-Phase Reactions of the Rhenium Oxide Anions, [ReOx]− (x = 2–4) with the Neutral Organic Substrates Methane, Ethene, Methanol and Acetic Acid
Authors: Canale Valentino , Zavras Athanasios , Khairallah George N. , d'Alessandro Nicola , O'Hair Richard A.J.
Published: June 2015

The ion–molecule reactions of the rhenium oxide anions, [ReO x]− ( x = 2–4) with the organic substrates methane, ethene, methanol, and acetic acid have been examined in a linear ion trap mass spectrometer. The only reactivity observed was between [ReO2]− and acetic acid. Isotope-labelled experiments and high-resolution mass spectrometry measurements were used to assign the formulas of the ionic products. Collision-induced dissociation and ion–molecule reactions with acetic acid were used to probe the structures of the mass-selected primary product ions. Density functional theory calculations [PBE0/LanL2DZ6-311+G(d)] were used to suggest possible structures. The three primary product channels observed are likely to arise from the formation of the metallalactone [ReO2(CH2CO2)]− ( m/z 277) and H2, [CH3ReO2(OH)]− ( m/z 251) and CO, and [ReO3]− ( m/z 235), H2 and CH2CO.
Composition, Sequencing and Ion Mobility Mass Spectrometry of Heparan Sulfate-like Octasaccharide Isomers Differing in Glucuronic and Iduronic Acid Content
Authors: Miller Rebecca L. , Wei Wei , Schwörer Ralf , Zubkova Olga V. , Tyler Peter C. , Turnbull Jeremy E. , Leary Julie A.
Published: June 2015

Here we report ion mobility mass spectrometry (IMMS) separation and tandem mass spectrometry (MS2) sequencing methods used to analyze and differentiate six synthetically produced heparin/heparan sulfate (HS)-like octasaccharide (dp8) isomeric structures. These structures are isomeric with regard to either glucuronic acid (GlcA) or iduronic acid (IdoA) residues at various positions. IMMS analysis showed that a fully GlcA structure exhibited a more compact conformation, whereas the fully IdoA structure was more extended. Interestingly, the change from IdoA to GlcA in specific locations resulted in strong conformational distortions. MS2 of the six isomers showed very different spectra with unique sets of diagnostic product ions. Analysis of MS2 product ion spectra suggests that the GlcA group correlated with the formation of a glycosidic product ion under lower energy conditions. This resulted in an earlier product ion formation and more intense product ions. Importantly, this knowledge enabled a complete sequencing of the positions of GlcA and IdoA in each of the four positions located in each unique dp8 structure.
Native Top-down Mass Spectrometry for the Structural Characterization of Human Hemoglobin
Authors: Zhang Jiang , Malmirchegini G. Reza , Clubb Robert T. , Loo Joseph A.
Published: June 2015

Native mass spectrometry (MS) has become an invaluable tool for the characterization of proteins and noncovalent protein complexes under near physiological solution conditions. Here we report the structural characterization of human hemoglobin (Hb), a 64 kDa oxygen-transporting protein complex, by high-resolution native top-down MS using electrospray ionization and a 15-Tesla Fourier transform ion cyclotron resonance mass spectrometer. Native MS preserves the noncovalent interactions between the globin subunits, and electron-capture dissociation (ECD) produces fragments directly from the intact Hb complex without dissociating the subunits. Using activated ion ECD, we observe the gradual unfolding process of the Hb complex in the gas phase. Without protein ion activation, the native Hb shows very limited ECD fragmentation from the N-termini, suggesting a tightly packed structure of the native complex and therefore a low fragmentation efficiency. Precursor ion activation allows a steady increase in N-terminal fragment ions, while the C-terminal fragments remain limited (38 c ions and four z ions on the α chain; 36 c ions and two z ions on the β chain). This ECD fragmentation pattern suggests that, upon activation, the Hb complex starts to unfold from the N-termini of both subunits, whereas the C-terminal regions and therefore the potential regions involved in the subunit binding interactions remain intact. ECD-MS of the Hb dimer shows similar fragmentation patterns as the Hb tetramer, providing further evidence for the hypothesized unfolding process of the Hb complex in the gas phase. Native top-down ECD-MS allows efficient probing of the Hb complex structure and subunit binding interactions in the gas phase. It may provide a fast and effective means to probe the structure of novel protein complexes that are intractable to traditional structural characterization tools.
Comparison of the Applicability of Mass Spectrometer Ion Sources Using a Polarity—Molecular Weight Scattergram with a 600-Sample In-House Chemical Library
Authors: Sugimura Natsuhiko , Furuya Asami , Yatsu Takahiro , Shibue Toshimichi
Published: June 2015

