bluuebunny/crossref_metadata_2025 huggingface dataset:
Colonies of the fungus Aspergillus niger are highly differentiated to adapt to local carbon source variation
Authors: Daly Paul , Peng Mao , Mitchell Hugh D. , Kim Young‐Mo , Ansong Charles , Brewer Heather , de Gijsel Peter , Lipton Mary S. , Markillie Lye Meng , Nicora Carrie D. , Orr Galya , Wiebenga Ad , Hildén Kristiina S. , Kabel Mirjam A. , Baker Scott E. , Mäkelä Miia R. , de Vries Ronald P.
Published: December 2019

Saprobic fungi, such as Aspergillus niger, grow as colonies consisting of a network of branching and fusing hyphae that are often considered to be relatively uniform entities in which nutrients can freely move through the hyphae. In nature, different parts of a colony are often exposed to different nutrients. We have investigated, using a multi‐omics approach, adaptation of A. niger colonies to spatially separated and compositionally different plant biomass substrates. This demonstrated a high level of intra‐colony differentiation, which closely matched the locally available substrate. The part of the colony exposed to pectin‐rich sugar beet pulp and to xylan‐rich wheat bran showed high pectinolytic and high xylanolytic transcript and protein levels respectively. This study therefore exemplifies the high ability of fungal colonies to differentiate and adapt to local conditions, ensuring efficient use of the available nutrients, rather than maintaining a uniform physiology throughout the colony.
Redox cycling of Fe(II) and Fe(III) in magnetite accelerates aceticlastic methanogenesis by Methanosarcina mazei
Authors: Wang Hui , Byrne James M. , Liu Pengfei , Liu Juan , Dong Xiuzhu , Lu Yahai
Published: December 2019

It has been recently shown that magnetite nanoparticles (nanoFe3O4) can facilitate methanogenic syntrophy but the effect of magnetite on methanogenesis alone remains elusive. Here we show that aceticlastic methanogenesis by Methanosarcina mazei is accelerated by magnetite and is correlated with the redox cycling of structural Fe(II) and Fe(III) in the mineral. An enrichment and its closest pure culture relative, Ms. mazei zm‐15, both obtained from a natural wetland of the Tibetan plateau were tested in this experiment. The Fe(II) to Fe(III) ratios in magnetite, as measured by multiple approaches, show an initial increase in both the methanogenic cultures and the blank preparations containing no microbes. The Fe(II)/Fe(III) ratio then displays a distinct decline followed by an increase towards the end of incubation only in the enrichment and pure culture cultivations. This redox cycling of magnetite is in accordance with the stimulation of aceticlastic methanogenesis. Microscopic observation reveals the precipitation of nanoFe3O4 on methanogen cell surface. The genomic analysis predicts that in addition to electron transfer components essential for aceticlastic methanogenesis, Ms. mazei zm‐15 contains an outer‐surface multiheme c‐type cytochrome (MHC) and a few function‐unknown surface proteins that harbour monoheme motif. We hypothesize that the redox cycling of nanoFe3O4 delivers a positive influence via the MHC to the membrane electron transfer chain and hence promote the aceticlastic methanogenesis.
Joint species distribution modelling with ther‐package Hmsc
Authors: Tikhonov Gleb , Opedal Øystein H. , Abrego Nerea , Lehikoinen Aleksi , de Jonge Melinda M. J. , Oksanen Jari , Ovaskainen Otso
Published: December 2019

Joint Species Distribution Modelling (JSDM) is becoming an increasingly popular statistical method for analysing data in community ecology. Hierarchical Modelling of Species Communities (HMSC) is a general and flexible framework for fitting JSDMs. HMSC allows the integration of community ecology data with data on environmental covariates, species traits, phylogenetic relationships and the spatio‐temporal context of the study, providing predictive insights into community assembly processes from non‐manipulative observational data of species communities.

The full range of functionality of HMSC has remained restricted to Matlab users only. To make HMSC accessible to the wider community of ecologists, we introduce Hmsc3.0, a user‐friendlyrimplementation.

We illustrate the use of the package by applying Hmsc3.0 to a range of case studies on real and simulated data. The real data consist of bird counts in a spatio‐temporally structured dataset, environmental covariates, species traits and phylogenetic relationships. Vignettes on simulated data involve single‐species models, models of small communities, models of large species communities and models for large spatial data. We demonstrate the estimation of species responses to environmental covariates and how these depend on species traits, as well as the estimation of residual species associations. We demonstrate how to construct and fit models with different types of random effects, how to examine MCMC convergence, how to examine the explanatory and predictive powers of the models, how to assess parameter estimates and how to make predictions. We further demonstrate how Hmsc3.0 can be applied to normally distributed data, count data and presence–absence data.

