bluuebunny/crossref_metadata_2025 huggingface dataset:
Cue identification in phenology: A case study of the predictive performance of current statistical tools
Authors: Simmonds Emily G. , Cole Ella F. , Sheldon Ben C.
Published: June 2019

Changes in the timing of life‐history events (phenology) are a widespread consequence of climate change. Predicting population resilience requires knowledge of how phenology is likely to change over time, which can be gained by identifying the specific environmental cues that drive phenological events. Cue identification is often achieved with statistical testing of candidate cues. As the number of methods used to generate predictions increases, assessing the predictive accuracy of different approaches has become necessary.

This study aims to (a) provide an empirical illustration of the predictive ability of five commonly applied statistical methods for cue identification (absolute and relative sliding time window analyses, penalized signal regression, climate sensitivity profiles and a growing degree‐day model) and (b) discuss approaches for implementing cue identification methods in different systems.

Using a dataset of mean clutch initiation timing in wild great tits (Parus major), we explored how the days of the year identified as most important, and the aggregate statistic identified as a cue, differed between statistical methods and with respect to the time span of data used. Each method's predictive capacity was tested using cross‐validation and assessed for robustness to varying sample size.

We show that the identified critical time window of cue sensitivity was consistent across four of the five methods. The accuracy and precision of predictions differed by method with penalized signal regression resulting in the most accurate and most precise predictions in our case. Accuracy was maximal for near‐future predictions and showed a relationship with time. The difference between predictions and observations systematically shifted across the study from preceding observations to lagging.

This temporal trend in prediction error suggests that the current statistical tools either fail to capture a key component of the cue–phenology relationship, or the relationship itself is changing through time in our system. These two influences need to be teased apart if we are to generate realistic predictions of phenological change. We recommend future phenological studies to challenge the idea of a static cue–phenology relationship and should cross‐validate results across multiple time periods.
The contribution of spatial mass effects to plant diversity in arable fields
Authors: Metcalfe Helen , Hassall Kirsty L. , Boinot Sébastien , Storkey Jonathan
Published: June 2019

In arable fields, plant species richness consistently increases at field edges. This potentially makes the field edge an important habitat for the conservation of the ruderal arable flora (or ‘weeds’) and the invertebrates and birds it supports. Increased diversity and abundance of weeds in crop edges could be owing to either a reduction in agricultural inputs towards the field edge and/or spatial mass effects associated with dispersal from the surrounding landscape.

We contend that the diversity of weed species in an arable field is a combination of resident species, that can persist under the intense selection pressure of regular cultivation and agrochemical inputs (typically more ruderal species), and transient species that rely on regular dispersal from neighbouring habitats (characterised by a more ‘competitive’ ecological strategy).

We analysed a large dataset of conventionally managed arable fields in the UK to study the effect of the immediate landscape on in‐field plant diversity and abundance and to quantify the contribution of spatial mass effects to plant diversity in arable fields in the context of the ecological strategy of the resulting community.

We demonstrated that the decline in diversity with distance into an arable field is highly dependent on the immediate landscape, indicating the important role of spatial mass effects in explaining the increased species richness at field edges in conventionally managed fields.

We observed an increase in the proportion of typical arable weeds away from the field edge towards the centre. This increase was dependent on the immediate landscape and was associated with a higher proportion of more competitive species, with a lower fidelity to arable habitats, at the field edge.

Synthesis and applications. Conserving the ruderal arable plant community, and the invertebrates and birds that use it as a resource, in conventionally managed arable fields typically relies on the targeted reduction of fertilisers and herbicides in so‐called ‘conservation headlands’. The success of these options will depend on the neighbouring habitat and boundary. They should be placed along margins where the potential for ingress of competitive species, that may become dominant in the absence of herbicides, is limited. This will enhance ecosystem services delivered by the ruderal flora and reduce the risk of competitive species occurring in the crop.
Large‐scale manipulation of the acoustic environment can alter the abundance of breeding birds: Evidence from a phantom natural gas field
Authors: Cinto Mejia Elizeth , McClure Christopher J. W. , Barber Jesse R.
Published: June 2019

Altered animal distributions are a consequence of human expansion and development. Anthropogenic noise can be an important predictor of abundance declines near human infrastructure, yet more information is needed to understand noise impacts at the spatial and temporal scales necessary to alter populations.

Energy development and associated anthropogenic noise are globally pervasive, and expanding. For example, 600,000 new natural gas wells have been drilled across central North America in less than 20 years.

We experimentally broadcast energy sector noise (recordings of compressor engines) in Southwest Idaho (USA). We placed arrays of speakers creating a ‘phantom natural gas field' in a large‐scale experiment and tested the effects of noise alone on breeding songbird abundance. To examine variation in human‐caused noise, we broadcast two types of compressor noise, one with a slightly higher sound intensity and greater bandwidth than the other.

