bluuebunny/crossref_metadata_2025 huggingface dataset:
Due diligence: Plantation Shutters®, South Africa
Authors: Sutherland Margie , Pearson Hayley , Fisher Greg
Published: June 2017

Subject area

Company turnaround, General Management.

Study level/applicability

Executive education, MBA.

Case overview

This is a four-part case study in which the case of a company turnaround emerges as the students work through a series of decision-making processes. In teaching the case, the students would only be given Part A to begin with, about which they need to make decisions as to what they would do, as preparation for the first part of the lecture. After that has been discussed, they are provided with the second part which tells them what in fact happened in the situation and leads them to the next decision point, and so on. The case deals with an entrepreneur hearing about a business that has gone insolvent; it then tracks the process from investigating the small manufacturing and sales company through the various stages of its subsequent remarkable turnaround to the point where the protagonist was voted Entrepreneur of the Year in South Africa. It covers the period 2007 to 2012 and includes the annual financial statements.

Expected learning outcomes

Following are the expected learning outcomes: an understanding of the broad range of management competencies; an understanding of how to turnaround a small organisation; and to experience group-based decision-making.

Supplementary materials

Teaching notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.

Subject code

CSS 11: Strategy.
Using experimentation to understand the 10‐year snowshoe hare cycle in the boreal forest of North America
Authors: Krebs Charles J. , Boonstra Rudy , Boutin Stan
Published: June 2017

Population cycles have long fascinated ecologists from the time of Charles Elton in the 1920s. The discovery of large population fluctuations in undisturbed ecosystems challenged the idea that pristine nature was in a state of balance. The 10‐year cycle of snowshoe hares (Lepus americanusErxleben) across the boreal forests of Canada and Alaska is a classic cycle, recognized by fur traders for more than 300 years.

Since the 1930s, ecologists have investigated the mechanisms that might cause these cycles. Proposed causal mechanisms have varied from sunspots to food supplies, parasites, diseases, predation and social behaviour. Both the birth rate and the death rate change dramatically over the cycle. Social behaviour was eliminated as a possible cause because snowshoe hares are not territorial and do not commit infanticide.

Since the 1960s, large‐scale manipulative experiments have been used to discover the major limiting factors. Food supply and predation quickly became recognized as potential key factors causing the cycle. Experiments adding food and restricting predator access to field populations have been decisive in pinpointing predation as the key mechanism causing these fluctuations.

The immediate cause of death of most snowshoe hares is predation by a variety of predators, including the Canada lynx (Lynx canadensisKerr). The collapse in the reproductive rate is not due to food shortage as was originally thought, but is a result of chronic stress from predator chases.

Five major issues remain unresolved. First, what is the nature of the predator‐induced memory that results in the prolonged low phase of the cycle? Second, why do hare cycles form a travelling wave, starting in the centre of the boreal forest in Saskatchewan and travelling across western Canada and Alaska? Third, why does the amplitude of the cycle vary greatly from one cycle to the next in the same area? Fourth, do the same mechanisms of population limitation apply to snowshoe hares in eastern North American or in similar ecosystems across Siberia? Finally, what effect will climatic warming have on all the above issues? The answers to these questions remain for future generations of biologists to determine.
A co‐drug conjugate of naringenin and lipoic acid mediates neuroprotection in a rat model of oxidative stress
Authors: Saleh Tarek M , Saleh Monique C , Connell Barry J , Song Yang‐Heon
Published: June 2017

Using our in vitro and in vivo models of oxidative stress, the current study was designed to determine the neuroprotective potential of naringenin, alone or in combination with lipoic acid. In our mixed neuronal culture exposed to hypoxia and subsequent reoxygenation, naringenin was shown to provide significant neuroprotection against cell death at a concentration of 2.5 μmol/L. Lipoic acid (LA) did not produce neuroprotection at any concentration tested (0.25‐100 μmol/L). In contrast, when naringenin was covalently combined with LA, producing a novel compound named “VANL‐100”, significant neuroprotection was observed at a concentration as low as 2×10−2 μmol/L (100‐fold more potent). An ELISA for antioxidant capacity demonstrated that naringenin and VANL‐100 likely resulted in neuroprotection by increasing the free radical scavenging capacity of the neuronal cells. Pretreatment of rats with the above compounds prior to middle cerebral artery occlusion (MCAO) followed by reperfusion, showed similar results. Naringenin significantly reduced infarct volume at a dose of 10 mg/kg while VANL‐100 produced significant neuroprotection at a dose as low as 1×10−4 mg/kg (10 000‐fold more potent). This VANL‐100‐induced neuroprotection persisted even when administered 1 and 3 hours into the reperfusion time course. Taken together, these results suggest that our novel compound, VANL‐100 is neuroprotective, likely via a mechanism that involves increasing the antioxidant capacity of neuronal cells. Our results also show that VANL‐100 is 100‐10 000‐fold more potent than the parent compounds, which adds to the growing evidence in support of combination therapy targeting oxidative stress in neurodegenerative diseases.
Targeting protein for Xenopus kinesin‐like protein 2 knockdown enhances radiation sensitivity of human lung squamous carcinoma cell
Authors: Yang Jie , Gao Feng , Xu Xinjian , Wang Yuxiang , Zhu Shuchai
Published: June 2017