The package, along with the extended vignettes, makes JSDM fitting and post‐processing easily accessible to ecologists familiar withr.
Preparation, structural, microstructural, mechanical, and cytotoxic characterization of Ti‐15Nb alloy for biomedical applications
Authors: Kuroda Pedro Akira Bazaglia , da Silva Luciano Monteiro , Sousa Karolyne dos Santos Jorge , Donato Tatiani Ayako Goto , Grandini Carlos Roberto
Published: December 2019

Titanium alloys are widely used in the biomedical field due to their excellent resistance to corrosion, high mechanical strength/density ratio, low elastic modulus, and good biocompatibility. Niobium is a β‐stabilizer element that has the potential to decrease elastic modulus and possesses excellent corrosion resistance. In this article, Ti‐15Nb alloy was prepared via arc‐melting, with the aim of using it in biomedical applications to replace implants that fail due to mechanical incompatibility with human bone. This Ti‐15Nb alloy was structurally, chemically, and microstructurally characterized. Its mechanical properties were analyzed via Vickers microhardness and elastic modulus measurements. The cytotoxicity of the alloy was evaluated via direct and indirect MTT tests. In the direct MTT test, the cells were grown on alloy and in the indirect test, Ti‐15Nb alloy extracts were prepared (1 g/1 mL at 310 K for 48 hours). The results of chemical composition showed that the alloy produced has good quality and low content of gaseous impurities, such as oxygen and nitrogen. The obtained results for structure and microstructure indicated the presence of the martensite α’ phase. The microhardness of the Ti‐15Nb alloy is superior to that of cp‐Ti due to solid solution hardening, and the alloy has a better elastic modulus as compared to pure titanium. Cytotoxic effects were not observed. The Ti‐15Nb alloy shows good results of mechanical properties and does not show cytotoxic effects. In addition, morphological variations were not found in the cells and good cell adhesion in all the studied conditions was observed. In general, the alloy proposed in this article has satisfactory characteristics as a biomedical material.
Clinical outcomes of venoarterial extracorporeal life support in 462 patients: Single‐center experience
Authors: Zhigalov Konstantin , Sá Michel Pompeu Barros Oliveira , Safonov Dmitrii , Zagitov Ilgiz , Alofesh Ahmad , Pavlova Varvara , Easo Jerry , Eichstaedt Harald C. , Ennker Juergen , Ruhparwar Arjang , Weymann Alexander ,   ITCVR
Published: December 2019

This study aims to investigate the outcomes of venoarterial extracorporeal life support (VA‐ECLS) in a large single‐center patient cohort regarding survival and adverse events. Between June 2009 and March 2019, 462 consecutive patients received VA‐ECLS. The mean age was 66.2 ± 11.9 years. Two patient groups were identified: Group 1—patients with ECLS due to postcardiotomy shock (PCS) after cardiac surgery (PCS, n = 357); Group 2—patients with ECLS due to cardiogenic shock (CS) without previous surgery (nonPCS, n = 105). The primary end point was overall in‐hospital survival, while secondary end points were adverse events during the study period. Overall, the in‐hospital survival rate was 26%. There was no statistically significant difference between the groups: 26.3% for PCS and 24.8% for nonPCS, respectively (P > .05). Weaning from VA‐ECLS was possible in 44.3% for PCS and in 29.5% for nonPCS (P = .004). The strong predictors of overall mortality were postoperative hepatic dysfunction (OR = 14.362, 95%CI = 1.948‐105.858), cardiopulmonary resuscitation > 30 minutes (OR = 6.301, 95%CI = 1.488‐26.673), bleeding with a need for revision (OR = 2.123, 95%CI = 1.343‐3.355), and previous sternotomy (OR = 2.077, 95%CI = 1.021‐4.223). Despite its low survival rates, VA‐ECLS therapy is the last resort and the only lifesaving option for patients in refractory CS. In contrast, there is still a lack of evidence for VA‐ECLS in PCS patients. Future studies are warranted to evaluate the outcomes of VA‐ECLS therapy after cardiac surgery.
Effects of left ventricular assist device on heart failure patients: A bioinformatics analysis
Authors: Li Guanhua , Chen Zhibo , Zhang Yu , Wu Zhichao , Zheng Junmeng
Published: December 2019

With the acceleration of demographic aging, heart failure has become a global public health issue. Left ventricular assist device (LVAD) provides a therapeutic option serving as a bridge to transplantation or destination treatment for end‐stage heart failure. However, neither the molecular mechanism nor the gene expression profile of LVAD pathophysiology is well understood. Microarray dataset (GSE21610) was retrieved from the online database of the gene expression omnibus (GEO). Differentially expressed genes (DEGs) between microarrays obtained before and after LVAD therapy were analyzed using GEO2R. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis were carried out, followed by protein–protein interaction (PPI) network construction, which was further visualized by the Cytoscape software. Finally, a target gene‐microRNA (miRNA) network was built using the NetworkAnalyst to predict potential miRNA interactions. A total of 36 upregulated DEGs and 14 downregulated DEGs were screened out. Five hub genes with the highest degree of connectivity were identified, including CCL2, CX3CR1, CD163, TLR7, and SERPINE1. CCL2 was identified as the most outstanding hub gene which is specially regulated by miR‐124, miR‐141, and miR‐495. Our study indicates that CCL2 is crucial to the LVAD pathophysiology. The identified hub genes may be involved in cardiac inflammatory responses, remodeling, and the chemokine signaling pathway. These DEGs, pathways, hub genes, miRNAs are valuable for further investigations. This study provides a better understanding of the gene expression profile in LVAD pathophysiology.
Procalcitonin‐guided protocol decreased the antibiotic use in paediatric patients with severe bronchiolitis
Authors: Alejandre Carme , Balaguer Mònica , Guitart Carmina , Torrús Isabel , Felipe Aida , Launes Cristian , Cambra Francisco José , Jordan Iolanda
Published: December 2019

Aim

Our aim was to determine the effectiveness and safety of a procalcitonin‐guided protocol to decrease antibiotic use in infants with severe bronchiolitis.

