bluuebunny/crossref_metadata_2025 huggingface dataset:
A Contingency Approach on the Impact of Front-End Success on Project Portfolio Success
Authors: Kock Alexander , Heising Wilderich , Gemünden Hans Georg
Published: March 2016

The pre-project or ideation phase is often disregarded in project portfolio management. Senior managers put more emphasis on later project stages, and researchers predominantly investigate the front end from a single project perspective. This study investigates how and under which circumstances the performance of the front end affects project portfolio success. Using a sample of 175 firms, we confirm a strong positive relationship between front-end success and project portfolio success. Results show that this effect becomes stronger for larger project portfolios, for portfolios with more interdependency between projects and, finally, for firms that have a strategic orientation toward riskiness.
Deguelin‐induced blockade of PI3K/protein kinase B/MAP kinase signaling in zebrafish and breast cancer cell lines is mediated by down‐regulation of fibroblast growth factor receptor 4 activity
Authors: Wu Wei , Hai Yang , Chen Lu , Liu Rui‐Jin , Han Yu‐Xiang , Li Wen‐Hao , Li Song , Lin Shuo , Wu Xin‐Rong
Published: March 2016

Deguelin, a natural component derived from leguminous plants, has been used as pesticide in some regions. Accumulating evidence show that deguelin has promising chemopreventive and therapeutic activities against cancer cells. This study shows that low concentrations of deguelin can lead to significant delay in zebrafish embryonic development through growth inhibition and induction of apoptosis. Furthermore, we identified fibroblast growth factor receptor 4 (FGFR4) as the putative target of deguelin. The candidate was initially identified by a microarray approach and then validated through in vitro experiments using hormone‐responsive (MCF‐7) and nonresponsive (MDA‐MB‐231) human breast cancer cell lines. The results show that deguelin suppressed cell proliferation and induced apoptosis in both cancer cell lines, but not in Hs 578Bst cells, by blocking PI3K/AKT and mitogen‐activated protein kinases (MAPK) signaling. The FGFR4 mRNA and protein level also diminished in a dose‐dependent manner. Interestingly, we found that forced FGFR4 overexpression attenuated deguelin‐induced proliferative suppression and apoptotic cell death in both zebrafish and MCF‐7 cell lines, p‐AKT and p‐ERK levels were restored upon FGFR4 overexpression. Taken together, our results strongly suggest that deguelin inhibition of PI3K/AKT and MAPK signaling in zebrafish and breast cancer cell lines is partially mediated through down‐regulation of FGFR4 activity.
Comparative effects of immediate‐release and extended‐release aspirin on basal and bradykinin‐stimulated excretion of thromboxane and prostacyclin metabolites
Authors: Gamboa Jorge L. , Devin Jessica K. , Ramirez Claudia E. , Yu Chang , Nian Hui , Lee Rhonda H. , Brown Nancy J.
Published: March 2016

A goal of aspirin therapy is to inhibit thromboxane production and platelet aggregation without inhibiting endothelial production of the vasodilator and anti‐thrombotic prostacyclin. This study tested the hypothesis that extended‐release aspirin (NHP‐554C) would have increased selectivity for inhibition of basal and simulated thromboxane formation compared to immediate‐release aspirin (ASA). Thirty‐six healthy subjects were randomized to NHP‐554C or ASA groups. Within each group, subjects were randomized to 5‐day treatment with 81 mg/d, 162.5 mg/d and placebo in a crossover design in which treatment periods were separated by 2‐week washout. On the fifth day of treatment, 81 mg/d and 162.5 mg/d ASA reduced basal urinary excretion of the stable thromboxane metabolite 11‐dehydro‐thromboxane B2 62.3% and 66.2% and basal excretion of the stable prostacyclin metabolite 2,3‐dinor‐6‐keto‐PGF1α 22.8% and 26.5%, respectively, compared to placebo. NHP‐554C 81 mg/d and 162.5 mg/d reduced 11‐dehydro‐thromboxane B2 53% (P = 0.03 vs. ASA 81 mg/d) and 67.9% and 2,3‐dinor‐6‐keto‐PGF1α 13.4% and 18.5%, respectively. NHP‐554C 81 mg/d did not significantly reduce basal excretion of the prostacyclin metabolite. Both doses of ASA and NHP significantly reduced excretion of both thromboxane and prostacyclin metabolites following intravenous bradykinin. During NHP‐554C 162.5 mg/d, but not during ASA, bradykinin significantly increased urinary 2,3‐dinor‐6‐keto‐PGF1α. Nevertheless, 11‐dehydro‐thromboxane B2 and 2,3‐dinor‐6‐keto‐PGF1α responses to bradykinin were statistically similar during ASA and NHP‐554C. In conclusion, at doses of 81 and 162.5 mg/d immediate‐ and extended‐release aspirin selectively decrease basal thromboxane production. Both forms of aspirin decrease bradykinin‐stimulated thromboxane and prostacyclin production, but some stimulated prostacyclin production remains during treatment with NHP‐554C.
Performance of ultra‐thin HfO2‐based MIM devices after oxygen modulation and post‐metallization annealing in N2
Authors: Molina Joel , Thamankar Ramesh , Pey Kin Leong
Published: March 2016