The targeting protein for Xenopus kinesin‐like protein 2 (TPX2) has been demonstrated to be associated with the tumourigenesis of many cancers. In the present study, we investigated the role and preliminary mechanism of TPX2 in the resistance of lung squamous carcinoma to radiation therapy. The results showed that SK‐MES‐1R and NCI‐H226R cells were more resistant to X‐ray irradiation than the parental cells (SK‐MES‐1 and NCI‐H226). Moreover, TPX2 was upregulated in the radioresistant cells compared with the parental cells. TPX2 knockdown significantly decreased TPX2 expression in SK‐MES‐1 cells, while TPX2 overexpression increased TPX2 expression in NCI‐H226 cells compared with the corresponding control cells. TPX2 knockdown enhanced the radiosensitivity of SK‐MES‐1 and promoted cell apoptosis following exposure to irradiation, whereas TPX2 overexpression decreased the radiosensitivity of NCI‐H226 and inhibited cell apoptosis. In in vivo studies, the combination of TPX2 knockdown and irradiation significantly inhibited tumour growth, decreased tumour weight, downregulated TPX2 expression in tumour tissue and induced cell apoptosis in nude mice, while TPX2 overexpression exerted an opposite effect. Our results indicated that TPX2 was correlated with cell radioresistance and it might be served as a therapeutic target to enhance cell radiosensitivity in the radiation therapy of lung squamous carcinoma.
High throughput sequencing reveals Drosophila suzukii responses to insecticides
Authors: Mishra Ruchir , Chiu Joanna C. , Hua Gang , Tawari Nilesh R. , Adang Michael J. , Sial Ashfaq A.
Published: June 2017

Global climate change and acquired resistance to insecticides are threats to world food security. Drosophila suzukii, a devastating invasive pest in many parts of the world, causes substantial economic losses to fruit production industries, forcing farmers to apply broad‐spectrum insecticides frequently. This could lead to the development of insecticide resistance. We determined the Lethal Concentration 50 (median lethal concentration, LC50) values of zeta‐cypermethrin, spinosad, and malathion insecticides against D. suzukii colonies established from Clarke and Pierce county Georgia, United States. The LC50 values were 3 fold higher in the Pierce county population for all insecticide treatments. We then used RNA sequencing to analyze the responses of Pierce and Clarke population flies surviving a LC50 treatment of the 3 insecticides. We identified a high number of differentially expressed genes that are likely involved in detoxification and reduced cuticular penetration, especially in the Pierce population, with extensive overlap in differentially expressed genes between the 3 insecticide treatments. Finally, we predicted fewer nonsynonymous single nucleotide variants having deleterious effects on protein function among detoxification, insecticide target, and cuticular protein encoding genes in Pierce flies. Thus a combination of increased gene expression and fewer deleterious single nucleotide variants highlights molecular mechanisms underlying the higher LC50 values for Pierce population flies.
An empirical test of the role of learning in translocation
Authors: Krochmal A. R. , Roth T. C. , O'Malley H.
Published: June 2017

Translocation centers on the introducing, reintroducing, or augmenting populations by moving individuals from existing wild source populations to different locations with purportedly suitable habitat. Despite much research in and application of translocation, this technique is often marred by low success rates. While many possible factors could contribute to low translocation success, outcomes are often improved when researchers engage in a soft release, which provides the animals with the opportunity for extra time to acclimate to their release site, indicating that aspects of learning may play an important role in translocation success. To test the importance of the time available for learning in translocation success, we performed hard and soft releases into an existing population of Eastern painted turtles Chrysemys picta that has experienced seasonal ephemeral water sources and in which resident turtles navigate to new permanent sources of water with extreme precision (±3.5 m) using specific routes known to be facilitated by learning. Translocated adult turtles in both hard‐ and soft‐release groups failed to successfully negotiate upland habitat, even when given 3 months to prospect and learn (the maximum time possible in our system). Likewise, turtles in both groups moved more slowly, stopped more frequently, and were slower to restart movement than resident adults. Finally, both translocated groups exhibited significant drops in body mass and elevated rates of predation. In contrast, juveniles from the same donor population navigated to alternative water successfully, with movements and mortality rates not different from resident animals. These results indicate that complex aspects of cognition beyond time to learn can influence translocation success and highlight the importance of considering how and when animals learn.
Noradrenergic signaling in the VTA modulates cocaine craving
Authors: Solecki Wojciech Barnaba , Szklarczyk Klaudia , Pradel Kamil , Kwiatkowska Krystyna , Dobrzański Grzegorz , Przewłocki Ryszard
Published: June 2017