Methods

This prospective, observational study was conducted at the Hospital Sant Joan de Déu from 2010 to 2017. Patients under the age of one were included if they were diagnosed with bronchiolitis, had a suspected bacterial infection and were admitted to the paediatric intensive care unit. A procalcitonin‐guided protocol was established in 2014, and two cohorts were compared before and after implementation: 340 in 2010‐2014 and 366 in 2015‐2017.

Results

We recruited 706 patients (58.6% male) with a median age of 47 days and an interquartile range of 25.0‐100.2. The rate for antibiotic use was 79.9%, and this differed before and after implementation (88.2% vs 72.1%, P = .003). Antibiotic stewardship and withdrawal decisions were higher after implementation (22.3% vs 36.4%, P = .005). The length of antibiotic treatment was also different between the two periods (8.65 ± 4.8 days vs 5.05 ± 3.18 days, P = .023). No adverse outcomes were observed due to the implementation of the protocol.

Conclusion

The implementation of a procalcitonin‐guided protocol seems to lead to a safe and general decrease in antibiotic use in paediatric patients with severe bronchiolitis.
Probing renal blood volume with magnetic resonance imaging
Authors: Niendorf Thoralf , Seeliger Erdmann , Cantow Kathleen , Flemming Bert , Waiczies Sonia , Pohlmann Andreas
Published: December 2019

Damage to the kidney substantially reduces life expectancy. Renal tissue hypoperfusion and hypoxia are key elements in the pathophysiology of acute kidney injury and its progression to chronic kidney disease. In vivo assessment of renal haemodynamics and tissue oxygenation remains a challenge. Blood oxygenation level–dependent (BOLD) magnetic resonance imaging (MRI) is sensitive to changes in the effective transversal relaxation time (T2*) in vivo, and is non‐invasive and indicative of renal tissue oxygenation. However, the renal T2* to tissue pO2relationship is not governed exclusively by renal blood oxygenation, but is affected by physiological confounders with alterations in renal blood volume fraction (BVf) being of particular relevance. To decipher this interference probing renal BVf is essential for the pursuit of renal MR oximetry. Superparamagnetic iron oxide nanoparticle (USPIO) preparations can be used as MRI visible blood pool markers for detailing alterations in BVf. This review promotes the opportunities of MRI‐based assessment of renal BVf. Following an outline on the specifics of renal oxygenation and perfusion, changes in renal BVf upon interventions and their potential impact on renal T2* are discussed. We also describe the basic principles of renal BVf assessment using ferumoxytol‐enhanced MRI in the equilibrium concentration regimen. We demonstrate that ferumoxytol does not alter control of renal haemodynamics and oxygenation. Preclinical applications of ferumoxytol enhanced renal MRI as well as considerations for its clinical implementation for examining renal BVf changes are provided alongside practical considerations. Finally, we explore the future directions of MRI‐based assessment of renal BVf.
Efficacy and safety of induction therapy with calcineurin inhibitors followed by vedolizumab maintenance in 71 patients with severe steroid‐refractory ulcerative colitis
Authors: Ollech Jacob E. , Dwadasi Sujaata , Rai Victoria , Peleg Noam , Normatov Inessa , Israel Amanda , Sossenheimer Philip H. , Christensen Britt , Pekow Joel , Dalal Sushila R. , Sakuraba Atsushi , Cohen Russell D. , Rubin David T.
Published: December 2019

Background

Following induction therapy with a calcineurin inhibitor (CNI) in severe ulcerative colitis, transitioning to vedolizumab as maintenance therapy could be an option.

Aim

To report on the largest cohort of patients successfully induced with CNIs who were transitioned to vedolizumab maintenance therapy.

Methods

This is a retrospective observational study of adult patients with severe steroid‐refractory ulcerative colitis. Patients were included if they were induced with a CNI followed by maintenance therapy with vedolizumab between January 2014 and December 2018. The primary endpoint was colectomy‐free survival. Secondary endpoints included survival without vedolizumab discontinuation as well as clinical, steroid‐free and biochemical remission at week 14.

Results

A total of 71 patients (59% male) were treated with vedolizumab after induction therapy with CNIs for severe steroid‐refractory colitis. Patients were followed for a median time of 25 months (IQR 16‐36). Colectomy‐free survival rates from vedolizumab initiation were 93% at 3 months, 67% at 1 year and 55% at 2 years. At the end of induction with vedolizumab at week 14, 50% of patients were in clinical remission, and 62% of patients had a normal CRP. At 1 and 2 years following vedolizumab initiation, 43% and 28% of patients were still on vedolizumab respectively. Vedolizumab was dose escalated to infusions every 4 weeks in 44% of patients. The median time to dose escalation was 5.6 months (IQR 4.1‐8.2). No serious adverse events were recorded in our patient cohort.

Conclusions

Transitioning to vedolizumab following induction of remission with CNIs is effective and safe.
The role of academic buoyancy and emotions in students’ learning‐related expectations and behaviours in primary school
Authors: Hirvonen Riikka , Putwain David W. , Määttä Sami , Ahonen Timo , Kiuru Noona
Published: December 2019

Background

Academic buoyancy refers to students’ ability to come through ordinary challenges they face in the academic context, and it can positively contribute to students’ beliefs and behaviours in learning situations. Although buoyancy has been found to be related to positive academic outcomes, previous studies have not examined how buoyancy influences academic emotions in learning situations and how these emotions further affect students’ learning‐related expectations and behaviours.

Aims

This study investigated to what extent academic buoyancy predicts students’ failure expectations, avoidance behaviour, and task‐oriented planning in learning situations, and to what extent academic emotions mediate the effect of academic buoyancy on these expectations and behaviours.