To provide a practical guideline for the selection of a mass spectrometer ion source, we compared the applicability of three types of ion source: direct analysis in real time (DART), electrospray ionization (ESI) and fast atom bombardment (FAB), using an in-house high-resolution mass spectrometry sample library consisting of approximately 600 compounds. The great majority of the compounds (92%), whose molecular weights (MWs) were broadly distributed between 150 and 1000, were detected using all the ion sources. Nevertheless, some compounds were not detected using specific ion sources. The use of FAB resulted in the highest sample detection rate (>98%), whereas the detection rates obtained using DART and ESI were slightly lower (>96%). A scattergram constructed using MW and topological polar surface area (tPSA) as a substitute for molecular polarity showed that the performance of ESI was weak in the low-MW (<400), low-polarity (tPSA < 60) area, whereas the performance of DART was weak in the high-MW (>800) area. These results might provide guidelines for the selection of ion sources for inexperienced mass spectrometry users.
Measurement of Soluble Solids Content of Three Fruit Species Using Universal near Infrared Spectroscopy Models
Authors: Liu Ran , Qi Shuye , Lu Jie , Han Donghai
Published: June 2015

Based on the similar physical and chemical properties of Fuji apples, Okubo peaches and Hosui pears, universal near infrared spectroscopy models were developed to measure the fruits' soluble solids content (SSC). The second derivative eliminated the baseline drift caused by different integration times. The effective wavebands of the three species were selected by moving window partial least-squares (MWPLS) regression, and the effective wavebands were combined to develop a universal partial least-squares regression (PLS) model. Then, the effective wavelengths (876 nm, 890 nm and 900 nm) were identified by the successive projections algorithm (SPA) from the combined region (840–920 nm) to develop a multiple linear regression (MLR) model. The coefficient of determination of calibration ( R2) and validation ( r2) were 0.96 and 0.97, and the root mean square error of calibration ( RMSEC) and validation ( RMSEP) were 0.47 °Brix and 0.45 °Brix, respectively, for the PLS model and 0.96 °Brix, 0.96 °Brix and 0.49 °Brix and 0.46 °Brix, respectively, for the MLR model. The universal models were greatly simplified by variable selection and proved to be practical for the prediction of SSC in the three fruit species.
Using Visible and near Infrared Spectroscopy to Estimate Carbonates and Gypsum in Soils in Arid and Subhumid Regions of Isfahan, Iran
Authors: Khayamim Fatemah , Wetterlind Johanna , Khademi Hossein , Robertson A.H. Jean , Cano Angel Faz , Stenberg Bo
Published: June 2015

Soils in arid and semi-arid regions are strongly affected by the accumulation of carbonates, gypsum and other, more soluble, salts. Carbonates and gypsum both have a considerable influence on soil properties, especially the chemical properties of the soil solution. The development of reliable, fast and inexpensive methods to quantify the amounts of carbonates and gypsum in soil is therefore important. Visible and near infrared (vis-NIR) spectroscopy is a non-destructive, rapid and cheap method for measuring several soil properties simultaneously. However, research on vis-NIR spectroscopy in quantifying carbonates and gypsum is limited. Therefore, this study evaluated the efficiency of vis-NIR spectroscopy in quantifying carbonates and gypsum in surface soils using partial least-squares regression (PLSR) compared with standard laboratory methods and compared PLSR with a feature-specific method using continuum removal (CR). Carbonates and gypsum in a total of 251 sieved and air-dried topsoil samples from Isfahan Province in central Iran were measured by standard laboratory methods and vis-NIR spectroscopy (350–2500 nm wavelength range). In parallel, PLSR and the feature- specific method based on CR spectra were used to predict carbonates and gypsum. The PLSR model efficiency ( E) for carbonates and gypsum in the validation set was 0.52 and 0.80, respectively. The PLSR model resulted in better predictions than the feature-specific method for both soil properties. Because of the unique absorption features of gypsum, which did not overlap with other soil properties, predictions of gypsum resulted in higher E values and lower errors than predictions of carbonates.
Managing Human Resources and Technology Innovation: The Impact of Process and Outcome Uncertainties
Authors: Peter Altmann , Robert Engberg
Published: June 2015