In this work, we discuss the electrical characteristics of metal–insulator–metal (MIM) structures based on ultra‐thin hafnium oxides whose stoichiometry have been modified and a thermal treatment after gate metallization has also been applied. Here, we show that the current–voltage characteristics are improved for the annealed samples in terms of lower gate leakage current densities and higher breakdown electric fields. In addition, the role of the modulation in the oxygen concentration for HfO2 on the MIM's current–voltage, capacitance–voltage, and resistive switching characteristics is also addressed. From these data, a trade‐off between current–voltage characteristics and basic memory performance is clearly seen, thus highlighting the importance of combining oxygen modulation and/or post‐metallization annealing in HfO2‐based MIM structures. Finally, the resistive switching effect is shown in the bipolar mode for some MIM structures and the dominant carrier conduction mechanism (just before the SET condition) is also obtained and related to Poole–Frenkel conduction.
4-Aminopyridine Induced Activity Rescues Hypoexcitable Motor Neurons from Amyotrophic Lateral Sclerosis Patient-Derived Induced Pluripotent Stem Cells
Authors: Naujock Maximilian , Stanslowsky Nancy , Bufler Sebastian , Naumann Marcel , Reinhardt Peter , Sterneckert Jared , Kefalakes Ekaterini , Kassebaum Carola , Bursch Franziska , Lojewski Xenia , Storch Alexander , Frickenhaus Marie , Boeckers Tobias M. , Putz Stefan , Demestre Maria , Liebau Stefan , Klingenstein Moritz , Ludolph Albert C. , Dengler Reinhard , Kim Kwang-Soo , Hermann Andreas , Wegner Florian , Petri Susanne
Published: March 2016

Despite decades of research on amyotrophic lateral sclerosis (ALS), there is only one approved drug, which minimally extends patient survival. Here, we investigated pathophysiological mechanisms underlying ALS using motor neurons (MNs) differentiated from induced pluripotent stem cells (iPSCs) derived from ALS patients carrying mutations in FUS or SOD1. Patient-derived MNs were less active and excitable compared to healthy controls, due to reduced Na+/K+ ratios in both ALS groups accompanied by elevated potassium channel (FUS) and attenuated sodium channel expression levels (FUS, SOD1). ALS iPSC-derived MNs showed elevated endoplasmic reticulum stress (ER) levels and increased caspase activation. Treatment with the FDA approved drug 4-Aminopyridine (4AP) restored ion-channel imbalances, increased neuronal activity levels and decreased ER stress and caspase activation. This study provides novel pathophysiological data, including a mechanistic explanation for the observed hypoexcitability in patient-derived MNs and a new therapeutic strategy to provide neuroprotection in MNs affected by ALS.
Immunolocalisation of aromatase regulators liver kinase B1, phosphorylated AMP-activated protein kinase and cAMP response element-binding protein-regulated transcription co-activators in the human testis
Authors: Ham Seungmin , Brown Kristy A. , Simpson Evan R. , Meachem Sarah J.
Published: March 2016

Although oestrogens are essential for spermatogenesis and their biosynthesis is dependent on aromatase expression, the molecular mechanism of aromatase regulation is poorly understood. Our laboratory has demonstrated that liver kinase B1 (LKB1) is a negative regulator of aromatase in the breast by phosphorylating AMP-activated protein kinase (AMPK) and inhibiting the nuclear translocation of the cAMP response element-binding protein-regulated transcription co-activator (CRTC) 2. The aim of this study was to determine the location of testis-associated proteins in the LKB1–CRTC pathway. Aromatase, LKB1, phosphorylated AMPK (pAMPK) and CRTC1–3 were examined by selected immunofluorescent antibodies in testis samples from a prepubertal boy and three fertile men. Aromatase, pAMPK and LKB1 proteins were present in the seminiferous epithelium and interstitium of the testis and were expressed in a differential and developmental manner in particular cell types. The expression pattern of LKB1 was similar to that of pAMPK and inversely related to aromatase expression. CRTC1 and CRTC3 were localised in the seminiferous epithelium, whereas CRTC2 was barely detectable in testis. These results lead to the conclusion that LKB1 is involved in the molecular pathway that underpins aromatase regulation in the testis via CRTC1 and CRTC3 and may be important for the oestrogen-mediated development of germ cells.
Model Coupling in Resource Economics: Conditions for Effective Interdisciplinary Collaboration
Authors: MacLeod Miles , Nagatsu Michiru
Published: March 2016

In this article we argue for the importance of studying interdisciplinary collaborations by focusing on the role that good choice and design of model-building frameworks and strategies can play overcoming the inherent difficulties of collaborative research. We provide an empirical study of particular collaborations between economists and ecologists in resource economics. We discuss various features of how models are put together for interdisciplinary collaboration in these cases and show how the use of a coupled-model framework in this case to coordinate and combine background models from ecology and economics provided particular collaborative affordances and clear collaborative gain.
Superficial CD34‐positive fibroblastic tumor: A new case from Japan
Authors: Wada Naoko , Ito Takamichi , Uchi Hiroshi , Nakahara Takeshi , Tsuji Gaku , Yamada Yuichi , Oda Yoshinao , Furue Masutaka
Published: March 2016