Sample

A total of 845 Finnish students in the sixth grade of primary school.

Methods

Self‐report data for academic buoyancy and academic emotions in the autumn semester and learning‐related expectations and behaviours in the spring semester were analysed using structural equation modelling, controlling for gender, grade point average, and previous levels of learning‐related expectations and behaviours.

Results

The findings showed that high academic buoyancy indirectly predicted lower avoidance behaviour, fewer failure expectations, and higher task‐oriented planning via academic emotions. High academic buoyancy was related to high enjoyment and hope as well as low boredom and hopelessness, which further predicted low failure expectations. High hope and low boredom also predicted low avoidance behaviour, and high hope was associated with high task‐oriented planning.

Conclusions

The findings suggest that academic buoyancy supports positive expectations and adaptive behaviours in learning situations through the regulation of emotions.
Historical Everyday Geopolitics on the Chile‐Peru Border
Authors: Freeman Cordelia
Published: December 2019

Geopolitics is increasingly seen by scholars as occurring in everyday spaces and performed by ordinary people. This paper extends this idea to historical work to examine how citizens themselves (re)produce geopolitics at the time of historical events. It does so through a case study of geopolitical tension on the Chile‐Peru border in the 1970s. Through oral histories and newspaper analysis, a historical everyday geopolitics approach reveals how those living in the Chilean border city of Arica played a part in promoting national and border security. This centres the embodied and emotional experiences of those affected by violence and conflict.
Interventions in the B‐type natriuretic peptide signalling pathway as a means of controlling chronic itch
Authors: Meng Jianghui , Chen Weiwei , Wang Jiafu
Published: December 2019

Chronic itch poses major health care and economic burdens worldwide. In 2013, B‐type natriuretic peptide (BNP) was identified as an itch‐selective neuropeptide and shown to be both necessary and sufficient to produce itch behaviour in mice. Since then, mechanistic studies of itch have increased, not only at central levels of the spinal relay of itch signalling but also in the periphery and skin. In this review, we have critically analysed recent findings from complementary pharmacological and physiological approaches, combined with genetic strategies to examine the role of BNP in itch transduction and modulation of other pruritic proteins. Additionally, potential targets and possible strategies against BNP signalling are discussed for developing novel therapeutics in itch. Overall, we aim to provide insights into drug development by altering BNP signalling to modulate disease symptoms in chronic itch, including conditions for which no approved treatment exists.
Fluorescent ligands: Bringing light to emerging GPCR paradigms
Authors: Soave Mark , Briddon Stephen J. , Hill Stephen J. , Stoddart Leigh A.
Published: December 2019

In recent years, several novel aspects of GPCR pharmacology have been described, which are thought to play a role in determining the in vivo efficacy of a compound. Fluorescent ligands have been used to study many of these, which have also required the development of new experimental approaches. Fluorescent ligands offer the potential to use the same fluorescent probe to perform a broad range of experiments, from single‐molecule microscopy to in vivo BRET. This review provides an overview of the in vitro use of fluorescent ligands in further understanding emerging pharmacological paradigms within the GPCR field, including ligand‐binding kinetics, allosterism and intracellular signalling, along with the use of fluorescent ligands to study physiologically relevant therapeutic agents.
Fulditoxin, representing a new class of dimeric snake toxins, defines novel pharmacology at nicotinic ACh receptors
Authors: Foo Chun Shin , Jobichen Chacko , Hassan‐Puttaswamy Varuna , Dekan Zoltan , Tae Han‐Shen , Bertrand Daniel , Adams David J. , Alewood Paul F. , Sivaraman J. , Nirthanan Selvanayagam , Kini R. Manjunatha
Published: December 2019

Background and Purpose

Animal toxins have contributed significantly to our understanding of the neurobiology of receptors and ion channels. We studied the venom of the coral snake Micrurus fulvius fulvius and identified and characterized the structure and pharmacology of a new homodimeric neurotoxin, fulditoxin, that exhibited novel pharmacology at nicotinic ACh receptors (nAChRs).

Experimental Approach

Fulditoxin was isolated by chromatography, chemically synthesized, its structure determined by X‐ray crystallography, and its pharmacological actions on nAChRs characterized by organ bath assays and two‐electrode voltage clamp electrophysiology.

Key Results

Fulditoxin's distinct 1.95‐Å quaternary structure revealed two short‐chain three‐finger α‐neurotoxins (α‐3FNTxs) non‐covalently bound by hydrophobic interactions and an ability to bind metal and form tetrameric complexes, not reported previously for three‐finger proteins. Although fulditoxin lacked all conserved amino acids canonically important for inhibiting nAChRs, it produced postsynaptic neuromuscular blockade of chick muscle at nanomolar concentrations, comparable to the prototypical α‐bungarotoxin. This neuromuscular blockade was completely reversible, which is unusual for snake α‐3FNTxs. Fulditoxin, therefore, interacts with nAChRs by utilizing a different pharmacophore. Unlike short‐chain α‐3FNTxs that bind only to muscle nAChRs, fulditoxin utilizes dimerization to expand its pharmacological targets to include human neuronal α4β2, α7, and α3β2 nAChRs which it blocked with IC50 values of 1.8, 7, and 12 μM respectively.