Exposure to drug‐associated cues evokes drug‐seeking behavior and is regarded as a major cause of relapse. Conditional stimulus upregulates noradrenaline (NA) system activity, but the drug‐seeking behavior depends particularly on phasic dopamine signaling downstream from the ventral tegmental area (VTA). The VTA dopamine‐ergic activity is regulated via the signaling of alpha1‐adrenergic and alpha2‐adrenergic receptors (α1‐ARs and α2‐ARs); thus, the impact of the conditional stimulus on drug‐seeking behavior might involve NAergic signaling in the VTA. To date, the role of VTA ARs in regulating cocaine seeking was not studied. We found that cocaine seeking under extinction conditions in male Sprague–Dawley rats was attenuated by intra‐VTA prazosin or terazosin—two selective α1‐AR antagonists. In contrast, cocaine seeking was facilitated by intra‐VTA administration of the selective α1‐AR agonist phenylephrine as well as α2‐AR antagonist RX 821002, whereas the selective β‐AR antagonist propranolol had no effects. In addition, blockade of α1‐AR in the VTA prevented α2‐AR antagonist‐induced enhancement of cocaine seeking. Importantly, the potential non‐specific effects of the VTA AR blockade on cocaine seeking could be excluded, because none of the AR antagonists influenced sucrose seeking under extinction conditions or locomotor activity in the open field test. These results demonstrate that NAergic signaling potently and selectively regulates cocaine seeking during early cocaine withdrawal via VTA α1‐AR and α2‐AR but not β‐AR. Our findings provide new insight into the NAergic mechanisms that underlie cocaine craving.
Novel role and regulation of HDAC4 in cocaine‐related behaviors
Authors: Penrod Rachel D. , Carreira Maria B. , Taniguchi Makoto , Kumar Jaswinder , Maddox Stephanie A. , Cowan Christopher W.
Published: June 2017

Epigenetic mechanisms have been proposed to contribute to persistent aspects of addiction‐related behaviors. One family of epigenetic molecules that may regulate maladaptive behavioral changes produced by cocaine use are the histone deacetylases (HDACs)—key regulators of chromatin and gene expression. In particular, the class IIa HDACs (HDAC4, HDAC5, HDAC7 and HDAC9) respond to changes in neuronal activity by modulating their distribution between the nucleus and cytoplasm—a process controlled in large part by changes in phosphorylation of conserved residues. Cocaine triggers a transient nuclear accumulation of HDAC5 that functions to limit the development of cocaine reward behavior. However, the role and regulation of the close family member, HDAC4, in cocaine behaviors remain largely unknown. In this study, we report that cocaine and cAMP signaling in striatum produced differential phosphorylation and subcellular localization of HDAC4 and HDAC5. Unlike HDAC5, cocaine exposure induced a modest hyperphosphorylation and nuclear export of HDAC4. Genetic deletion of HDAC4 in the nucleus accumbens reduced acute cocaine‐produced locomotion, maximum locomotor sensitization and cocaine reward‐related behavior. Interestingly, overexpression of an HDAC4 cytoplasm‐concentrated mutant (S266E) increased cocaine reward behavior in the cocaine conditioned place preference assay, suggesting that cocaine‐induced nuclear export of HDAC4 might function to facilitate the development of cocaine reward behaviors through a role in the cell cytoplasm. Together, our findings suggest that, despite high sequence homology, HDAC4 and HDAC5 are oppositely regulated by cocaine‐induced signaling in vivo and have distinct roles in regulating cocaine behaviors.
Locomotor sensitization is expressed by ghrelin and D1 dopamine receptor agonist in the nucleus accumbens core in amphetamine pre‐exposed rat
Authors: Jang Ju Kyong , Kim Wha Young , Cho Bo Ram , Lee Jung Won , Kim Jeong‐Hoon
Published: June 2017

Ghrelin modulates mesolimbic dopaminergic pathways in the brain in addition to its role in feeding. We investigated what roles ghrelin in the nucleus accumbens (NAcc) core may play in mediating locomotor activating effects of amphetamine (AMPH). First, when rats were administered with AMPH (1 mg/kg, i.p.) following a bilateral microinjection of ghrelin (0.1 or 0.5 μg/side) into the NAcc core, their locomotor activity was significantly enhanced, while these effects were blocked by co‐microinjection of ghrelin receptor antagonist (0.5 μg/side) into this site. Second, we pre‐exposed rats to saline or amphetamine (1 mg/kg, i.p.) every 2 to 3 days for a total of four times. After 2 weeks of drug‐free withdrawal period, we examined the effect of saline, ghrelin (0.5 μg/side), D1 dopamine receptor agonist, SKF81297 (0.5 μg/side) or ghrelin (0.5 μg/side) + SKF81297 (0.5 μg/side) directly microinjected into the NAcc core on locomotor activity. When we measured rats' locomotor activity for 1 hour immediately following microinjections, only ghrelin + SKF81297 produces sensitized locomotor activity, while all others have no effects. These results suggest that ghrelin may have a distinct role in the NAcc core to provoke the sensitized locomotor activity induced by psychomotor stimulants, and further, it may produce these effects by interaction with D1 dopamine receptors.
How Does CEO Age Affect Firm Risk?
Authors: Chowdhury Jaideep , Fink Jason
Published: June 2017

Previous research demonstrates that older CEOs are associated with lower firm equity risk and fewer R&D expenditures. We examine the risk‐taking behavior of CEOs and find that not only do older CEOs invest in less R&D, they do so sub‐optimally, in the sense that CEO age distorts the effect of q on R&D investment decisions. We find that it is specifically through the channel of R&D investment that CEO age is associated with the reduction in firm equity risk. Consistent with the sub‐optimality of these distortions, firms with more effective corporate governance do not exhibit these associations.
Who's Leaving Money on the Table? Evidence from IPOs within Business Groups
Authors: Kim Woojin , Lim Chan , Yoon Tae Jun
Published: June 2017