A 48‐year‐old Japanese woman presented with a painless, slow‐growing, brown nodule of 15 mm in diameter on the left thigh. She noticed the nodule a few years before the first presentation to our hospital. She underwent total resection of the nodule. On histopathological examination, a relatively well‐defined tumor with infiltrative growth was located in the dermis and extended into the subcutis. The tumor was composed of spindle to polygonal cells with pleomorphic nuclei arranged in a sheet‐like or fascicular pattern. Tumor cells with granular cytoplasm were also scattered. Immunohistochemical examination revealed that the tumor cells were strongly positive for CD34. The fusion transcripts of the collagen type 1 alpha 1 platelet‐derived growth factor beta chain were not detected. After excluding other fibroblastic tumors through histopathological and immunohistochemical examinations, a diagnosis of superficial CD34‐positive fibroblastic tumor (SCPFT) was made. SCPFT is a recently proposed fibroblastic tumor that is characterized by striking pleomorphism, granular cytoplasm, low mitotic rate and diffuse CD34 expression. Only two reports with 20 cases have been reported so far. The present case is the first that corresponds to SCPFT in Japan.
Health Ombudsmen in Polycentric Regulatory Fields: England, New Zealand, and Australia
Authors: Healy Judith , Walton Merrilyn
Published: March 2016

Health ombudsmen (health complaints commissioners), an unusual entity internationally, exist only in England, New Zealand, and the Australian states and territories. Established to respond to complaints from patients, the intention is to make health services and professionals more accountable to the public. Most cases are handled around the softer base of a regulatory pyramid, such as advice to complainants and requests to providers for an explanation and/or apology. Few cases escalate to investigations and prosecutions. Although the legal powers of some health ombudsmen to redress individual grievances have been strengthened, most lack the independent power to initiate an inquiry into systemic problems. To produce quality improvements, health ombudsmen need powers to require compliance from providers and to initiate inquiries. With the advent of new health sector regulators, health ombudsmen must negotiate their role and function within expanding networks of governance.
Time trends in alcohol intake in early pregnancy and official recommendations in Denmark, 1998–2013
Authors: Kesmodel Ulrik S. , Petersen Gitte L. , Henriksen Tine B. , Strandberg‐Larsen Katrine
Published: March 2016

Introduction

In 1999, Danish health authorities modified their recommendation to pregnant women, condoning some alcohol intake. In 2007, the recommendation was changed to one of alcohol abstention. We aimed to assess changes in average alcohol intake (drinks/week) and alcohol binge drinking in early pregnancy from 1998 to 2013 in relation to the changes in official recommendations in 1999 (condoning some intake) and 2007 (abstention).

Material and methods

All Danish‐speaking pregnant women attending routine antenatal care at the Department of Obstetrics and Gynecology, Aarhus University Hospital, Denmark, between September 1998 and June 2013 were invited to participate. During the study period, 68 395 pregnant women filled in a self‐administered questionnaire at gestational week 11 (median). From 1998, questions on binge drinking included data on the number of binge episodes (≥5 drinks on a single occasion), and the timing (gestational week) of these episodes. Additional questions on binge drinking defined as ≥3 drinks on a single occasion were asked separately from 2000. A question assessed the average number of alcohol‐containing drinks per week the woman consumed currently at the time of filling in the questionnaire.

Results

From 1998 to 2013 the proportion of women reporting no alcohol intake increased from 31.2 to 83.3% (p < 0.001), the main decline occurring between 1998 and 2007. The proportion of binge drinkers decreased (p < 0.001) but remained more stable across the period.

Conclusions

The decline in the proportion of pregnant women consuming alcohol occurred independently of official recommendations. Increasing national and international awareness may partly explain the changes.
Incidence of apparent life‐threatening events and post‐neonatal risk factors
Authors: Monti Maria Cristina , Borrelli Paola , Nosetti Luana , Tajè Silvia , Perotti Milena , Bonarrigo Domenico , Stramba Badiale Marco , Montomoli Cristina
Published: March 2016

Aim

Even though a standard clinical definition for an apparent life‐threatening event (ALTE) was established more than two decades ago, the specific International Classification of Disease (ICD) code was firstly included only in 2012. This study estimated the incidence of ALTEs in Northern Italy, together with features and risk factors.

Methods

We used the Lombardy Region Hospital Discharge Records (HDR) database to estimate the cumulative incidence for ALTE during 2002–2006 and drew up a risk profile by comparing cases with and without ALTE who were followed in infancy.

Results

There were 246 infants registered in the HDR with ALTE putative diagnostic codes, suggesting a cumulative incidence of 4.1 per 1000 live births in the study area. Of the 148 cases with clinical co‐morbidities, 31% had gastroesophageal reflux and 7% had acute respiratory infections. We analysed follow‐up data from 15 ALTE cases and 1619 healthy infants and found that the significant risk factors were gastroesophageal reflux and a family history of sudden death.

Conclusion

We established the regional incidence of ALTE and found risk factors in infants considered healthy in the first week of life and without pathological perinatal conditions. The systematic use of the specific ALTE ICD code (R68.13, ICD‐10‐CM) and common knowledge about ALTE diagnostic guidelines are clearly needed.
Efficacy and safety of prophylactic levetiracetam in supratentorial brain tumour surgery: a systematic review and meta‐analysis
Authors: Pourzitaki Chryssa , Tsaousi Georgia , Apostolidou Eirini , Karakoulas Konstantinos , Kouvelas Dimitrios , Amaniti Ekaterini
Published: March 2016

Aims

The aim of this study was to perform an up‐to‐date systematic review and meta‐analysis on the efficacy and safety of prophylactic administration of levetiracetam in brain tumour patients.

Method

A systematic review of studies published until April 2015 was conducted using Scopus/Elsevier, EMBASE and MEDLINE. The search was limited to articles reporting results from adult patients, suffering from brain tumour, undergoing supratentorial craniotomy for tumour resection or biopsy and administered levetiracetam in the perioperative period for seizure prophylaxis. Outcomes included the efficacy and safety of levetiracetam, as well as the tolerability of the specific regimen, defined by the discontinuation of the treatment due to side effects.