Conclusions and Implications

Based on its distinct quaternary structure and unusual pharmacology, we named this new class of dimeric Micrurus neurotoxins represented by fulditoxin as Σ‐neurotoxins, which offers greater insight into understanding the interactions between nAChRs and peptide antagonists.
Haemodynamic effects of the flavonoid quercetin in rats revisited
Authors: Vrolijk Misha F. , van Essen Helma , Opperhuizen Antoon , Bast Aalt , Janssen Ben J.
Published: December 2019

Background and Purpose

The flavonoid quercetin increased the in vitro potency of the α1‐antagonist tamsulosin to reduce phenylephrine‐dependent arterial contractions by 10‐fold. To examine if this supplement–drug interaction luxates hypotensive and orthostatic events in vivo, several set of studies were conducted in spontaneously hypertensive (SHR) and normotensive (Wistar Kyoto [WKY]) rats.

Experimental Approach

First, in rats pretreated with quercetin or its vehicle, responses to phenylephrine and tamsulosin were examined. Second, tamsulosin‐induced changes in renal, mesenteric, hindquarter and carotid conductance were compared in quercetin‐ and vehicle‐treated rats instrumented with Doppler flow probes. Animals were also placed on a tilt table to record regional haemodynamic changes to orthostatic challenges. Third, adult SHR were instrumented with telemeters to measure 24‐hr patterns of BP. Recordings were made before and during a 5‐week oral treatment of quercetin. Finally, pre‐hypertensive SHR were treated with quercetin from 4 to 8 weeks of age and arterial pressure was measured at 8 and 12 weeks.

Key Results

Pretreatment with quercetin did not influence the responses to phenylephrine and tamsulosin, in neither WKY nor SHR. While tamsulosin treatment and tilting lowered BP and increased conductance in all vascular beds, effect size was not influenced by pretreatment with quercetin. Prolonged treatment with quercetin, in either prehypertensive SHR or adult SHR with established hypertension did not lower BP.

Conclusions and Implications

Cumulatively, these data demonstrate that quercetin does not amplify haemodynamic effects of tamsulosin or tilting in vivo in rats and has no effect on BP development in SHR.
Identification, preclinical profile, and clinical proof of concept of an orally bioavailable pro‐drug of miridesap
Authors: Richards Duncan , Bamford Mark , Liefaard Lia , Haque Nazneen , Lewis Gareth , Storey Jim , Fernando Disala , Kumar Subramanya , Thompson Douglas , Holmes Duncan S.
Published: December 2019

Background and Purpose

Miridesap, a depleter of serum amyloid P component (SAP), forms an essential component of a novel approach to remove systemic amyloid deposits; low oral bioavailability necessitates that it is given parenterally. We sought to identify and clinically characterise a pro‐drug that preserves the pharmacological properties of miridesap while having adequate oral bioavailability and physical stability.

Experimental Approach

We utilised a preclinical screening cascade focused on appropriate physicochemical properties, physical and gut stability, and conversion to miridesap in liver microsomes and blood. GSK3039294 (GSK294) had the desired in vitro profile and progressed to preclinical in vivo pharmacokinetic and safety assessments. Based on a favourable profile, it was tested in healthy participants after single and repeat dosing.

Key Results

GSK294 was highly soluble and stable in simulated gastric and intestinal fluids, stable in intestinal microsomes, and permeable in Madine Darby Canine Kidney type II cells. GSK294 was rapidly hydrolysed to miridesap and its mono pro‐drug ester in blood and liver microsomes. GSK294 showed good oral bioavailability of miridesap in rats and dogs. Following administration of GSK294 600 mg QD for 7 days in humans, pharmacodynamically active concentrations of miridesap were achieved with substantial and sustained depletion of plasma SAP. The study was terminated due to observations of arrhythmia, the relation of which to GSK294 remains unclear.

Conclusion and Implications

Using a preclinical screening cascade, we identified a pro‐drug for a palindromic molecule with unique pharmacology (miridesap). The pro‐drug depleted circulating SAP with a time course and extent similar to that of parenterally administered miridesap.
Ant‐termite interactions: an important but under‐explored ecological linkage
Authors: Tuma Jiri , Eggleton Paul , Fayle Tom M.
Published: December 2019

Animal interactions play an important role in understanding ecological processes. The nature and intensity of these interactions can shape the impacts of organisms on their environment. Because ants and termites, with their high biomass and range of ecological functions, have considerable effects on their environment, the interaction between them is important for ecosystem processes. Although the manner in which ants and termites interact is becoming increasingly well studied, there has been no synthesis to date of the available literature. Here we review and synthesise all existing literature on ant–termite interactions. We infer that ant predation on termites is the most important, most widespread, and most studied type of interaction. Predatory ant species can regulate termite populations and subsequently slow down the decomposition of wood, litter and soil organic matter. As a consequence they also affect plant growth and distribution, nutrient cycling and nutrient availability. Although some ant species are specialised termite predators, there is probably a high level of opportunistic predation by generalist ant species, and hence their impact on ecosystem processes that termites are known to provide varies at the species level. The most fruitful future research direction will be to evaluate the impact of ant–termite predation on broader ecosystem processes. To do this it will be necessary to quantify the efficacy both of particular ant species and of ant communities as a whole in regulating termite populations in different biomes. We envisage that this work will require a combination of methods, including DNA barcoding of ant gut contents along with field observations and exclusion experiments. Such a combined approach is necessary for assessing how this interaction influences entire ecosystems.
Longitudinal trajectories of severe wheeze exacerbations from infancy to school age and their association with early‐life risk factors and late asthma outcomes
Authors: Deliu Matea , Fontanella Sara , Haider Sadia , Sperrin Matthew , Geifman Nophar , Murray Clare , Simpson Angela , Custovic Adnan
Published: December 2019

Introduction

Exacerbation‐prone asthma subtype has been reported in studies using data‐driven methodologies. However, patterns of severe exacerbations have not been studied.