Our phantom natural gas field encompassed approximately 100 km2. We broadcast noise over three continuous months, for each of two seasons, and quantified over 20,000 hr of background sound levels.

Brewer's sparrows (Spizella breweri) were affected by our narrowband playback, declining 30%, 50 m from the speaker arrays. During our broadband playback, all species combined and Brewer's sparrows decreased 20% and 33%, respectively, at the scale of our sites (~0.5 km2; up to 400 m from speaker arrays).

Synthesis and applications. Our results show the importance of incorporating the acoustic structure of noise when estimating the cost of noise exposure for populations. We suggest an urgent need for noise mitigation, such as quieting compressor stations, in energy extraction fields and other sources in natural areas broadly.
Practical Empirical Research Using gretl and hansl
Authors: Tarassow Artur
Published: June 2019

This article provides an introduction to the free open‐source statistics and econometrics software gretl. The software is an attempt to bridge the different demands for teaching at different levels. Furthermore, it also provides functionalities required for professional work. We also introduce gretl's powerful and intuitive scripting language ‘hansl’. This article can be seen as an illustrated step‐by‐step guide that uses a real‐life data analysis example. Finally, I estimate a vector autoregressive time‐series model using gretl for structural analyses as well as for forecasting purposes.
Distributing Student Places in Australian Higher Education
Authors: Norton Andrew
Published: June 2019

Higher education systems need policies for distributing student places between higher education providers, courses and students. In supply‐driven systems, government and university decisions dominate. In demand‐driven systems, student choices play a larger role. Over the last 35 years Australia has moved from a supply‐driven to a largely demand‐driven university system and then partly back again. When students pay their own costs, both major political parties have supported market distribution of student places for decades. But for subsidised student places there is policy instability, due to fluctuating priorities for containing public expenditure and responding to demographic and labour market changes.
Causative alternations in Siraiki
Authors: Lowe John J. , Birahimani Ali H.
Published: June 2019

Siraiki is a major but understudied Indo‐Aryan language spoken mainly in central Pakistan. Its causative system, which has never been described in detail, shows many similarities with causative systems in related modern Indo‐Aryan languages, but also differences which render it unique within this family. We provide a detailed account of causativization in Siraiki, and attempt to explain the synchronic complexity of the Siraiki data, as well as the broader variation within modern Indo‐Aryan, in diachronic terms.
Financialization, Urban Governance and the Planning System: Utilizing ‘Development Viability’ as a Policy Narrative for the Liberalization of Ireland's Post‐Crash Planning System
Authors: Waldron Richard
Published: June 2019

Drawing upon the Irish case, this article explores the interaction between the financialized economy and the urban planning system. While considerable scholarship has examined the financialization of real estate, it remains unclear how planning systems are being repurposed to facilitate a finance‐led regime of urban growth or how the ‘real estate–financial complex’ seeks to enact planning policy transformations that support its interests. This article explores how such actors have advanced the concept of ‘financial viability of development’ as a means of influencing the post‐crisis re‐regulation of Irish planning policy. This group has argued that housing construction in post‐crash Ireland is unviable given the high development finance costs, onerous planning gain contributions and the lack of development certainty in the planning process. As such, housing construction has been at an all‐time‐low, leading to a new crisis in affordable housing provision. In response, a complicit state has further liberalized the planning system, introducing an array of policies that are evermore facilitative of development interests. Empirical findings, based on interviews with developers, lobbyists and planners, emphasize the importance of informal access to policymakers, the wielding of ‘expert knowledge’ and media management to co‐opt the state into adopting financial viability within planning policymaking.
Are minorities free riders? Applying the social resistance framework to public goods production in Central‐Eastern Europe
Authors: LETKI NATALIA , KUKOŁOWICZ PAULA
Published: June 2019

One of the key reasons for the scholarly and policy concern about the rising levels of ethnic diversity is its apparently detrimental effect on the production of public goods. Although numerous studies have tackled that issue, there is still much ambiguity as to the precise micro‐level mechanisms underpinning this relationship. In this article, a novel theoretical explanation for this relationship is proposed, building on the social resistance framework. This proposition is tested using a new cross‐sectional public opinion survey covering 14,536 respondents in 817 neighbourhoods across 11 Central Eastern European countries. Analysing national minorities defined by postwar border changes means one can overcome the endogeneity problem faced by research based on immigrant groups. The findings show that it is the combination of a minority group's discrimination and its spatial clustering that makes minorities reluctant to contribute to public goods. The article constitutes a novel theoretical and methodological contribution to the research on the effects of diversity on public goods provision.
Multi‐Site Bundling of Drought Tolerant Maize Varieties and Index Insurance
Authors: Awondo Sebastain N. , Kostandini Genti , Setimela Peter , Erenstein Olaf
Published: June 2019