Results

The systematic review included 1148 patients from 12 studies comparing levetiracetam with no treatment, phenytoin and valproate, while only 243 patients from three studies, comparing levetiracetam vs phenytoin efficacy and safety, were included in the meta‐analysis. The combined results from the meta‐analysis showed that levetiracetam administration was followed by significantly fewer seizures than treatment with phenytoin (OR = 0.12 [0.03–0.42]: χ2 = 1.76: I2 = 0%). Analysis also showed significantly fewer side effects in patients receiving levetiracetam, compared to other groups (P < 0.05). The combined results showed fewer side effects in the levetiracetam group compared to the phenytoin group (OR = 0.65 [0.14–2.99]: χ2 = 8.79: I2 = 77%).

Conclusions

The efficacy of prophylaxis with levetiracetam seems to be superior to that with phenytoin and valproate administration. Moreover, levetiracetam use demonstrates fewer side effects in brain tumour patients. Nevertheless, high risk of bias and moderate methodological quality must be taken into account when considering these results.
Comment on Non‐unique stratal geometries: implications for sequence stratigraphic interpretations, by: P.M. Burgess and G.D. Prince,Basin Research(2015) 27, 351–365
Authors: Catuneanu Octavian , Zecchin Massimo
Published: March 2016

The non‐unique variability highlighted by Burgess & Prince (Basin Res. 2015,27, 351) (i.e. the origin and timing of maximum flooding surfaces, maximum regressive surfaces and subaerial unconformities; the process of topset aggradation in relation with the various types of shoreline trajectory; and the multiple controls that may affect the progradation and retrogradation of a shoreline) is irrelevant to the workflow of sequence stratigraphy. What is relevant is the observation of the unique stratal geometries that are diagnostic to the definition of all units and surfaces of sequence stratigraphy. In downstream‐controlled settings, these unique stratal stacking patterns relate to the forced regressive, normal regressive and transgressive shoreline trajectories. Multiple controls interplay during the formation of each type of stacking pattern, including accommodation, sediment supply and the energy of the sediment‐transport agents. This interplay explains the non‐unique variability, but does not change the unique criteria that afford a consistent application of sequence stratigraphy. Failure to rationalize the non‐unique variability within the context of unique stratal geometries is counterproductive, and obscures the simple workflow of sequence stratigraphy.
Visual outcomes with femtosecond laser‐assisted cataract surgery versus conventional cataract surgery in toric IOL insertion
Authors: Oakley Carmen L , Ewe Shaun Y , Allen Penelope L , Vote Brendan J
Published: March 2016

Background

To evaluate the visual outcomes of femtosecond laser‐assisted cataract surgery (LCS) compared with phacoemulsification cataract surgery (PCS) in patients undergoing Toric IOL insertion.

Design

A non‐randomized, single surgeon, prospective, comparative cohort case series

Participants

Patients undergoing LCS and PCS between January 2012 and July 2014 at a single center.

Methods

The LCS group underwent femtosecond laser pretreatment for the anterior capsulotomy and lens fragmentation. Otherwise standard phacoemulsification surgery and foldable toric intraocular lens insertion proceeded.

Main Outcome Measures

Best corrected visual acuity (BCVA), uncorrected visual acuity (UCVA), pre and post operative cylinder and mean absolute refractive error.

Results

A total of 418 eyes from 323 patients were included in the study; with 95 eyes in the PCS group and 323 in the LCS group. There were 243 (75.5%) LCS eyes with a pre‐operative BCVA of 20/40 or better and 54 (56.8%) in the PCS group (p < 0.001). For post‐operative BCVA, 315 (97.5 %) LCS and 81 (85.3%) PCS eyes had a BCVA of 20/40 or better (p = <0.001). However, there was no significant difference for change in BCVA between the groups (mean gain in EDTRS letter 11.0 for LCS and 10.3 for PCS p = 0.64) or in MAE (mean 0.56D PCS vs 0.65D LCS p = 0.18).

Conclusion

In patients receiving toric intraocular lenses, there is similar improvement in terms of letters gained with LCS and PCS. Overall, there is no additional benefit for patients undergoing LCS in this cohort.
Tranexamic acid in epistaxis: a systematic review
Authors: Kamhieh Y. , Fox H.
Published: March 2016

Background

The role of tranexamic acid in the management of epistaxis remains unclear. There is uncertainty about its safety and about the contraindications for its use. We performed a systematic review of the use of systemic and topical tranexamic acid in epistaxis and a comparative review of its use in other specialties.

Objective of review

This review assesses and summarises the existing evidence for the efficacy and safety of tranexamic acid in the management of epistaxis.

Type of review

Systematic review.

Search strategy

MEDLINE and EMBASE were searched for ‘epistaxis’ and equivalent MESH terms, combined with the Boolean operator ‘OR’ and ‘tranexamic acid’. The Cochrane library and society guidelines were reviewed for evidence regarding the use of tranexamic acid in other specialties.

Evaluation method

All five relevant RCTs were included in the review and were evaluated according to the recommendations of the Cochrane Handbook for Systematic Reviews.

Results

Three RCTS pertained to spontaneous epistaxis; of these, one trial found no benefit of oral tranexamic acid in acute epistaxis, one trial found no significant benefit of topical tranexamic acid, but the largest of the trials showed significant benefit of topical tranexamic acid in acute epistaxis management. Two RCTs examined oral tranexamic acid for prophylaxis of recurrent epistaxes in patients with hereditary haemorrhagic telangiectasia; both showed significant reduction in severity and frequency.