Objective

To investigate longitudinal trajectories of severe wheeze exacerbations from infancy to school age.

Methods

We applied longitudinal k‐means clustering to derive exacerbation trajectories among 887 participants from a population‐based birth cohort with severe wheeze exacerbations confirmed in healthcare records. We examined early‐life risk factors of the derived trajectories, and their asthma‐related outcomes and lung function in adolescence.

Results

498/887 children (56%) had physician‐confirmed wheeze by age 8 years, of whom 160 had at least one severe exacerbation. A two‐cluster model provided the optimal solution for severe exacerbation trajectories among these 160 children: “Infrequent exacerbations (IE)” (n = 150, 93.7%) and “Early‐onset frequent exacerbations (FE)” (n = 10, 6.3%). Shorter duration of breastfeeding was the strongest early‐life risk factor for FE (weeks, median [IQR]: FE, 0 [0‐1.75] vs. IE, 6 [0‐20], P < .001). Specific airway resistance (sRaw) was significantly higher in FE compared with IE trajectory throughout childhood. We then compared children in the two exacerbation trajectories with those who have never wheezed (NW, n = 389) or have wheezed but had no severe exacerbations (WNE, n = 338). At age 8 years, FEV1/FVC was significantly lower and FeNO significantly higher among FE children compared with all other groups. By adolescence (age 16), subjects in FE trajectory were significantly more likely to have current asthma (67% FE vs. 30% IE vs. 13% WNE, P < .001) and use inhaled corticosteroids (77% FE vs. 15% IE vs. 18% WNE, P < .001). Lung function was significantly diminished in the FE trajectory (FEV1/FVC, mean [95%CI]: 89.9% [89.3‐90.5] vs. 88.1% [87.3‐88.8] vs. 85.1% [83.4‐86.7] vs. 74.7% [61.5‐87.8], NW, WNE, IE, FE respectively, P < .001).

Conclusion

We have identified two distinct trajectories of severe exacerbations during childhood with different early‐life risk factors and asthma‐related outcomes in adolescence.
In vitro retention force changes during cyclic dislodging of three novel attachment systems for implant overdentures with different implant angulations
Authors: Maniewicz Sabrina , Badoud Isabelle , Herrmann François R. , Chebib Najla , Ammann Patrick , Schimmel Martin , Müller Frauke , Srinivasan Murali
Published: December 2019

Objectives

This in vitro study aimed to compare changes in retentive force due to cyclic dislodging of three novel un‐splinted attachments.

Materials and Methods

Experimental models simulating a mandibular two‐implant overdenture situation, with implants positioned with various interimplant discrepancies (0°, 20°, 40°, and 60°) were fabricated. Three attachment systems were tested, “N”: a straight or 15°‐angulated stud; “L”: a sole straight stud; and “C”: a straight or individually angulated stud. All models underwent wet testing and were subjected to 10,000 insertion–removal cycles in a universal testing machine. The mean retentive forces were calculated for cycles 10, 100, 1,000, 5,000, and 10,000. Multiple mixed‐effects linear regression models were applied for statistical analyses (⍺ < 0.05).

Results

“N” demonstrated an increasing retention until 1,000 cycles, which subsequently diminished back to its initial retention at 10,000 cycles, showing no significant loss during the entire experiment. Statistical models demonstrated no effect of implant angulation on retention, except for 60° after 10,000 cycles (p < .05). “L” showed an early peak at 100 cycles and did not significantly lose retentive force before 5,000 cycles. Angulations of 40° or higher were shown to lead to lower retentive forces (0° vs. 40° cycle 5,000: p < .05; 0° vs. 60° cycle 100: p < .05, ≥cycle 1,000: p < .001). “C” showed stable retentive forces with no significant loss only at 10,000 cycles (all angles: p < .001) or 5,000 cycles (0° vs. 60°: p < .05).

Conclusions

All systems showed retentive forces promising successful clinical use in implant overdentures, even in situations with extremely angulated implants. Specific abutments compensating interimplant angulation maintain retention longer in situations with high axe divergencies.
A framework for evaluating the impact of the IUCN Red List of threatened species
Authors: Betts Jessica , Young Richard P. , Hilton‐Taylor Craig , Hoffmann Michael , Rodríguez Jon Paul , Stuart Simon N. , Milner‐Gulland E.J.
Published: December 2019