Drought Tolerant Maize Varieties (DTMV) and Rainfall Index Insurance (RII) are potential complements, though with limited empirical basis. We employ a multivariate spatial framework to investigate the potential for bundling DTMV with a simulated multi‐site and multi‐environment RII, designed to insure against mild, moderate and severe drought risk. We use yield data from on‐farm trials conducted by the International Maize and Wheat Improvement Center (CIMMYT) and partners over 49 locations in Eastern and Southern Africa spanning 8 countries and 5 mega‐environments (dry lowland, dry mid altitude, wet lower mid altitude, low wetland and wet upper mid altitude) in which 19 different improved maize varieties including DTMV were tested at each location. Spatially correlated daily rainfall data are generated from a first‐order two‐state Markov chain process and used to calibrate the index and predict yields with a hierarchical Bayes multivariate spatial model. Results show high variation in the performance and benefits of different bundles which depend on the maize variety, the risk layer insured, and the type of environment, with high chances of selecting a sub‐optimal and unattractive contract. We find that complementing RII with a specific DTMV produces contracts with lower premiums and higher guaranteed returns especially in dry lowland increasing the chances of scaling up RII within this environment.
Rethinking the Mechanism of the Health Benefits of Proanthocyanidins: Absorption, Metabolism, and Interaction with Gut Microbiota
Authors: Tao Wenyang , Zhang Yu , Shen Xuemin , Cao Yanping , Shi John , Ye Xingqian , Chen Shiguo
Published: June 2019

Proanthocyanidins, as the oligomers or polymers of flavan‐3‐ol, are widely discovered in plants such as fruits, vegetables, cereals, nuts, and leaves, presenting a major part of dietary polyphenols. Although proanthocyanidins exert several types of bioactivities, such as antioxidant, antimicrobial, cardioprotective, and neuroprotective activity, their exact mechanisms remain unclear. Due to the complexity of the structure of proanthocyanidins, such as their various monomers, different linkages and isomers, investigation of their bioavailability and metabolism is limited, which further hinders the explanation of their bioactivities. Since the large molecular weight and degree of polymerization limit the bioavailability of proanthocyanidins, the major effective site of proanthocyanidins is proposed to be in the gut. Many studies have revealed the effects of proanthocyanidins from different sources on changing the composition of gut microbiota based on in vitro and in vivo models and the bioactivities of their metabolites. However, the metabolic routes of proanthocyanidins by gut microbiota and their mutual interactions are still sparse. Thus, this review summarizes the chemistry, absorption, and metabolic pathways of proanthocyanidins ranging from monomers to polymers, as well as the mutual interactions between proanthocyanidins and gut microbiota, in order to better understand how proanthocyanidins exert their health‐promoting functions.
Brown Rice Versus White Rice: Nutritional Quality, Potential Health Benefits, Development of Food Products, and Preservation Technologies
Authors: Saleh Ahmed S. M. , Wang Peng , Wang Na , Yang Liu , Xiao Zhigang
Published: June 2019

Obesity and chronic diet‐related diseases such as type 2 diabetes, hypertension, cardiovascular disease, cancers, and celiac are increasing worldwide. The increasing prevalence of these diseases has led nutritionists and food scientists to pay more attention to the relationship between diet and different disease risks. Among different foods, rice has received increasing attention because it is a major component of billions of peoples’ diets throughout the world. Rice is commonly consumed after polishing or whitening and the polished grain is known a high glycemic food because of its high starch content. In addition, the removal of the outer bran layer during rice milling results in a loss of nutrients, dietary fiber, and bioactive components. Therefore, many studies were performed to investigate the potential health benefits for the consumption of whole brown rice (BR) grain in comparison to the milled or white rice (WR). The objective of this work was to review the recent advances in research performed for purposes of evaluation of nutritional value and potential health benefits of the whole BR grain. Studies carried out for purposes of developing BR‐based food products are reviewed. BR safety and preservation treatments are also explored. In addition, economic and environmental benefits for the consumption of whole BR instead of the polished or WR are presented. Furthermore, challenges facing the commercialization of BR and future perspectives to promote its utilization as food are discussed.
Decontamination of Microorganisms and Pesticides from Fresh Fruits and Vegetables: A Comprehensive Review from Common Household Processes to Modern Techniques
Authors: Bhilwadikar Tanmayee , Pounraj Saranya , Manivannan S. , Rastogi N. K. , Negi P. S.
Published: June 2019