Conclusions

Tranexamic acid, as a WHO ‘essential medicine’, is a powerful, readily available tool, the use of which in epistaxis has been limited by uncertainty over its efficacy and its safety profile. This systematic review summarises the existing evidence and extrapolates from the wealth of data for other specialties to address the clinical question – does TXA have a role in epistaxis management?
When Absence of Evidence Is Evidence of Absence: Rational Inferences From Absent Data
Authors: Hsu Anne S. , Horng Andy , Griffiths Thomas L. , Chater Nick
Published: March 2016

Identifying patterns in the world requires noticing not only unusual occurrences, but also unusual absences. We examined how people learn from absences, manipulating the extent to which an absence is expected. People can make two types of inferences from the absence of an event: either the event is possible but has not yet occurred, or the event never occurs. A rational analysis using Bayesian inference predicts that inferences from absent data should depend on how much the absence is expected to occur, with less probable absences being more salient. We tested this prediction in two experiments in which we elicited people's judgments about patterns in the data as a function of absence salience. We found that people were able to decide that absences either were mere coincidences or were indicative of a significant pattern in the data in a manner that was consistent with predictions of a simple Bayesian model.
Case of Barrett's adenocarcinoma with marked endoscopic morphological changes in Barrett's esophagus over a long follow‐up period of 15 years
Authors: Iwaya Yugo , Yamazaki Tomoo , Watanabe Takayuki , Seki Ayako , Ochi Yasuhide , Hara Etsuo , Arakura Norikazu , Tanaka Eiji , Hasebe Osamu
Published: March 2016

The natural history of Barrett's esophagus (BE) is unclear. We herein describe a case of Barrett's adenocarcinoma (BAC) in which we could closely observe marked morphological changes in BE over a long follow‐up period of 15 years. A man in his seventies received routine esophagogastroduodenoscopy (EGD) and was diagnosed as having reflux esophagitis and short‐segment BE. The BE gradually became elongated, and BAC was detected 9 years following the initial EGD examination with continued administration of a proton pump inhibitor. We witnessed that BE elongated sporadically over time and mucosal breaks of reflux esophagitis were detectable several years before elongation. The patient underwent endoscopic submucosal dissection for BAC and has been monitored by EGD every year thereafter. These remarkable morphological changes may be representative of the natural history of BE and aid in deciding long‐term disease management.
The importance of understanding gait features in hereditary spastic paraplegia: accomplishments and next steps
Authors: Ounpuu Sylvia
Published: March 2016

This commentary is on the original article by Adair et al. on pages 829–835 of this issue.
How do we ensure sustainable physical activity options for people with disabilities?
Authors: Wiart Lesley
Published: March 2016

This commentary is on the review by Verschuren et al. on pages 798–808 of this issue.
Forest understory plant and soil microbial response to an experimentally induced drought and heat‐pulse event: the importance of maintaining the continuum
Authors: von Rein Isabell , Gessler Arthur , Premke Katrin , Keitel Claudia , Ulrich Andreas , Kayler Zachary E.
Published: March 2016

Drought duration and intensity are expected to increase with global climate change. How changes in water availability and temperature affect the combined plant–soil–microorganism response remains uncertain. We excavated soil monoliths from a beech (Fagus sylvatica L.) forest, thus keeping the understory plant–microbe communities intact, imposed an extreme climate event, consisting of drought and/or a single heat‐pulse event, and followed microbial community dynamics over a time period of 28 days. During the treatment, we labeled the canopy with 13CO2 with the goal of (i) determining the strength of plant–microbe carbon linkages under control, drought, heat and heat–drought treatments and (ii) characterizing microbial groups that are tightly linked to the plant–soil carbon continuum based on 13C‐labeled PLFAs. Additionally, we used 16S rRNA sequencing of bacteria from the Ah horizon to determine the short‐term changes in the active microbial community. The treatments did not sever within‐plant transport over the experiment, and carbon sinks belowground were still active. Based on the relative distribution of labeled carbon to roots and microbial PLFAs, we determined that soil microbes appear to have a stronger carbon sink strength during environmental stress. High‐throughput sequencing of the 16S rRNA revealed multiple trajectories in microbial community shifts within the different treatments. Heat in combination with drought had a clear negative effect on microbial diversity and resulted in a distinct shift in the microbial community structure that also corresponded to the lowest level of label found in the PLFAs. Hence, the strongest changes in microbial abundances occurred in the heat–drought treatment where plants were most severely affected. Our study suggests that many of the shifts in the microbial communities that we might expect from extreme environmental stress will result from the plant–soil–microbial dynamics rather than from direct effects of drought and heat on soil microbes alone.
Understanding hotspots within a global hotspot – identifying the drivers of regional species richness patterns in terrestrial subterranean habitats
Authors: Bregović Petra , Zagmajster Maja
Published: March 2016

We tested three hypotheses (productive energy, habitat heterogeneity, historical climate stability) to explain regional species richness patterns in subterranean habitats, which have less habitat/climatic variability than surface habitats.

For the first time, we investigated the pattern of two species richness hotspots in the world's richest region in subterranean biodiversity in southeast Europe. We used distribution records for 388 species of beetles, the most species rich group of terrestrial subterranean fauna, belonging to subfamilies Trechinae (Carabidae) and Leptodirinae (Cholevidae), and mapped them onto a 20 × 20 km grid.