The International Union for Conservation of Nature (IUCN) Red List of Threatened Species, a species extinction risk assessment tool, has been guiding conservation efforts for over 5 decades. It is widely assumed to have been instrumental in preventing species from moving closer to extinction and driving recoveries. However, the impact of the IUCN Red List in guiding conservation has not been evaluated. We conducted, transcribed, and coded interviews with experts who use the IUCN Red List across a range of sectors to understand how the list is used in conservation. We developed a theory of change to illustrate how and why change is expected to occur along causal pathways contributing to the long‐term goal of the IUCN Red List and an evaluation framework with indicators for measuring the impact of the IUCN Red List in generating scientific knowledge, raising awareness among stakeholders, designating priority conservation sites, allocating funding and resources, influencing development of legislation and policy, and guiding targeted conservation action (key themes). Red‐list assessments were the primary input leading to outputs (scientific knowledge, raised awareness), outcomes (better informed priority setting, access to funding and resource availability, improved legislation and policy), and impact (implemented conservation action leading to positive change) that have resulted in achievement of IUCN Red List goals. To explore feasibility of attributing the difference made by the IUCN Red List across themes, we studied increased scientific knowledge, raised awareness, access to funding and resource allocation, and increased conservation activity. The feasibility exploration showed increased scientific knowledge over time identified through positive trends in publications referring to the IUCN Red List in the literature; raised awareness of the list following high IUCN activity identified by peaks in online search activity; an increased proportion of conservation funding bodies requesting IUCN Red List status in the application process; and, based on interviews with Amphibian Specialist Group members, red‐list assessments were essential in connecting relevant stakeholders and ensuring conservation action. Although we identified the IUCN Red List as a vital tool in global conservation efforts, it was challenging to measure specific impacts because of its ubiquitous nature. We are the first to identify the influence of the IUCN Red List on conservation.
Non‐negligible rate of needle tract seeding after endoscopic ultrasound‐guided fine‐needle aspiration for patients undergoing distal pancreatectomy for pancreatic cancer
Authors: Yane Kei , Kuwatani Masaki , Yoshida Makoto , Goto Takuma , Matsumoto Ryusuke , Ihara Hideyuki , Okuda Toshinori , Taya Yoko , Ehira Nobuyuki , Kudo Taiki , Adachi Takeya , Eto Kazunori , Onodera Manabu , Sano Itsuki , Nojima Masanori , Katanuma Akio
Published: December 2019

Background and aims

Needle tract seeding after preoperative endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) for pancreatic body and tail cancer has been reported. This study aimed to investigate the long‐term outcomes, including the needle tract seeding ratio, of patients undergoing distal pancreatectomy for pancreatic body and tail cancer diagnosed preoperatively by EUS‐FNA.

Methods

This retrospective, observational cohort study assessed patients from three university hospitals and 11 tertiary referral centers. All patients who underwent distal pancreatectomy for invasive cancer of the pancreatic body and tail between January 2006 and December 2015 were identified and reviewed. Needle tract seeding rate, recurrence‐free survival (RFS), and overall survival (OS) were evaluated.

Results

Of the 301 total patients analyzed, 176 underwent preoperative EUS‐FNA (EUS‐FNA group) and 125 did not (non‐EUS‐FNA group). The median follow‐up periods of the EUS‐FNA group and non‐EUS‐FNA group were 32.8 and 30.1 months. Six patients (3.4%) in the EUS‐FNA group were diagnosed as having needle tract seeding. The 5‐year cumulative needle tract seeding rate estimated using Fine and Gray's method was 3.8% (95% CI 1.6–7.8%). The median RFS or OS was not significantly different between the EUS‐FNA group and the non‐EUS‐FNA group (23.7 vs 16.9 months: P = 0.205; 48.0 vs 43.9 months: P = 0.392).

Conclusion

Although preoperative EUS‐FNA for pancreatic body and tail cancer has no negative effect on RFS or OS, needle tract seeding after EUS‐FNA was observed to have a non‐negligible rate. (UMIN000030719)
How point‐of‐care HbA1c testing changes the behaviour of people with diabetes and clinicians – a qualitative study
Authors: Hirst J. A. , Farmer A. J. , Williams V.
Published: December 2019

Aim

To explore adults with diabetes and clinician views of point‐of‐care HbA1c testing.

Methods

Adults with diabetes and HbA1c ≥ 58 mmol/mol (7.5%) receiving HbA1c point‐of‐care testing in primary care were invited to individual interviews. Participants were interviewed twice, once prior to point‐of‐care testing and once after 6 months follow‐up. Clinicians were interviewed once. A thematic framework based on an a priori framework was used to analyse the data.

Results

Fifteen participants (eight women, age range 30–70 years, two Asians, 13 white Europeans) were interviewed. They liked point‐of‐care testing and found the single appointment more convenient than usual care. Receiving the test result at the appointment helped some people understand how some lifestyle behaviours affected their control of diabetes and motivated them to change behaviours. Receiving an immediate test result reduced the anxiety some people experience when waiting for a result. People thought there was little value in using point‐of‐care testing for their annual review. Clinicians liked the point‐of‐care testing but expressed concerns about costs.

Conclusions

This work suggests that several features of point‐of‐care testing may encourage behavioural change. It helped some people to link their HbA1c result to recent lifestyle behaviours, thereby motivating behavioural change and reinforcing healthy lifestyle choices.
Combined individual and family therapy in comparison to treatment as usual for people at‐risk of psychosis: A feasibility study (IF CBT): Trial rationale, methodology and baseline characteristics
Authors: Law Heather , Izon Emma , Au‐Yeung Karmen , Morrison Anthony P. , Byrne Rory , Notley Caitlin , Yung Alison , Norrie John , French Paul
Published: December 2019

Aims

Current National Institute for Health and Care Excellence (NICE) guidelines for psychosis recommend psychological therapy with or without family intervention for individuals at‐risk of developing psychosis. NICE guidelines have a specific research recommendation to investigate the clinical and cost effectiveness of combined individual and family intervention. We report the rationale, design and baseline characteristics of a feasibility study which aimed to investigate combined Individual and Family Cognitive Behavioural Therapy (IFCBT) for those at‐risk of developing psychosis.