This paper examines how controlling shareholders of business groups may pass on the cost of IPO underpricing to minority shareholders. Based on a sample of IPOs made in Korea, we find that sale of secondary shares in Korea in general does not reduce underpricing as it does in the US. However, we do find less underpricing or even overpricing when the offered shares are directly sold by the controlling shareholders. On the other hand, sale of secondary shares held by affiliated firms leads to a negative market reaction for the selling firms, implying a direct wealth transfer from shareholders of affiliated firms to IPO subscribers. These findings suggest that minority shareholders in certain affiliated firms, or scapegoats, may bear the cost of underpricing while controlling shareholders of the business group remain effectively protected instead.
Sperm DNA damage measured by sperm chromatin structure assay in men with a history of undescended testes
Authors: van Brakel J. , Dinkelman‐Smit M. , de Muinck Keizer‐Schrama S. M. P. F. , Hazebroek F. W. J. , Dohle G. R.
Published: June 2017

The aim of this study was to compare sperm DNA damage between men with a history of congenital undescended testis (UDT) and men with a history of acquired UDT. A long‐term follow‐up study of men with previous UDT was performed. Fifty men with congenital UDT who had undergone orchiopexy at childhood age, 49 men with acquired UDT after a ‘wait‐and‐see’‐protocol (e.g. awaiting spontaneous descent until puberty and perform an orchiopexy in case of non‐decent), and 22 healthy proven fertile men were included. The DNA fragmentation index (DFI) using sperm chromatin structure assay (SCSA) was used to express the level of sperm DNA damage. Decreased fertility potential was considered if DFI was above 30%. Sperm DNA damage was not statistically different between cases of congenital and acquired UDT. DFI was significantly more often >30% in the complete group of men with congenital UDT (9/50; 18%) and in the subgroup with bilateral congenital UDT (3/7; 43%) in comparison with the controls (none) (p‐value 0.049 and 0.01, respectively). Age at orchiopexy in congenital UDT had no statistical effect on DNA damage. In men with acquired UDT, DFI did not statistically differ between those having undergone orchiopexy and those experiencing spontaneous descent. This study supports the hypothesis that UDT is a spectrum representing both congenital UDT and acquired UDT. Sperm DNA damage at adult age is not influenced by age at orchiopexy in congenital UDT cases and by orchiopexy or spontaneous descent in acquired UDT cases.
Prediction of sustained fetal toxicity induced by ketoprofen based on PK/PD analysis using human placental perfusion and rat toxicity data
Authors: Tanaka Shingo , Kanagawa Takeshi , Momma Kazuo , Hori Satoko , Satoh Hiroki , Nagamatsu Takeshi , Fujii Tomoyuki , Kimura Tadashi , Sawada Yasufumi
Published: June 2017

Aim

We encountered a case of fetal toxicity due to ductus arteriosus (DA) constriction in a 36‐week pregnant woman who had applied multiple ketoprofen patches. The aim of the present study was to present the case and develop a model to predict quantitatively the fetal toxicity risk of transdermal administration of ketoprofen.

Methods

Human placenta perfusion studies were conducted to estimate transplacental pharmacokinetic (PK) parameters. Using a developed model and these parameters, human fetal plasma concentration profiles of ketoprofen administered to mothers were simulated. Using pregnant rats, DA constriction and fetal plasma drug concentration after ketoprofen administration were measured, fitted to an Emax model, and extrapolated to humans.

Results

Transplacental transfer value at the steady state of ketoprofen was 4.82%, which was approximately half that of antipyrine (passive marker). The model and PK parameters predicted almost equivalent mother and fetus drug concentrations at steady state after transdermal ketoprofen administration in humans. Maximum DA constriction and maximum plasma concentration of ketoprofen after administration to rat dams were observed at different times: 4 h and 1 h, respectively. The model accurately described the delay in DA constriction with respect to the fetal ketoprofen concentration profile. The model with effect compartment and the obtained parameters predicted that use of multiple ketoprofen patches could potentially cause severe DA constriction in the human fetus, and that fetal toxicity might persist after ketoprofen discontinuation by the mother, as observed in our case.

Conclusion

The present approach successfully described the sustained fetal toxicity after discontinuing the transdermal administration of ketoprofen.
Covariate Selection with Group Lasso and Doubly Robust Estimation of Causal Effects
Authors: Koch Brandon , Vock David M. , Wolfson Julian
Published: June 2017

The efficiency of doubly robust estimators of the average causal effect (ACE) of a treatment can be improved by including in the treatment and outcome models only those covariates which are related to both treatment and outcome (i.e., confounders) or related only to the outcome. However, it is often challenging to identify such covariates among the large number that may be measured in a given study. In this article, we propose GLiDeR (Group Lasso and Doubly Robust Estimation), a novel variable selection technique for identifying confounders and predictors of outcome using an adaptive group lasso approach that simultaneously performs coefficient selection, regularization, and estimation across the treatment and outcome models. The selected variables and corresponding coefficient estimates are used in a standard doubly robust ACE estimator. We provide asymptotic results showing that, for a broad class of data generating mechanisms, GLiDeR yields a consistent estimator of the ACE when either the outcome or treatment model is correctly specified. A comprehensive simulation study shows that GLiDeR is more efficient than doubly robust methods using standard variable selection techniques and has substantial computational advantages over a recently proposed doubly robust Bayesian model averaging method. We illustrate our method by estimating the causal treatment effect of bilateral versus single-lung transplant on forced expiratory volume in one year after transplant using an observational registry.
Clinically distinct trajectories of fatigue and their longitudinal relationship with the disturbance of personal goals following a cancer diagnosis
Authors: Müller Fabiola , Tuinman Marrit A. , Janse Moniek , Almansa Josué , Sprangers Mirjam A. G. , Smink Ans , Ranchor Adelita V. , Fleer Joke , Hagedoorn Mariët
Published: June 2017