We applied spatial and non‐spatial multiple regression, using generalised linear models and spatial eigenvector mapping. The relative importance of each hypothesis, and of the spatial versus the environmental components, was assessed with variation partitioning. We analysed the total dataset as well as each subfamily separately.

Our results show that although the relative importance of species richness drivers differed among taxonomic groups, in most cases habitat heterogeneity had the biggest influence. It was followed by historical climate stability, while productive energy had a neglecting effect. This proves that even though habitat variability is smaller in subterranean than in surface habitats, its gradient is still strong enough to explain species richness patterns better than the other two hypotheses.

Identification of the drivers shaping the two regional species richness hotspots within a global hotspot of highly endemic subterranean fauna is important for conservation practices. Additionally, we contribute to the general understanding of species richness patterns of insects, by providing the first detailed analyses on a regional scale for subterranean systems.
How and when should flightless, saproxylic, litter‐dwelling coleoptera be surveyed?
Authors: Cateau Eugénie , Courtin Olivier , Brustel Hervé
Published: March 2016

The limited dispersal and the high trophic requirements of flightless saproxylic beetles makes them good indicators of spatial and temporal continuity. Few studies have been conducted on these species, and the two main studies produced contradictory results. Knowledge is thus lacking on this fauna, but before performing experiments to assess their value as indicators, it is important to know how and when they can be sampled.

Sieving litter and Berlese extraction in six oak woodlands showed that sampling 10 trees per forest is sufficient to capture 97.2% of the fauna present.

Two stands were surveyed at monthly intervals for 2 years to determine the species phenology. All the species were present throughout the year. Variation in abundance was only observed in four out of 11 species. Spring and fall were shown to be the best periods to survey them in the litter. No significant variation in abundance was observed between the two sampling years. This fauna thus appears to be very stable over time.

Certain climate parameters, high humidity (little sunshine and rainfall several days before sampling) may result in the beetles being more abundant in the litter at certain times. For efficient sampling, long periods of fine weather should thus be avoided.
Disseminated anetoderma in a patient with nodal Epstein–Barr virus‐associated classical Hodgkin lymphoma: Anetodermic form of a concurrent discordant cutaneous marginal zone lymphoma
Authors: Varshney Anupam , Goyal Tarang , Zawar Vijay , Tinguely Marianne , Kempf Werner
Published: March 2016

Patients with a lymphoma have an increased risk of developing a second lymphoproliferative disorder. The association of nodal Hodgkin lymphoma and primary cutaneous marginal zone lymphoma (MALT type) is exceptional, and only very few cases have been documented. Anetoderma represents a circumscribed loss or rarefication of elastic fibers. Different underlying processes may result in anetoderma, including cutaneous marginal zone lymphoma. We report a 50‐year‐old male patient with Epstein–Barr virus (EBV)‐associated nodal Hodgkin lymphoma who presented with disseminated anetodermic skin lesions. Biopsies of the skin lesions revealed a B‐cell infiltrate containing monoclonal plasma cells but without detection of EBV. The skin lesions represent an anetodermic form of primary cutaneous marginal zone lymphoma. It is the first case report of an association of anetodermic cutaneous marginal zone lymphoma and a synchronous EBV‐associated nodal Hodgkin lymphoma.
Susceptibility of swine to H5 and H7 low pathogenic avian influenza viruses
Authors: Balzli Charles , Lager Kelly , Vincent Amy , Gauger Phillip , Brockmeier Susan , Miller Laura , Richt Juergen A , Ma Wenjun , Suarez David , Swayne David E
Published: March 2016

Background

The ability of pigs to become infected with low pathogenic avian influenza (LPAI) viruses and then generate mammalian adaptable influenza A viruses is difficult to determine. Yet, it is an important link to understanding any relationship between LPAI virus ecology and possible epidemics among swine and/or humans.

Objectives

Assess susceptibility of pigs to LPAI viruses found within the United States and their direct contact transmission potential.

Methods

Pigs were inoculated with one of ten H5 or H7 LPAI viruses selected from seven different bird species to test infectivity, virulence, pathogenesis, and potential to transmit virus to contact pigs through histological, RRT‐PCR and seroconversion data.

Results

Although pigs were susceptible to infection with each of the LPAI viruses, no clinical disease was recognized in any pig. During the acute phase of the infection, minor pulmonary lesions were found in some pigs and one or more pigs in each group were RRT‐PCR‐positive in the lower respiratory tract, but no virus was detected in upper respiratory tract (negative nasal swabs). Except for one group, one or more pigs in each LPAI group developed antibody. No LPAI viruses transmitted to contact pigs.

Conclusions

LPAI strains from various bird populations within the United States are capable of infecting pigs. Although adaptability and transmission of individual strains seem unlikely, the subclinical nature of the infections demonstrates the need to improve sampling and testing methods to more accurately measure incidence of LPAI virus infection in pigs, and their potential role in human‐zoonotic LPAI virus dynamics.
… and justice for all?: Basic income and the principles of gender equity
Authors: McLean Caitlin
Published: March 2016

Nowhere have basic income proposals been more hotly debated than among feminists. Perhaps it is ironic, then, argues Caitlin McLean, that a basic income has the potential to overcome deep divisions by satisfying core principles of gender equity, as well as improving the position of women in all their diversity.
Rescuing responsibility for the left: An egalitarian account of social security and obligation
Authors: McTernan Emily
Published: March 2016