High technology innovation performance relies on a skilful utilization of human resources. The main purpose of this paper is to explore the impact of interpreted outcome and process uncertainties on the effective management of human resources for technology innovation. This is achieved through an insider-outsider based case study approach of three medical device innovations with varying degrees of radicalness. Findings suggest that uncertainties in process and outcome strongly influence what constitutes effective management of human resources for technology innovation. Findings also offer insights into when certain innovation theories hold, and suggestions on how to manage human resources and technology innovation under various conditions of uncertainty.
Studies of alternative isoforms provide insight into TDP-43 autoregulation and pathogenesis
Authors: D'Alton Simon , Altshuler Marcelle , Lewis Jada
Published: June 2015

TDP-43 is a soluble, nuclear protein that undergoes cytoplasmic redistribution and aggregation in the majority of cases of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. TDP-43 autoregulates the abundance of its own transcript TARDBP by binding to an intron in the 3′ untranslated region, although the mechanisms underlying this activity have been debated. Herein, we provide the most extensive analysis of TARDBP transcript yet undertaken. We detail the existence of a plethora of complex splicing events and alternative poly(A) use and provide data that explain the discrepancies reported to date regarding the autoregulatory capacity of TDP-43. Additionally, although many splice isoforms emanating from the TARDBP locus contain the regulated intron in the 3′ UTR, we find only evidence for autoregulation of the transcript encoding full-length TDP-43. Finally, we use a novel cytoplasmic isoform of TDP to induce disease-like loss of soluble, nuclear TDP-43, which results in aberrant splicing and up-regulation of endogenous TARDBP. These results reveal a previously underappreciated complexity to TDP-43 regulated splicing and suggest that loss of TDP-43 autoregulatory capacity may contribute to the pathogenesis of ALS.
Mutations of ribosomal protein S5 suppress a defect in late-30S ribosomal subunit biogenesis caused by lack of the RbfA biogenesis factor
Authors: Nord Stefan , Bhatt Monika J. , Tükenmez Hasan , Farabaugh Philip J. , Wikström P. Mikael
Published: June 2015

The in vivo assembly of ribosomal subunits requires assistance by maturation proteins that are not part of mature ribosomes. One such protein, RbfA, associates with the 30S ribosomal subunits. Loss of RbfA causes cold sensitivity and defects of the 30S subunit biogenesis and its overexpression partially suppresses the dominant cold sensitivity caused by a C23U mutation in the central pseudoknot of 16S rRNA, a structure essential for ribosome function. We have isolated suppressor mutations that restore partially the growth of an RbfA-lacking strain. Most of the strongest suppressor mutations alter one out of three distinct positions in the carboxy-terminal domain of ribosomal protein S5 (S5) in direct contact with helix 1 and helix 2 of the central pseudoknot. Their effect is to increase the translational capacity of the RbfA-lacking strain as evidenced by an increase in polysomes in the suppressed strains. Overexpression of RimP, a protein factor that along with RbfA regulates formation of the ribosome's central pseudoknot, was lethal to the RbfA-lacking strain but not to a wild-type strain and this lethality was suppressed by the alterations in S5. The S5 mutants alter translational fidelity but these changes do not explain consistently their effect on the RbfA-lacking strain. Our genetic results support a role for the region of S5 modified in the suppressors in the formation of the central pseudoknot in 16S rRNA.
Strategies and solutions to alleviate access block and overcrowding in emergency departments
Authors: Chan Stewart SW , Cheung NK , Graham Colin A , Rainer Timothy H
Published: June 2015