Methods

The IFCBT study was a single blind, pilot randomized controlled trial (RCT) to compare a combined individual and family Cognitive Behavioural Therapy (CBT) intervention to treatment as usual. Participants were assessed using the Comprehensive Assessment of the At‐risk Mental State (CAARMS) and randomly allocated to either therapy or enhanced treatment as usual (ETAU). All participants were followed up at 6 and 12 months. Primary feasibility outcomes were recruitment and retention of participants. Secondary outcomes included transition to psychosis and assessment of mood, anxiety and the relationship of the individual and nominated family member.

Results

We report data showing entry into the study from initial enquiry to randomization. We report the characteristics of the recruited sample of individuals (n = 70) and family members (n = 70) at baseline.

Conclusions

The study recruited to 92% of target demonstrating it is feasible to identify and recruit participants. Our study aimed to add to the current evidence base regarding the utility of family interventions for people at‐risk of psychosis.
Impact of exposure to severe suicidal behaviours in patients during psychiatric training: An online French survey
Authors: Leaune Edouard , Durif‐Bruckert Christine , Noelle Hugo , Joubert Fabien , Ravella Noémie , Haesebaert Julie , Poulet Emmanuel , Chauliac Nicolas , Cuvillier Bruno
Published: December 2019

Aim

Patient suicide (PS) has been identified as a frequent and stressful “occupational hazard” for mental health professionals. Studies are needed to assess the impact on psychiatric trainees of the exposure to severe patient suicidal behaviours.

Methods

Our cross‐sectional study aimed to measure the prevalence of exposure to PS and severe patient suicide attempts (SPSA) in French psychiatric trainees. We also assessed the emotional, traumatic and professional impacts and perceived support in the aftermath through a 62‐item online questionnaire that included the French version of the IES‐R, a composite emotional score and questions about professional practice and perceived support. All French psychiatric trainees were contacted regarding participation in the study through email and social networks between November 2017 and March 2018.

Results

A total of 409 trainees participated in the survey (response rate = 16.4%). 253 trainees fully completed the questionnaire. Of the 253 trainees, 43.2% were exposed to PS and 13.8% to SPSA. The exposure mostly occurred in the early stage of the training period. Ten to 15% of exposed trainees showed a high level of traumatic and emotional impact and 8.1% exhibited clinically relevant symptoms of post‐traumatic stress disorder (PTSD). We found that 21.6% received no support in the aftermath, especially after PS.

Conclusion

A large proportion of psychiatric trainees encounter severe suicidal behaviours of patients, and a substantial part of them is highly impacted. Our results thus stress the need for programmes dedicated to the prevention of the deleterious effects of the exposure to PS or SPSA in psychiatric trainees.
What predicts quality of life after subthalamic deep brain stimulation in Parkinson’s disease? A systematic review
Authors: Geraedts V. J. , Feleus S. , Marinus J. , van Hilten J. J. , Contarino M. F.
Published: December 2019

Background and purpose

Subthalamic deep brain stimulation (STN DBS) is an effective therapy against medication‐refractory motor complications in patients with Parkinson’s disease. However, it remains difficult to predict which baseline patient characteristics are associated with quality of life (QoL) after surgery. The objective was to identify preoperative factors associated with QoL after STN DBS by systematically reviewing publications of sufficient methodological quality.

Methods

Main databases were systematically searched up to March 2019 to identify studies that investigated factors associated with QoL after STN DBS in patients with idiopathic Parkinson’s disease.

Results

In all, 869 studies were identified, of which 18 fulfilled the inclusion criteria. Higher QoL after DBS appears to be associated with a large preoperative difference between ON and OFF motor function in some studies, although there was no clear association of severity of motor function or motor complications with postoperative QoL. Lower severity of dyskinesias was associated with greater postoperative QoL improvement but has been insufficiently studied. Higher baseline QoL was suggestive of higher postoperative QoL. Four studies suggested that older age at surgery is associated with a lower improvement, although six other studies reported no association. No or limited evidence was found for cognitive impairment or psychiatric dysfunction.

Conclusion

Various relative contraindications for STN DBS such as cognitive impairment and psychiatric dysfunction appear to be unrelated to postoperative QoL. However, the lack of clear correlations with disease‐related variables suggests that QoL may be individually influenced by other factors, indicating that an ideal preoperative patient profile with regard to QoL improvement cannot be readily provided.
Management of bladder rupture in mature horses
Authors: Peitzmeier M. D. , Slone D. E.
Published: December 2019

Rupture of the urinary bladder of adult horses is rare with both reports of surgical repair and conservative management in the literature. The case report by Goslinget al. in this issue describes the successful treatment of an iatrogenic bladder tear in an adult gelding. The aim of this commentary is to review the described treatment options.
Surgical treatment of a complicated distal tibia epiphyseal Salter–Harris type I fracture in a yearling
Authors: Noguera Cender A. C. , Lischer C. J. , Mählmann K.
Published: December 2019

This article describes the management of a complicated distal epiphyseal Salter–Harris type I fracture of the left tibia in a yearling horse. Closed reduction and internal fixation was attempted in the first surgery using tension band wires. Due to fracture instability 2 weeks after surgery, a full‐limb transfixation pin cast was applied to the tibia and maintained for 7 weeks to prevent further fracture displacement and to achieve axial alignment. The full‐limb cast was maintained for a total of 12 weeks, including the time with the transfixation pin cast. Cast sores and tendon laxity resolved without further complications. Ten months after the first surgery, the fracture had radiographically healed, and the horse was sound at the walk and trot in a straight line.