Without a convincing account of inequality's causes, egalitarians will continue to cede ground to the right, whose language of prudence and responsibility justifies further tightening of the welfare system. Advancing the cause of equality requires engaging with the right on the terrain of ideas and values, argues Emily McTernan.
After Brexit: The Eurosceptic dream of an Anglosphere
Authors: Kenny Michael , Pearce Nick
Published: March 2016

The EU referendum will be a battle between competing visions of Britain's place in the world. Michael Kenny and Nick Pearce warn that the concept of an Anglosphere ‐ an unlikely coalition of English‐speaking countries, and a potent element of Eurosceptics’ vision of post‐EU Britain ‐ demands an equally optimistic rebuttal from pro‐Europeans.
Beyond model answers: A new approach to the relationship between economics and politics
Authors: McGovern Alison
Published: March 2016

Economic modelling is vital to our understanding of the world ‐ and even more vital to policymakers. Yet, says Alison McGovern, do they provide us with the certainty that we think they do? And is our focus on economic evidence in political discourse really representative of the bases on which policy decisions are actually made?
Bridging the Gap: A Manual Primer into Design Computing in the Context of Basic Design Education
Authors: Uysal V. Şafak , Topaloğlu Fulden
Published: March 2016

Design education is in need of a wider restructuring to accommodate new developments and paradigmatic shifts brought forth by the information age, all of which capitalise a move towards complexity theory, systems science and digital technologies. The intention of this article is to approach one particular aspect of this need: that is, how basic design education can be reconsidered to establish the arguably broken link between the ‘learning by doing’ tradition of a Bauhaus‐oriented basic design education with the computational and parametric logic necessitated by contemporary design technologies. The authors present the overall outlines of a basic design course as offered in Beykent University Department of Industrial Design in Istanbul, Turkey. The programme consists of a series of exercises grouped in five modules and two ‘binders’ that are structured to link the fundamental notions and operations of design thinking covered in basic design courses of the first year with the analytical and computational‐reasoning competencies that are developed mostly in the later years of design education.
Suppression of IL‐8‐Src signalling axis by 17β‐estradiol inhibits human mesenchymal stem cells‐mediated gastric cancer invasion
Authors: Liu Chung‐Jung , Kuo Fu‐Chen , Wang Chiu‐Lin , Kuo Chao‐Hung , Wang Sophie S.W. , Chen Chiao‐Yun , Huang Yaw‐Bin , Cheng Kuang‐Hung , Yokoyama Kazunari K. , Chen Chun‐Lin , Lu Chien‐Yu , Wu Deng‐Chyang
Published: March 2016

Epidemiologic data show the incidence of gastric cancer in men is twofold higher than in women worldwide. Oestrogen is reported to have the capacity against gastric cancer development. Endogenous oestrogen reduces gastric cancer incidence in women. Cancer patients treated with oestrogens have a lower subsequent risk of gastric cancer. Accumulating studies report that bone marrow mesenchymal stem cells (BMMSCs) might contribute to the progression of gastric cancer through paracrine effect of soluble factors. Here, we further explore the effect of oestrogen on BMMSCs‐mediated human gastric cancer invasive motility. We founded that HBMMSCs notably secrete interleukin‐8 (IL‐8) protein. Administration of IL‐8 specific neutralizing antibody significantly inhibits HBMMSCs‐mediated gastric cancer motility. Treatment of recombinant IL‐8 soluble protein confirmed the role of IL‐8 in mediating HBMMSCs‐up‐regulated cell motility. IL‐8 up‐regulates motility activity through Src signalling pathway in human gastric cancer. We further observed that 17β ‐estradiol inhibit HBMMSCS‐induced cell motility via suppressing activation of IL8‐Src signalling in human gastric cancer cells. 17β‐estradiol inhibits IL8‐up‐regulated Src downstream target proteins including p‐Cas, p‐paxillin, p‐ERK1/2, p‐JNK1/2, MMP9, tPA and uPA. These results suggest that 17β‐estradiol significantly inhibits HBMMSCS‐induced invasive motility through suppressing IL8‐Src signalling axis in human gastric cancer cells.
Human leukocyte antigen typing using buccal swabs as accurate and non‐invasive substitute for venipuncture in children at risk for celiac disease
Authors: Adriaanse Marlou P M , Vreugdenhil Anita C E , Vastmans Véronique , Groeneveld Lisette , Molenbroeck Stefan , Schott Dina A , Voorter Christina E M , Tilanus Marcel G J
Published: March 2016

Background and Aim

Human leukocyte antigen (HLA) typing is an important step in the diagnostic algorithm for celiac disease (CD) and is also used for screening purposes. Collection of blood is invasive and accompanied with emotional impact especially in children. Genetic technological progress now enables HLA typing from buccal cell samples. This study evaluated the reliability and feasibility of HLA typing for CD‐associated HLA polymorphisms using buccal swabs as routine test in high‐risk individuals.

Methods

Blood and buccal swabs of 77 children and adolescents with high risk for CD were prospectively collected in this cohort study. Buccal swab collection was performed either by the investigator at the outpatient clinic or by the patient or its parents at home. To evaluate the possibility of self‐administration, three families performed the test at home. DNA was extracted using an adapted QIAamp method. Quantity, quality, and purity of DNA were recorded. HLA‐DRB1, HLA‐DQA1, and HLA‐DQB1 typing was examined on buccal cell‐derived and blood‐derived DNA at low and, if necessary, high resolution level, using sequence‐specific oligonucleotide and sequence‐based typing, respectively.