Objectives: Access block refers to the delay caused for patients in gaining access to in-patient beds after being admitted. It is almost always associated with emergency department overcrowding. This study aimed to identify evidence-based strategies that can be followed in emergency departments and hospital settings to alleviate the problem of access block and emergency department overcrowding; and to explore the applicability of these solutions in Hong Kong. Data sources: A systematic literature review was performed by searching the following databases: CINAHL, Cochrane Database of Systematic Reviews, EMBASE, MEDLINE (OVID), NHS Evidence, Scopus, and PubMed. Study selection: The search terms used were “emergency department, access block, overcrowding”. The inclusion criteria were full-text articles, studies, economic evaluations, reviews, editorials, and commentaries. The exclusion criteria were studies not based in the emergency departments or hospitals, and abstracts. Data extraction: Abstracts of identified papers were screened, and papers were selected if they contained facts, data, or scientific evidence related to interventions that aimed at improving outcome measures for emergency department overcrowding and/or access block. Papers identified were used to locate further references. Data synthesis: All relevant scientific studies were evaluated for strengths and weaknesses using appraisal tools developed by the Critical Appraisal Skills Programme. We identified solutions broadly classified into the following categories: (1) strategies addressing emergency department overcrowding: co-locating primary care within the emergency department, and fast-track and emergency nurse practitioners; and (2) strategies addressing access block: holding units, early discharge and patient flow, and political action—management and resource priority. Conclusion: Several evidence-based approaches have been identified from the literature and effective strategies to overcome the problem of access block and overcrowding of emergency departments may be formulated.
Analyzing Software as a Service with Per-Transaction Charges
Authors: Ma Dan , Seidmann Abraham
Published: June 2015

Software as a Service (SaaS) delivers a bundle of applications and services through the Web. Its on-demand feature allows users to enjoy full scalability and to handle possible demand fluctuations at no risk. In recent years, SaaS has become an appealing alternative to purchasing, installing, and maintaining modifiable off-the-shelf (MOTS) software packages. We present a game-theoretical model to study the competitive dynamics between the SaaS provider, who charges a variable per-transaction fee, and the traditional MOTS provider. We characterize the equilibrium conditions under which the two coexist in a competitive market and those under which each provider will fail and exit the market. Decreasing the lack-of-fit (or the cross-application data integration) costs of SaaS results in four structural regimes in the market. These are MOTS Dominance → Segmented Market → Competitive Market → SaaS Dominance. Based on our findings, we recommend distinct competitive strategies for each provider. We suggest that the SaaS provider should invest in reducing both its lack-of-fit costs and its per-transaction price so that it can offer increasing economies of scale. The MOTS provider, by contrast, should not resort to a price-cutting strategy; rather, it should enhance software functionality and features to deliver superior value. We further examine this problem from the software life-cycle perspective, with multiple stages over which users can depreciate the fixed costs of installing and customizing their MOTS solutions on site. We then present an analysis that characterizes the competitive outcomes when future technological developments could change the relative levels of the lack-of-fit costs. Specifically, we explain why the SaaS provider will always use a forward-looking pricing strategy: When lack-of-fit costs are expected to decrease (increase) in the future, the SaaS provider should reduce (increase) its current price. This is in contrast with the MOTS provider, who will use the forward-looking pricing strategy only when lack-of-fit costs are expected to increase. Surprisingly, when such costs are expected to decrease, the MOTS provider should ignore this expectation and use the same pricing strategy as in the benchmark with invariant lack-of-fit costs.
How Does IT Ambidexterity Impact Organizational Agility?
Authors: Lee One-Ki (Daniel) , Sambamurthy Vallabh , Lim Kai H. , Wei Kwok Kee
Published: June 2015