Fresh fruits and vegetables are a rich source of micronutrients. However, many foodborne illnesses have been linked to the consumption of fresh fruits and vegetables as they are reported to harbor contaminants such as microorganisms and pesticides. Recently reported foodborne outbreaks have been linked to a diverse group of fruits and vegetables due to the presence of various pathogens including Salmonella, Escherichia coli, and Listeria monocytogenes. Also, the increased use of pesticides has resulted in the deposition of chemical residues on the surface of fruits and vegetables, which has led to the adverse health conditions such as cancer, birth defects, and neurodevelopmental disorders. Fresh commodities are subjected to various treatments to prevent or minimize these outbreaks, and the main targets of such treatments have been the elimination of pathogens and degradation of toxic chemical residues. Here, we have discussed various decontamination methods including simple household washing, chemical treatments, and modern technologies with their mode of action for microbial and pesticide removal. The simple household processes are not very effective in the removal of pathogenic organisms and pesticides. The use of modern techniques like cold plasma, ozone, high hydrostatic pressure, and so on, showed better efficacy in the removal of microorganisms and pesticides. However, their industrial use is limited considering high installation and maintenance cost. In this review, we suggest combined methods based on their mode of decontamination and suitability for a selected fruit or vegetable for effective decontamination of microbes and pesticide together to reduce the treatment cost and enhance food safety.
Unprocessed red meat intakes are associated with increased inflammation, triglycerides and HDL cholesterol in past smokers
Authors: Wu Tianying , Sonoda Samantha , Liu Hongxia
Published: June 2019

Aim

To determine the associations of unprocessed red meat with serum C‐reactive protein and traditional lipid biomarkers among adults with different smoking status.

Methods

Using a cross‐sectional design, we analysed data collected from 5011 adults (men and women) who had provided information on dietary intakes and the proposed biomarkers for the 2005–2006 National Health and Nutrition Examination Survey (NHANES).

Results

We found positive associations between unprocessed red meat and serum C‐reactive protein and triglycerides and an inverse association between unprocessed red meat and high‐density lipoprotein (HDL) cholesterol in past smokers, but no associations in never smokers and current smokers. Among past smokers, the percent difference of biomarkers between participants with the highest and the lowest quintiles for the intakes of unprocessed red meat was 42% (P = 0.03) for CRP, 32% for triglycerides and −11% (P = 0.02) for HDL cholesterol. No association was found between unprocessed red meat and other lipid biomarkers.

Conclusions

Providing individualised nutritional guidelines according to smoking status is important. Our study provided evidence for developing specific guidelines on red meat for past smokers.
Protocols for yTREX/Tn5‐based gene cluster expression in Pseudomonas putida
Authors: Weihmann Robin , Domröse Andreas , Drepper Thomas , Jaeger Karl‐Erich , Loeschcke Anita
Published: June 2019

Bacterial gene clusters, which represent a genetic treasure trove for secondary metabolite pathways, often need to be activated in a heterologous host to access the valuable biosynthetic products. We provide here a detailed protocol for the application of the yTREX ‘gene cluster transplantation tool’: Via yeast recombinational cloning, a gene cluster of interest can be cloned in the yTREX vector, which enables the robust conjugational transfer of the gene cluster to bacteria like Pseudomonas putida, and their subsequent transposon Tn5‐based insertion into the host chromosome. Depending on the gene cluster architecture and chromosomal insertion site, the respective pathway genes can be transcribed effectively from a chromosomal promoter, thereby enabling the biosynthesis of a natural product. We describe workflows for the design of a gene cluster expression cassette, cloning of the cassette in the yTREX vector by yeast recombineering, and subsequent transfer and expression in P. putida. As an example for yTREX‐based transplantation of a natural product biosynthesis, we provide details on the cloning and activation of the phenazine‐1‐carboxylic acid biosynthetic genes from Pseudomonas aeruginosa in P. putidaKT2440 as well as the use of β‐galactosidase‐encoding lacZ as a reporter of production levels.
Non‐invasive, ratiometric determination of intracellular pH in Pseudomonas species using a novel genetically encoded indicator
Authors: Arce‐Rodríguez Alejandro , Volke Daniel C. , Bense Sarina , Häussler Susanne , Nikel Pablo I.
Published: June 2019

The ability of Pseudomonas species to thrive in all major natural environments (i.e. terrestrial, freshwater and marine) is based on its exceptional capability to adapt to physicochemical changes. Thus, environmental bacteria have to tightly control the maintenance of numerous physiological traits across different conditions. The intracellular pH (pHi) homoeostasis is a particularly important feature, since the pHi influences a large portion of the biochemical processes in the cell. Despite its importance, relatively few reliable, easy‐to‐implement tools have been designed for quantifying in vivo pHi changes in Gram‐negative bacteria with minimal manipulations. Here we describe a convenient, non‐invasive protocol for the quantification of the pHi in bacteria, which is based on the ratiometric fluorescent indicator protein PHP (pH indicator for Pseudomonas). The DNA sequence encoding PHP was thoroughly adapted to guarantee optimal transcription and translation of the indicator in Pseudomonas species. Our PHP‐based quantification method demonstrated that pHi is tightly regulated over a narrow range of pH values not only in Pseudomonas, but also in other Gram‐negative bacterial species such as Escherichia coli. The maintenance of the cytoplasmic pH homoeostasis in vivo could also be observed upon internal (e.g. redirection of glucose consumption pathways in P. putida) and external (e.g. antibiotic exposure in P. aeruginosa) perturbations, and the PHP indicator was also used to follow dynamic changes in the pHi upon external pH shifts. In summary, our work describes a reliable method for measuring pHi in Pseudomonas, allowing for the detailed investigation of bacterial pHi homoeostasis and its regulation.
The prognostic value of the preoperative albumin to alkaline phosphatase ratio in patients with non‐small cell lung cancer after surgery
Authors: Zhang Lianmin , Zhang Hua , Yue Dongsheng , Wei Wei , Chen Yulong , Zhao Xiaoliang , Zhu Jianquan , Zhang Bin , Zhang Zhenfa , Wang Changli
Published: June 2019

Background

To assess the potential prognostic value of the albumin to alkaline phosphatase ratio (AAPR) in patients with non‐small cell lung cancer (NSCLC) after surgery.