Results

DNA isolation using buccal swabs yielded a good quality and sufficient quantity of DNA to perform HLA‐DQ typing in all individuals. HLA typing results on buccal cell‐derived DNA were identical to typing on blood‐derived DNA, also for the self‐administered samples.

Conclusion

Introduction of the buccal swab test for HLA typing of CD risk in routine diagnostics can omit the current venipuncture and enables self‐administration at home. Therefore, the buccal swab test is beneficial for individuals with a clinical suspicion for CD, as well as for screening purposes in high‐risk populations.
A simple, flexible and high‐throughput cloning system for plant genome editing via CRISPR‐Cas system
Authors: Kim Hyeran , Kim Sang‐Tae , Ryu Jahee , Choi Min Kyung , Kweon Jiyeon , Kang Beum‐Chang , Ahn Hyo‐Min , Bae Suji , Kim Jungeun , Kim Jin‐Soo , Kim Sang‐Gyu
Published: March 2016

CRISPR‐Cas9 system is now widely used to edit a target genome in animals and plants. Cas9 protein derived from Streptococcus pyogenes (SpCas9) cleaves double‐stranded DNA targeted by a chimeric single‐guide RNA (sgRNA). For plant genome editing, Agrobacterium‐mediated T‐DNA transformation has been broadly used to express Cas9 proteins and sgRNAs under the control of CaMV 35S and U6/U3 promoter, respectively. We here developed a simple and high‐throughput binary vector system to clone a 19−20 bp of sgRNA, which binds to the reverse complement of a target locus, in a large T‐DNA binary vector containing an SpCas9 expressing cassette. Two‐step cloning procedures: (1) annealing two target‐specific oligonucleotides with overhangs specific to the AarI restriction enzyme site of the binary vector; and (2) ligating the annealed oligonucleotides into the two AarI sites of the vector, facilitate the high‐throughput production of the positive clones. In addition, Cas9‐coding sequence and U6/U3 promoter can be easily exchanged via the GatewayTM system and unique EcoRI/XhoI sites on the vector, respectively. We examined the mutation ratio and patterns when we transformed these constructs into Arabidopsis thaliana and a wild tobacco, Nicotiana attenuata. Our vector system will be useful to generate targeted large‐scale knock‐out lines of model as well as non‐model plant.
REGIONAL VARIATIONS IN LABOR DEMAND ELASTICITY: EVIDENCE FROM U.S. COUNTIES
Authors: Maiti Abhradeep , Indra Debarshi
Published: March 2016

We use a large panel dataset covering the period 1988–2010 to estimate county specific own‐wage elasticity of labor demand in the U.S. for four highly aggregated industries: construction, finance/insurance/real‐estate/service, manufacturing, and retail trade. Our estimation of a random parameter panel data model yields significant evidence of spatial variations in wage elasticity of labor demand. We relate the spatial variation in elasticity to differences in county characteristics like industry specialization, industry competition, levels of natural amenity and urbanization. Using a regression discontinuity approach we also find that probusiness states have higher labor demand elasticity.
Lymphomagenesis‐related gene expression in B cells from sustained virological responders with occult hepatitis C virus infection
Authors: Roque Cuéllar M. C. , García‐Lozano J. R. , Sánchez B. , Praena‐Fernández J. M. , Martínez Sierra C. , Núñez‐Roldán A. , Aguilar‐Reina J.
Published: March 2016

The expression of activation‐induced cytidine deaminase, B‐aggressive lymphoma, cyclin D1 and serine/threonine kinase 15 genes, among others, is increased in B cells from patients with chronic hepatitis C virus (HCV) infection. It is unknown whether the level of expression of these genes in B cells is increased in patients with hepatitis C who have achieved a sustained virological response (SVR) but who have persistent, detectable HCV RNA, so‐called occult infection. Eighty‐three patients who achieved and SVR, 27 with detectable HCV and 56 without detectable HCV RNA, 28 chronic hepatitis C patients and 32 healthy controls were studied. RNA was extracted from B cells, and gene expression levels were measured by RT‐PCR. Patients with chronic HCV and those who achieved an SVR (with and without persistent low‐level HCV RNA) showed a statistically significant higher expression compared to healthy controls, of activation‐induced cytidine deaminase (P = 0.004, P < 0.001 and P = 0.002, respectively), B‐aggressive lymphoma (P < 0.001, P = 0.001 and P = 0.006) and cyclin D1 (P = 0.026, P = 0.001; P = 0.038). For activation‐induced cytidine deaminase patients with an SVR and ‘occult infection’ had a statistically significantly higher expression level than patients with and SVR without ‘occult infection’ (P = 0.014). The higher expression levels found for activation‐induced cytidine deaminase, together with other genes indicates that these B lymphomagenesis‐related genes are upregulated following HCV therapy and this is more marked when HCV can be detected in PBMCs.
Mechanisms ofTritrichomonas foetusPathogenicity in Cats with Insights from Venereal Trichomonosis
Authors: Tolbert M.K. , Gookin J.L.
Published: March 2016

Almost 20 years has passed since trichomonosis was first recognized as a potential cause of diarrhea in domestic cats. Despite progress in confirming disease causation, developing means for diagnosis, and identifying approaches to treatment of the infection, we still know very little about how this parasite causes diarrhea. With increasing recognition of resistance of trichomonosis to treatment with 5‐nitroimidazole drugs, new treatment strategies based on an understanding of disease pathogenesis are needed. In this review, lessons learned from the pathogenesis of venereal trichomonosis in people and cattle are applied to clinical observations of trichomonosis in cats in effort to generate insight into areas where further research may be beneficial.