Objectives

Most studies on fatigue in patients with cancer aggregate its prevalence and severity on a group level, ignoring the possibility that subgroups of patients may differ widely in their development of fatigue. This study aimed to identify subgroups of patients with clinically distinct trajectories of fatigue from diagnosis to 18 months post‐diagnosis. As fatigue might trigger goal disturbance, the study also identified trajectories of concrete and abstract goal disturbance and longitudinally examined their co‐occurrence with fatigue.

Design

Prospective design with quantitative and qualitative method of data collection.

Methods

Patients with colorectal cancer (n = 183) reported on their levels of fatigue and goal disturbance shortly after diagnosis (T1) and at 7 months (T2) and 18 months (T3) post‐diagnosis. Growth mixture model analyses were performed to identify trajectories of fatigue and goal disturbance. Guidelines for the clinical relevance of fatigue were applied.

Results

Four clinically distinct trajectories of fatigue were identified as follows: (1) persistent severe fatigue (25.4%), (2) moderate fatigue (56.1%), (3) no fatigue (13.8%), and (4) rapidly improving fatigue (4.7%). The majority of patients with cancer reported high disturbance of their concrete goals, while high disturbance of abstract goals was less evident. Fatigue and concrete goal disturbance co‐occurred longitudinally.

Conclusions

The fatigue and goal disturbance experienced from diagnosis to 18 months post‐diagnosis differ considerably for subgroups of patients with cancer. Fatigue and concrete goal disturbance are persistent burdens in the majority of patients. Investigating symptom burden beyond average trends can guide clinicians to identify patients most in need for treatment. Targeting goal disturbance might benefit the psychological well‐being in patients suffering from persistent symptoms.

Statement of contribution

What is already known on this subject?

Fatigue is a common and distressing symptom at all stages of the cancer experience.

Earlier studies suggest that many patients recover from fatigue after treatment completion.

Patients with cancer experience disturbance in their personal goals, which is related to poor psychological well‐being.

What does this study add?

Developments of fatigue and goal disturbance differ between subgroups of patients with cancer but co‐occur within these subgroups.

About 30% of the patients experience severe fatigue after diagnosis, of which only few patients recover within 18 months post‐diagnosis.

Targeting goal disturbance might benefit patients with severe and ongoing symptoms.
Improving precision of ability estimation: Getting more from response times
Authors: Bolsinova Maria , Tijmstra Jesper
Published: June 2017

By considering information about response time (RT) in addition to response accuracy (RA), joint models for RA and RT such as the hierarchical model (van der Linden, 2007) can improve the precision with which ability is estimated over models that only consider RA. The hierarchical model, however, assumes that only the person's speed is informative of ability. This assumption of conditional independence between RT and ability given speed may be violated in practice, and ignores collateral information about ability that may be present in the residual RTs. We propose a posterior predictive check for evaluating the assumption of conditional independence between RT and ability given speed. Furthermore, we propose an extension of the hierarchical model that contains cross‐loadings between ability and RT, which enables one to take additional collateral information about ability into account beyond what is possible in the standard hierarchical model. A Bayesian estimation procedure is proposed for the model. Using simulation studies, the performance of the model is evaluated in terms of parameter recovery, and the possible gain in precision over the standard hierarchical model and an RA‐only model is considered. The model is applied to data from a high‐stakes educational test.
Understanding and improving photo‐control of ion channels in nociceptors with azobenzene photo‐switches
Authors: Mourot Alexandre , Herold Christian , Kienzler Michael A , Kramer Richard H
Published: June 2017

Background and Purpose

The photo‐isomerizable local anaesthetic, quaternary ammonium–azobenzene–quaternary ammonium (QAQ), provides rapid, optical control over pain signalling without involving genetic modification. In darkness or in green light, trans‐QAQ blocks voltage‐gated K+ and Na+ channels and silences action potentials in pain‐sensing neurons. Upon photo‐isomerization to cis with near UV light, QAQ blockade is rapidly relieved, restoring neuronal activity. However, the molecular mechanism of cis and trans QAQ blockade is not known. Moreover, the absorption spectrum of QAQ requires UV light for photo‐control, precluding use deep inside neural tissue.

Experimental Approach

Electrophysiology and molecular modelling were used to characterize the binding of cis and trans QAQ to voltage‐gated K+ channels and to develop quaternary ammonium–ethylamine–azobenzene–quaternary ammonium (QENAQ), a red‐shifted QAQ derivative controlled with visible light.

Key Results

trans QAQ was sixfold more potent than cis QAQ, in blocking current through Shaker K+ channels. Both isomers were use‐dependent, open channel blockers, binding from the cytoplasmic side, but only trans QAQ block was slightly voltage dependent. QENAQ also blocked native K+ and Na+ channels preferentially in the trans state. QENAQ was photo‐isomerized to cis with blue light and spontaneously reverted to trans within seconds in darkness, enabling rapid photo‐control of action potentials in sensory neurons.