Methods

The log‐rank and Kaplan‐Meier analyses were performed to detect differences in survival levels between different groups. A model of Cox proportional hazards was used to perform univariate and multivariate survival analyses. Comparisons of receiver operating characteristic (ROC) curves and the likelihood ratio test (LRT) were also utilized to compare the prognostic abilities of different systems for overall survival (OS) prediction.

Results

The optimal cut‐off value of the preoperative AAPR was 0.64. A decreased AAPR was associated with several clinicopathological and clinicolaboratory variables related to cancer progression. The preoperative AAPR of patients was positively correlated with the poor prognosis of NSCLC. In multivariate analyses, the preoperative AAPR was identified as an independent prognostic factor for disease‐free survival (DFS; P = 0.001) and overall survival (OS; P = 0.003). The LRT showed that the AAPR tumor‐node‐metastasis (TNM) system presented a significantly larger χ2 value (112.4 vs. 89.2, respectively, P < 0.01) and a relatively smaller Akaike information criterion (AIC) value (2955 vs. 2977, respectively, P < 0.01) than the TNM staging system.

Conclusion

Preoperative AAPR was a potentially valuable prognostic factor in NSCLC patients who underwent surgery. Our results further showed that the AAPR‐TNM system was superior to the current TNM staging system.
The pharmacological reduction of hippocampal neurogenesis attenuates the protective effects of cannabidiol on cocaine voluntary intake
Authors: Luján Miguel Ángel , Cantacorps Lídia , Valverde Olga
Published: June 2019

The administration of cannabidiol has shown promising evidence in the treatment of some neuropsychiatric disorders, including cocaine addiction. However, little information is available as to the mechanisms by which cannabidiol reduces drug use and compulsive seeking. We investigated the role of adult hippocampal neurogenesis in reducing cocaine voluntary intake produced by repeated cannabidiol treatment in mice. Cocaine intake was modelled using the intravenous cocaine self‐administration procedure in CD1 male mice. Cannabidiol (20 mg/kg) reduced cocaine self‐administration behaviour acquisition and total cocaine intake and enhanced adult hippocampal neurogenesis. Our results show that a 6‐day repeated temozolomide treatment (25 mg/kg/day), a chemotherapy drug that blocks hippocampal neurogenesis, prevented cannabidiol‐induced increment in the early stages of neuronal maturation and differentiation, without altering the basal levels of BrdU/NeuN and doublecortin immunostaining. The reduction of total cocaine intake and operant behaviour acquisition observed following cannabidiol exposure was attenuated by temozolomide treatment. Our results also show a similar effect of temozolamide on a cannabidiol‐induced improvement of novel object recognition memory, a task influenced by the proneurogenic effects of cannabidiol (10 and 20 mg/kg). The anxiolytic effects of cannabidiol (10 and 20 mg/kg), however, remained unaffected after its proneurogenic effects decreased. The present study confirms that adult hippocampal neurogenesis is one of the mechanisms by which cannabidiol lowers cocaine reinforcement and demonstrates the functional implication of adult hippocampal neurogenesis in cocaine voluntary consumption in mice. Such findings highlight the possible use of cannabidiol for developing new pharmacotherapies to manage cocaine use disorders.
Long‐term effects of repeated fuel‐reduction burning and logging on bats in south‐eastern Australia
Authors: Law Bradley , Kathuria Amrit , Chidel Mark , Brassil Traecey
Published: June 2019