Organizational agility is a significant business capability. Though there have been numerous studies about the effects of information technology (IT) capabilities on organizational agility, there has been limited attention on the enabling effects of IT ambidexterity, namely, the dual capacity to explore and exploit IT resources and practices. We propose that IT ambidexterity enhances organizational agility by facilitating operational ambidexterity, and that the magnitude of facilitation depends on the level of environmental dynamism. We test these relationships utilizing data from a large-scale, matched-pair field survey of business and IT executives. The results confirm that a firm’s IT ambidexterity does enhance its organizational agility through the mediated effects of operational ambidexterity, and that the dynamism of a firm’s environment affects these relationships.
Discretionary Sanctions and Rewards in the Repeated Inspection Game
Authors: Nosenzo Daniele , Offerman Theo , Sefton Martin , van der Veen Ailko
Published: June 2015

We experimentally investigate a repeated “inspection game” where, in the stage game, an employee can either work or shirk and an employer simultaneously chooses to inspect or not inspect. The unique equilibrium of the stage game is in mixed strategies with positive probabilities of shirking/inspecting while combined payoffs are maximized when the employee works and the employer does not inspect. We examine the effects of allowing the employer discretion to sanction or reward the employee after observing stage game payoffs. When employers have limited discretion, and can only apply sanctions and/or rewards following an inspection, we find that both instruments are equally effective in reducing shirking and increasing joint earnings. When employers have discretion to reward and/or sanction independently of whether they inspect, we find that rewards are more effective than sanctions. In treatments where employers can combine sanctions and rewards, employers rely mainly on rewards, and outcomes closely resemble those of treatments where only rewards are possible.

Data, as supplemental material, are available at http://dx.doi.org/10.1287/mnsc.2014.2124 .

This paper was accepted by John List, behavioral economics.
Research Roundup
Authors: McLoughlin Alison
Published: June 2015

Alison McLoughlin provides a synopsis and brief review of a selection of recently published research articles of interest to neuroscience nurses, highlighting the key points to keep you up to date. A full reference is provided for those who wish to read the research in more detail.
Validating the inter-rater reliability of an anorectal assessment tool
Authors: Evans Patricia , Collins Brigitte , O'Brien Lorraine , Bradshaw Elissa , Swatton Anna , Norton Christine
Published: June 2015

Background

To date, there has been no validated assessment tool or rating scale for recording the results of a digital rectal examination. A scale, similar to that used for vaginal examination, was developed for anorectal examination.

Aim

The study aimed to establish inter-rater reliability of the anorectal assessment tool.

Method

Consenting patients with symptoms of constipation or faecal incontinence were examined by two clinicians in random order. Both clinicians were blinded to the other's findings. Agreement to within one point was expected on 0–5 scales for examination and 90% agreement and above on categorical observations.

Results

A total of 98 patients participated in this study. The study's findings indicate that experienced clinicians interpret the results of the anorectal assessment in a reasonably similar, but not identical, manner.

Conclusion

This tool can be useful in clinical and research settings. Future work is needed to refine the tool and to test it in a variety of settings.
Community hepatitis C treatment in Cornwall: a model to improve care
Authors: Hampton Helen , Farrington ElizabethS , Ellery Adam , McKenna Mary , Stableforth William , Hussaini Hyder
Published: June 2015

Many people who inject drugs (PWID) who are infected with chronic hepatitis C virus (HCV) cannot engage with secondary care services due to social and geographical difficulties. The Cornish HCV management model integrates hospital-based hepatology and community drug and alcohol services, such as Addaction. Community blood-borne virus (BBV) screening is performed by Addaction staff. BBV nurses discuss results with patients. Results are reviewed at multidisciplinary meetings with the hepatology secondary care team with regard to a management plan. Patients were then treated either in the community by a BBV nurse or in secondary care. The community-based treatment of 43 HCV-positive PWID (2008–2012) resulted in a sustained virological response rate of 72% across genotypes 1–3 with only a 5% failure to complete therapy. This integrated model can help to increase HCV treatment rates in Cornwall and provide a national model for HCV treatment, particularly in non-urban areas.
Cognitive dysfunction in older dogs and cats: the role of the veterinary nurse in screening
Authors: Fry Margaret
Published: June 2015

Cognitive dysfunction is a progressive neurodegenerative disorder. It affects 14.2% of older dogs over 8 years of age. In cats, 28% aged 11 to 14 years develop one geriatric-onset behaviour problem. This increases to over 50% in cats 15 years of age and older. Detection of cognitive dysfunction in cats and dogs is by observation of clinical behavioural signs, often thought to be a normal part of ageing. Early recognition is crucial. Signs detected early are treatable or temporarily reversible.