Conclusions and Implications

Light‐switchable local anaesthetics provide a means to non‐invasively photo‐control pain signalling with high selectivity and fast kinetics. Understanding the mode of action of QAQ and related compounds will help to design of drugs with improved photo‐pharmacological properties.

Linked Articles

This article is part of a themed section on Recent Advances in Targeting Ion Channels to Treat Chronic Pain. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.12/issuetoc
Optimizing outcomes in pancreas transplantation: Impact of organ preservation time
Authors: Rudolph Ehren N. , Dunn Ty B. , Sutherland David E. R. , Kandaswamy Raja , Finger Erik B.
Published: June 2017

Recent changes to pancreas graft allocation policy have increased the number of organs available for regional and distant sharing, which results in a corresponding increase in preservation time. We sought to systematically assess the impact of cold ischemia time (CIT) on outcomes post‐transplant. A retrospective review of 1253 pancreas transplants performed at a single transplant center was performed to correlate CIT to transplant outcomes. The rate of technical failure (TF) increased with 20+ hours of CIT, with a 2.7‐fold to 6.2‐fold increased rate of TF for pancreas after kidney (PAK), simultaneous pancreas and kidney (SPK), and pancreas transplants overall. Long‐term graft survival was best with <12 hours of CIT; graft failure increased 1.2‐fold to 1.4‐fold with 12‐24 hours of CIT and 2.2‐fold with 24+ hours. CIT had less influence on the pancreas transplant alone category than either SPK or PAK and had markedly more influence on grafts from older (age >25 years) and overweight (body mass index >25) donors. In the final analysis, grafts with <12 hours of CIT performed the best overall, and strategies that reduce CIT (such as early allocation, pre‐recovery cross‐matching, and chartered flights for organs) should be considered whenever possible.
Reducing the risk of post‐endoscopic retrograde cholangiopancreatography pancreatitis
Authors: Elmunzer B. Joseph
Published: June 2017

Pancreatitis is the most common and potentially devastating complication of endoscopic retrograde cholangiopancreatography (ERCP), resulting in significant morbidity, occasional mortality, and increased health‐care expenditure. Accordingly, the prevention of post‐ERCP pancreatitis (PEP) remains a major clinical and research priority. Strategies to reduce the incidence of PEP include thoughtful patient selection, appropriate risk‐stratification, sound procedural technique, prophylactic pancreatic stent placement, and pharmacoprevention. Despite advances in all these areas, however, the incidence of PEP remains as high as 15% in high‐risk cases. Thus, additional research towards the goal of eliminating PEP is necessary. Herein is an evidence‐based review of strategies to prevent pancreatitis after ERCP, focusing on recent important developments in the field.
Socio‐economic status and risk of gestational diabetes mellitus among Chinese women
Authors: Song L. , Shen L. , Li H. , Liu B. , Zheng X. , Zhang L. , Xu S. , Wang Y.
Published: June 2017

Aims

The relationship between socio‐economic status and gestational diabetes mellitus has received little attention. The purpose of this study was to investigate the association between socio‐economic status and risk of gestational diabetes.

Methods

Data were obtained from the ongoing Healthy Baby Cohort study in Hubei Province, China, in 2012–2014. Information on educational level and household income was collected using standard questionnaires during face‐to‐face interviews. Gestational diabetes was defined based on the International Association of Diabetes and Pregnancy Study Group's criteria. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for gestational diabetes in relation to socio‐economic status.

Results

Among 6886 participants, 1005 (14.6%) pregnant women were diagnosed with gestational diabetes. Higher educational level was inversely associated with risk of gestational diabetes (OR, 0.74; 95% CI, 0.58, 0.95 for high school and OR, 0.62; 95% CI, 0.50, 0.76 for college or above). After adjustment for potential confounders, the ORs for gestational diabetes were 0.77 (95% CI, 0.59, 1.00) and 0.65 (95% CI, 0.51, 0.83) for women with high school and college or above education, respectively, compared with women with less than high school education. No significant association between household income and gestational diabetes was observed after adjustment for potential confounders. Subgroup analysis showed that the reduced risk of gestational diabetes with higher educational level was more evident among women with a pre‐pregnancy BMI < 24 kg/m2 (P for interaction = 0.022).

Conclusions

Our findings suggested that educational level was a more robust predictor of gestational diabetes than household income among Chinese women.
Putting promises into practice: The New Aid Architecture in Uganda
Authors: Habraken Rik , Schulpen Lau , Hoebink Paul
Published: June 2017

Via the Paris Declaration and the Accra Agenda for Action the international donor community has delivered a set of promises on ownership, harmonization and co‐ordination. Uganda is an interesting case for assessing progress on Paris Principles and seeing the New Aid Architecture in practice. This article provides a historical overview of the implementation of ‘Paris’ in Uganda from the late 1990s up to 2010, showing that implementation is laggardly and, in more recent years, that earlier progress has been reversed. This is due to donors’ perceptions of Uganda's political structure, and particularly its rampant corruption, and also to different views among donors and their internal adaptability in terms of truly measuring up to the Paris Principles.
Does competition with wind‐pollinated species alter Echium plantagineum's attractiveness to a common pollinator Bombus terrestris?
Authors: FLACHER FLORIANE , HANSART AMANDINE , MOTARD ERIC , FOFANA ABDOU MOUTALAB , VINCENT OCEANE , GESLIN BENOIT , DAJOZ ISABELLE , RAYNAUD XAVIER
Published: June 2017

1. In insect‐pollinated plants, pollinator attraction is influenced by flowers (e.g. number, size) and their associated rewards (e.g. pollen, nectar). These traits can depend on plant interactions. Indeed, below‐ground competition between plants can lead to a decrease in flower or reward production in insect‐pollinated species.