Fire regimes have a major influence on biodiversity in many ecosystems around the globe, yet our understanding of the longer‐term response of fauna is typically poor. We sampled bats with ultrasonic detectors in three different years in dry sclerophyll forests of south‐eastern Australia in a long‐term, management‐scale experiment. Frequent low‐intensity burning (every 2 or 4 years plus unburnt) and logging (with 33% retention of the original unlogged tree basal area) were manipulated to assess their effects on bats. We found that both the fire regime and regrowth after logging influenced the local bat community. The routine burning treatment (burnt every 4 years) in unlogged forest was consistently related to higher total bat activity (2–3 times) and species richness when compared to unburnt controls and logging treatments. Foraging activity was more variable, but it was typically lowest in Unlogged Unburnt Controls. These patterns were evident at both the detector site scale and the block scale and were probably due to a reduction in understorey stem density with burning, especially in unlogged forest. Bat activity was significantly lower across the entire study area (including controls) in 1 year, when sampling occurred within 6 months of burning. When pooled across burning treatments, unlogged forest supported higher bat activity (1.5 times) and species richness than logged forest (12‐ to 17‐year‐old regrowth), again most likely because of a negative association with high stem density in regrowth after logging. We conclude that low‐intensity burning had positive benefits for echolocating bats, most notably in unlogged forest. However, careful planning is required to generate heterogeneous vegetation patterns that are likely to be most suitable for a range of taxa.
Influences on general practitioner referral to allied health professionals for fall prevention in primary care
Authors: Liddle Jeannine , Clemson Lindy , Mackenzie Lynette , Lovarini Meryl , Tan Amy , Pit Sabrina W. , Roberts Chris , Tiedemann Anne , Sherrington Cathie , Willis Karen
Published: June 2019

Objective

To explore influences on referral for fall prevention from general practitioners (GPs) to allied health professionals (AHPs) to better equip AHPs engage with GPs regarding fall prevention.

Methods

Qualitative, semi‐structured interviews with GPs (n = 24), practice nurses (n = 3) and AHPs (n = 15) and field notes were analysed inductively using constant comparative methods.

Results

Three main themes regarding influences on GP referral to AHPs for fall prevention were identified as follows: GPs' knowledge of AHPs; The “reliable and good” AHP; and Patient feedback‐Patient choice. Three‐way communication and trust between GP, patient and AHP underpinned each of these themes.

Conclusions

Strategies for encouraging GP referral include AHPs personally contacting GPs to explain their services; writing to GPs about every patient seen; and being aware that interprofessional relationships are based on trust and take time to develop. GPs and AHPs are encouraged to communicate directly rather than relying on patients to convey verbal information.
Ranging behaviour of Uganda’s elephants
Authors: Grogan James , Plumptre Andrew , Mabonga Joshua , Nampindo Simon , Nsubuga Mustapha , Balmford Andrew
Published: June 2019

Elephant populations are in decline across the African continent, but recent aerial surveys show that populations in Uganda are increasing. However, threats such as poaching and habitat disturbance remain. Having a comprehensive knowledge of the ranging behaviour of Ugandan elephants is crucial to understanding where critical habitat for the species occurs. We investigated various aspects of ranging behaviour of 45 radio‐collared elephants (Loxodonta africana) in three areas—Queen Elizabeth Protected Area (QEPA), Murchison Falls (MFPA) Protected Area and Kidepo Valley (KVCA) Conservation Area. We also set Ugandan analyses in a continental context by comparison with home ranges reported in published literature. Elephants within KVCA had larger core ranges than elephants in QEPA or MFPA. Wet season ranges in KVCA were much larger than dry season ranges. The most important core areas in all three national parks were centred around water resources. Home range size was negatively correlated with net primary productivity (NPP) at Ugandan (N = 39 individuals) and continental (N = 17 sites) scales. This study indicates that, at a local scale, factors such as water source location are important in shaping elephant ranging behaviour. At larger scales, factors such as NPP are good predictors of elephant home range size.
The design and evaluation of a novel low‐cost portable ventilator
Authors: Darwood A. , McCanny J. , Kwasnicki R. , Martin B. , Jones P.
Published: June 2019

Modern mechanical ventilator technologies broadly consist of digitally‐controlled electronic devices and analogue systems driven by compressed gas sources. Drawbacks such as high cost, complex maintenance and the need for cumbersome sources of compressed driving gas hinder adoption in pre‐hospital and low‐resource environments. We describe the evaluation and testing of a simple, low‐cost alternative ventilator that uses a novel pressure‐sensing approach and control algorithm. This is designed to provide portable positive‐pressure mechanical ventilation at a reduced cost, while autonomously monitoring patient condition and important safety parameters. A prototype ventilator was constructed and evaluated using an anaesthetic test‐lung as a patient surrogate. Using a modifiable test‐lung and digital pressure sensor, we investigated ventilation pressure waveform circuit leak detection, and compliance and resistance change detection. During intermittent positive‐pressure ventilation to the test‐lung, the prototype system showed acceptable pressure waveform parameters: all simulated circuit leaks ≥ 6 mm2 in size were detected; compliance changes were detected between 10 ml.cmH2O−1, 20 ml.cmH2O−1 and 50 ml.cmH2O−1; and resistance changes were detected across the available simulated range. These results show this prototype technology has the potential to provide safe emergency ventilation without the use of any complex digital sensors or software while its construction and design enables significant reductions in cost and complexity. The study suggests further work is now justified in progressing the technology to clinical trials.
Proteins adsorbed to a polysulfone hemodialysis membrane under heparin and citrate anticoagulation regimens
Authors: Mares Jan , Tuma Zdenek , Moravec Jiri , Pavlina Richtrova , Matejovic Martin
Published: June 2019