This literature review focused on areas the veterinary nurse could influence in practice such as detection of behavioural signs and advice on diet, behaviour management and enrichment.

Results showed dietary and nutritional supplements as well as behavioural and environmental enrichment alongside medication can slow progression of cognitive dysfunction predominately in dogs. Regular screening of older pets and education of owners by veterinary nurses can help with early detection and referral to a veterinary surgeon. Future research should focus on further development of standardised, validated screening tools and management protocols.
EHR-based Visualization Tool: Adoption Rates, Satisfaction, and Patient
Outcomes
Authors: Foraker Randi E. , Kite Bobbie , Kelley Marjorie , Lai Albert M. , Roth Caryn , Lopetegui Marcelo A. , Shoben Abigail B. , Langan Michael , Rutledge Nicole , Payne Philip R.O.
Published: June 2015

Background: Electronic health records (EHRs) have the potential to enhance
patient-provider communication and improve patient outcomes. However, in order to impact
patient care, clinical decision support (CDS) and communication tools targeting such
needs must be integrated into clinical workflow and be flexible with regard to the
changing health care landscape.Design: The Stroke Prevention in Healthcare Delivery
Environments (SPHERE) team developed and implemented the SPHERE tool, an EHR-based CDS
visualization, to enhance patient-provider communication around cardiovascular health
(CVH) within an outpatient primary care setting of a large academic medical
center.Implementation: We describe our successful CDS alert implementation strategy and
report adoption rates. We also present results of a provider satisfaction survey showing
that the SPHERE tool delivers appropriate content in a timely manner. Patient outcomes
following implementation of the tool indicate one-year improvements in some CVH metrics,
such as body mass index and diabetes.Discussion: Clinical decision-making and practices
change rapidly and in parallel to simultaneous changes in the health care landscape and
EHR usage. Based on these observations and our preliminary results, we have found that
an integrated, extensible, and workflow-aware CDS tool is critical to enhancing
patient-provider communications and influencing patient outcomes.
Los principios implícitos. Su relevancia en la aplicación del Derecho
Authors: Alonso Vidal Horacio José
Published: June 2015

El trabajo analiza la importancia en la aplicación del derecho de los principios implícitos. El primer apartado, consiste en un análisis estructural y como razones para la acción de los principios implícitos. El segundo apartado, aborda la cuestión sobre si la aplicación de los principios implícitos supone un ejercicio de discrecionalidad por el órgano de aplicación del derecho o no. Finalmente, a modo de conclusión, el autor sostiene que, pese a su indudable interés teórico, los principios implícitos tienen una relevancia menor en la aplicación cotidiana del derecho, excepto en aquellos supuestos en los que se haga una interpretación novedosa del mismo.
La expansión de la hermenéutica filosófica en el Derecho
Authors: Streck Lenio Luiz
Published: June 2015

El giro hermenéutico-ontológico que se produjo en el siglo xx proporcionó un nuevo enfoque de la hermenéutica, ahora filosófica. A lo largo de este giro radical, podemos ver tres fases, a saber: la hermenéutica como una técnica especial de interpretación (hermenéutica especial), como una teoría general de la interpretación y como hermenéutica fundamental. Sin embargo, aún con todos los cambios que se producen dentro de una teoría crítica, con la superación de la hermenéutica clásica, todavía hay una gran resistencia a aceptar la recepción de la Hermenéutica Filosófica por el derecho de los campos tradicionales de pensamiento jurídico contemporáneo.