2. Wind‐pollinated plants, in particular, which are almost never studied in plant–pollinator networks, can alter insect‐pollinated plants' attractiveness through competition for nutrients. The response of pollinators to such changes has never been investigated.

3. A pot experiment was carried out in which an insect‐pollinated species, Echium plantagineum, was grown in binary mixture with three wind‐pollinated species selected to exert a panel of competitive interactions. Below‐ground competition was controlled using dividers limiting interspecific root competition. Floral traits of E. plantagineum (i.e. flower production, floral display size, flower size and nectar production) were measured. For each species mixture, the visits (i.e. first visit, number of visits, 10‐min sequences) of Bombus terrestris individuals released in a flight cage containing two pots were followed, one with and one without below‐ground competition.

4. Below‐ground competition significantly affected nectar's sucrose concentration but did not influence flower and nectar production. Likewise, pollinator visits were not influenced by below‐ground competition. Competitor identity significantly influenced flower and reward production of E. plantagineum, with a decrease in the presence of the most competitive wind‐pollinated species. A tendency for faster flower visitation events was also detected in the presence of the least competitive competitor. This study raises new questions regarding the influence of wind‐pollinated plants on plant–pollinator interactions.
The spectrum of aseptic central nervous system infections in southern Germany – demographic, clinical and laboratory findings
Authors: Kaminski M. , Grummel V. , Hoffmann D. , Berthele A. , Hemmer B.
Published: June 2017

Background and purpose

Aseptic infections of the central nervous system (CNS) are frequently observed in Germany. However, no study has systematically addressed the spectrum of aseptic CNS infections in Germany.

Methods

Data on 191 adult patients diagnosed from January 2007 to December 2014 with aseptic meningitis or encephalitis/meningoencephalitis at our hospital were collected by chart review and analyzed for demographic, clinical and laboratory findings. Patients were stratified according to the causative virus and findings were compared between groups.

Results

In our cohort, meningitis was caused in 36% by enterovirus (EV), 15% by herpes simplex virus (HSV), 12% by varicella zoster virus (VZV) and 5% by tick borne encephalitis (TBE). Encephalitis/meningoencephalitis was caused in 13% by HSV, 13% by VZV, and three out of 11 tested patients were positive for TBE. The highest incidence of EV infections was between 25 and 35 years and of HSV infections between 30 and 60 years. VZV infections had a bimodal distribution peaking below 30 and above 70 years. VZV and EV infections were more frequently observed during summer, whereas HSV infections showed no seasonal preference. Inflammatory changes in cerebrospinal fluid (CSF) were highest in HSV and lowest in EV infections.

Conclusions

Polymerase chain reaction tests for HSV, VZV and EV in CSF and TBE serology determined the causative virus in over 60% of tested patients. The age of affected patients, seasonal distribution, disease course and inflammatory changes in CSF differ between groups of patients affected by the most common viral infections.
Discontinuation and non‐publication of neurodegenerative disease trials: a cross‐sectional analysis
Authors: Stefaniak J. D. , Lam T. C. H. , Sim N. E. , Al‐Shahi Salman R. , Breen D. P.
Published: June 2017

Background and purpose

Trial discontinuation and non‐publication represent major sources of research waste in clinical medicine. No previous studies have investigated non‐dissemination bias in clinical trials of neurodegenerative diseases.

Methods

ClinicalTrials.gov was searched for all randomized, interventional, phase II–IV trials that were registered between 1 January 2000 and 31 December 2009 and included adults with Alzheimer's disease, motor neurone disease, multiple sclerosis or Parkinson's disease. Publications from these trials were identified by extensive online searching and contact with authors, and multiple logistic regression analysis was performed to identify characteristics associated with trial discontinuation and non‐publication.

Results

In all, 362 eligible trials were identified, of which 12% (42/362) were discontinued. 28% (91/320) of completed trials remained unpublished after 5 years. Trial discontinuation was independently associated with number of patients (P = 0.015; more likely in trials with ≤100 patients; odds ratio 2.65, 95% confidence interval 1.21–5.78) and phase of trial (P = 0.009; more likely in phase IV than phase III trials; odds ratio 3.90, 95% confidence interval 1.41–10.83). Trial non‐publication was independently associated with blinding status (P = 0.005; more likely in single‐blind than double‐blind trials; odds ratio 5.63, 95% confidence interval 1.70–18.71), number of centres (P = 0.010; more likely in single‐centre than multi‐centre trials; odds ratio 2.49, 95% confidence interval 1.25–4.99), phase of trial (P = 0.041; more likely in phase II than phase IV trials; odds ratio 2.88, 95% confidence interval 1.04–7.93) and sponsor category (P = 0.001; more likely in industry‐sponsored than university‐sponsored trials; odds ratio 5.05, 95% confidence interval 1.87–13.63).