The study aim was to compare molecular‐level effects (blood‐dialyzer interactions) of heparin and citrate anticoagulation using proteome‐wide analysis of biofilm adsorbed to dialysis membrane. Ten patients receiving maintenance hemodialysis were examined in a crossover design under three different anticoagulation regimens, namely citrate, heparin, and anticoagulation‐free (control). Following a regular hemodialysis session (4 hours, polysulfone membrane), dialyzers were flushed and the surface biofilm eluted by acetic acid. Protein composition of the eluates was determined by 2‐dimensional gel electrophoresis and resulting patterns compared between regimens. Proteins responsible for the difference were identified by mass spectrometry. Citrate anticoagulation was associated with significantly less protein adsorption to the membrane than heparin (2.2 [1.1‐2.9] mg vs. 6.5 [2.9‐11.6] mg, P = 0.009). Among the proteins identified as major discriminators between citrate and the other regimens, fibrin α‐chain fragments of molecular weight below 40 kDa prevailed. In these fragments, an analysis of the amino acid sequence has been performed by comparison with the UniProt database. It showed missing α‐chain cross‐links. On the contrary, heparin prevented adsorption and cleavage of several heparin‐binding proteins; especially complement factor H‐related protein 3, insulin‐like growth factor binding proteins (2, 4, and 5), and chemerin. Compared to heparin, citrate is associated with less protein adsorption and imperfectly crosslinked fibrin clot formation. Membrane adsorptive properties are significantly modified by the anticoagulation regimen.
The moderating role of interviewer's regulatory focus in the effectiveness of impression management tactics: Regulatory fit as a source of subjective value
Authors: Bian Ran , Sun Fuzhuo , Lin Zheting , Gao Qin , Yuan Xiaoxiao , Xie Aishan
Published: June 2019

Based on the recently explored regulatory fit effect in social contexts, the present research is the first to investigate the interaction between interviewer's regulatory focus and interviewee's impression management (IM) tactics. We hypothesized that assertive and defensive IM tactics would fit with interviewer's promotion and prevention focus, respectively, and that interviewer's experience of this regulatory fit would lead to enhanced interview evaluation. We conducted four studies in which the participants were asked to rate an interviewee after reading a list of the interviewee's IM‐related behaviours or watching a videotaped interview. Additionally, the participant's regulatory focus was operationalized as both an induced situational state and a measured chronic trait. The results supported our hypotheses by showing a significant interaction of the interviewer's regulatory focus and the IM tactics on interview evaluation: the promotion‐assertive and the prevention‐defensive ratings were more positive than the prevention‐assertive and the promotion‐defensive ratings. Moreover, mediation analysis revealed that the interaction exerts its effects on interview evaluation by providing interviewers with an intrapersonal regulatory fit experience.
Inhibition of polycomb repressor complex 2 ameliorates neointimal hyperplasia by suppressing trimethylation of H3K27 in vascular smooth muscle cells
Authors: Liang Jing , Li Qi , Cai Wenbin , Zhang Xuejiao , Yang Bing , Li Xin , Jiang Shuai , Tian Shanshan , Zhang Kai , Song Hao , Ai Ding , Zhang Xu , Wang Chunjiong , Zhu Yi
Published: June 2019

Background and Purpose

The increased proliferation and migration of vascular smooth muscle cells (VSMCs) after arterial injury contributes greatly to the pathogenesis of neointimal hyperplasia. As a major component of epigenetics, histone methylation plays an important role in several cardiovascular diseases. However, its role in restenosis is still unclear.

Experimental Approach

Human aortic VSMCs were challenged with PDGF‐BB, and total histones were extracted and analysed by HPLC/MS. For the in vivo study, rats were subjected to wire‐guided common carotid injury.

Key Results

PDGF‐BB markedly increased the H3K27me3 level, as demonstrated by use of HPLC/MS and confirmed by western blot analysis. Enhancer of zeste homologue 2 (EZH2), the histone H3K27 methyltransferase component of polycomb repressive complex 2, was also up‐regulated by PDGF‐BB in VSMCs, and in the neointimal hyperplasia induced by wire injury of the rat carotid artery. Furthermore, inhibiting H3K27me3 by treatment with 3‐μM UNC1999, an EZH2/1 inhibitor, significantly suppressed PDGF‐BB‐induced VSMC proliferation compared with the PDGF‐BB‐treated group. Consistently, neointimal formation was significantly attenuated by oral or perivascular administration of UNC1999 compared with the sham group. Mechanistically, the increase in H3K27me3 inhibited the transcription of the cyclin‐dependent kinase inhibitor p16INK4A and thus promoted VSMC proliferation.