Conclusions

There is evidence of non‐dissemination bias in randomized trials of interventions for neurodegenerative diseases. Associations with trial discontinuation and non‐publication were similar to findings in other diseases. These biases may distort the therapeutic information available to inform clinical practice.
Responses of benthic algal communities and their traits to experimental changes in fine sediments, nutrients and flow
Authors: Neif Érika M. , Graeber Daniel , Rodrigues Liliana , Rosenhøj‐Leth Simon , Jensen Tinna M. , Wiberg‐Larsen Peter , Landkildehus Frank , Riis Tenna , Baattrup‐Pedersen Annette
Published: June 2017

Lowland stream ecosystems are subjected to multiple anthropogenic stressors, usually nutrient enrichment in combination with sedimentation of fine particles and low flow periods in summer. Here, we investigated the temporal development of the benthic algae community in response to these three stressors and linkages to the trait characteristics of the community to explore the mechanisms responsible for stress‐induced community changes.

We investigated the response of benthic algae species composition, traits (life forms, cell size categories), biovolume and chlorophyll a (Chl‐a) concentration to low flow in combination with nutrient enrichment and fine sedimentation in twelve large outdoor stream flumes (12 m long) resembling small streams in size and habitat characteristics. The experiment consisted of two phases: a normal‐flow phase followed by a low‐flow phase (90% current velocity reduction), each spanning 4 weeks. We applied a eutrophication scenario (mean increases of 1.14–5.48 mg N/L and 0.01–0.06 mg P/L in the flumes for dissolved inorganic nitrogen and phosphate respectively) throughout the experiment. Under low flow, we supplemented this with a fine sedimentation scenario (>90% stream bed cover). We took samples once in the normal‐flow phase and every week during the low‐flow phase.

We observed strong responses in the benthic algae community to sudden changes in low flow and fine sedimentation, mediating rapid species turnover with a decreased algal biovolume and increased abundance of large, motile species. However, we did not observe any pronounced responses to nutrient enrichment. In contrast to the observations for other variables, we found a continuous increase in Chl‐a concentration during low flow. This was likely due to continuous fine sedimentation during this phase, reducing light availability which probably resulted in an increase of cell‐level Chl‐a concentration in response to light limitation and lower rates of light‐induced Chl‐a degradation.

The rapid response of the benthic algal community to the applied stressors suggests that even short periods of major stressor exposure may significantly affect benthic algae in lowland systems. We suggest that short‐term stress events may have cascading effects on several important ecosystem processes given the importance of benthic algae for the productivity of these systems.
Female GADD34 mice develop age‐related inflammation and hepatocellular carcinoma
Authors: Nishio Naomi , Hasegawa Tadao , Tatsuno Ichiro , Isaka Masanori , Isobe Ken‐ichi
Published: June 2017

Aim

To analyze the impact of sex on GADD34 function, we studied the aging of female GADD34‐deficient mice and compared them with male GADD34‐deficient mice.

Methods

We used GADD34‐deficient mice on a C57BL/6 background. These mice were fed a normal diet throughout their life. Alternatively, they were fed a high‐fat diet at 3 months‐of‐age. Liver tissues taken from mice were analyzed by hematoxylin–eosin staining and immunohistochemical methods. Fresh liver cells were analyzed by flow cytometry.

Results

We found that female GADD34‐deficient mice did not develop obesity or fatty livers. However, female GADD34‐deficient mice had infiltrations of myeloid cells in the liver, followed by liver atrophy. Many female GADD34‐deficient mice developed hepatocellular carcinoma, whereas female wild‐type (WT) mice did not show hepatocellular carcinoma during aging. Female GADD34‐deficient mice and female WT mice developed the same percentages of lymphoma. Although a high‐fat diet induced a higher level of steatosis in young male GADD34‐deficient mice compared with WT mice, a high‐fat diet induced the same level of steatosis in young female GADD34‐deficient mice compared with WT mice. However, GADD34‐deficient female young mice had a higher level of infiltration of myeloid cells and myofibroblasts than WT mice.

Conclusions

In contrast to male GADD34‐deficient mice, female GADD34‐deficient mice did not show obesity as they aged. However, similar to the males, they developed inflammation followed by hepatocellular carcinoma. Geriatr Gerontol Int 2017; 17: 2593–2601.
Retracted: National home infusion teaching guidelines will improve quality of care and patient outcomes in haemophilia treatment centres across the USA
Authors: Santaella M. E. , Bloomberg M. C. , Anglade D.
Published: June 2017

M. E. Santaella, M. C. Bloomberg, D. Anglade

The above article, published online on 21 June 2017 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editors in Chief, Michael Makris and Craig Kessler, John Wiley & Sons Ltd and the authors. The retraction has been agreed due to the duplicated publication in the journal Research and Practice in Thrombosis and Haemostasis.

References

1. Santaella ME, Bloomberg MC, Anglade D. National home infusion teaching guidelines will improve quality of care and patient outcomes in haemophilia treatment centres across the USA. Haemophilia. 2017. https://doi.org/10.1111/hae.13289

2. Santaella ME, Bloomberg M, Anglade D. Home infusion teaching practices at federally funded hemophilia treatment centers in the United States of America. Res Pract Thromb Haemost. 2017;1:81–89. https://doi.org/10.1002/rth2.12020