Conclusions and Implications

Vascular injury elevated the expression of EZH2 and the downstream target H3K27me3, which suppressed p16INK4A expression in VSMCs and promoted VSMC proliferation and neointimal hyperplasia. EZH2 inhibition might be a potential therapeutic target for restenosis.
Comparison of the ligand‐binding properties of fluorescent VEGF‐A isoforms to VEGF receptor 2 in living cells and membrane preparations using NanoBRET
Authors: Peach Chloe J. , Kilpatrick Laura E. , Woolard Jeanette , Hill Stephen J.
Published: June 2019

Background and Purpose

Vascular endothelial growth factor A (VEGF‐A) is a key mediator of angiogenesis. A striking feature of the binding of a fluorescent analogue of VEGF165a to nanoluciferase‐tagged VEGF receptor 2 (VEGFR2) in living cells is that the BRET signal is not sustained and declines over time. This may be secondary to receptor internalisation. Here, we have compared the binding of three fluorescent VEGF‐A isoforms to VEGFR2 in cells and isolated membrane preparations.

Experimental Approach

Ligand‐binding kinetics were monitored in both intact HEK293T cells and membranes (expressing nanoluciferase‐tagged VEGFR2) using BRET between tagged receptor and fluorescent analogues of VEGF165a, VEGF165b, and VEGF121a. VEGFR2 endocytosis in intact cells expressing VEGFR2 was monitored by following the appearance of fluorescent ligand‐associated receptors in intracellular endosomes using automated quantitative imaging.

Key Results

Quantitative analysis of the effect of fluorescent VEGF‐A isoforms on VEGFR2 endocytosis in cells demonstrated that they produce a rapid and potent translocation of ligand‐bound VEGFR2 into intracellular endosomes. NanoBRET can be used to monitor the kinetics of the binding of fluorescent VEGF‐A isoforms to VEGFR2. In isolated membrane preparations, ligand‐binding association curves were maintained for the duration of the 90‐min experiment. Measurement of the koff at pH 6.0 in membrane preparations indicated shorter ligand residence times than those obtained at pH 7.4.

Conclusions and Implications

These studies suggest that rapid VEGF‐A isoform‐induced receptor endocytosis shortens agonist residence times on the receptor (1/koff) as VEGFR2 moves from the plasma membrane to the intracellular endosomes.
Acquired resistance mechanisms to afatinib in HER2‐amplified gastric cancer cells
Authors: Yoshioka Takahiro , Shien Kazuhiko , Takeda Tatsuaki , Takahashi Yuta , Kurihara Eisuke , Ogoshi Yusuke , Namba Kei , Torigoe Hidejiro , Sato Hiroki , Tomida Shuta , Yamamoto Hiromasa , Soh Junichi , Fujiwara Toshiyoshi , Toyooka Shinichi
Published: June 2019

Cancer treatment, especially that for breast and lung cancer, has entered a new era and continues to evolve, with the development of genome analysis technology and the advent of molecular targeted drugs including tyrosine kinase inhibitors. Nevertheless, acquired drug resistance to molecular targeted drugs is unavoidable, creating a clinically challenging problem. We recently reported the antitumor effect of a pan‐HER inhibitor, afatinib, against human epidermal growth factor receptor 2 (HER2)‐amplified gastric cancer cells. The purpose of the present study was to identify the mechanisms of acquired afatinib resistance and to investigate the treatment strategies for HER2‐amplified gastric cancer cells. Two afatinib‐resistant gastric cancer cell lines were established from 2 HER2‐amplified cell lines, N87 and SNU216. Subsequently, we investigated the molecular profiles of resistant cells. The activation of the HER2 pathway was downregulated in N87‐derived resistant cells, whereas it was upregulated in SNU216‐derived resistant cells. In the N87‐derived cell line, both MET and AXL were activated, and combination treatment with afatinib and cabozantinib, a multikinase inhibitor that inhibits MET and AXL, suppressed the cell growth of cells with acquired resistance both in vitro and in vivo. In the SNU216‐derived cell line, YES1, which is a member of the Src family, was remarkably activated, and dasatinib, a Src inhibitor, exerted a strong antitumor effect in these cells. In conclusion, we identified MET and AXL activation in addition to YES1 activation as novel mechanisms of afatinib resistance in HER2‐driven gastric cancer. Our results also indicated that treatment strategies targeting individual mechanisms of resistance are key to overcoming such resistance.
Impact of number of registration points on the positional accuracy of a prosthetic treatment plan incorporated into a cone beam computed tomography scan by surface scan registration: An in vitro study
Authors: Jamjoom Faris Z. , Yilmaz Burak , Johnston William M.
Published: June 2019

Objectives

To evaluate the accuracy of a prosthetic treatment plan incorporation into a cone beam computed tomography (CBCT) scan using point‐based registration with three registration points selected and to evaluate the impact of number of registration points on prosthetic plan accuracy.

Material and Methods

A CBCT scan of a completely dentate master model with removable teeth was exposed after removing the mandibular left first premolar, second premolar, and first molar. A digital scan of the master model with all teeth present was made by scanning a stone replica using a laboratory scanner. The digital model was registered onto the three‐dimensional (3D) volume rendering of the CBCT scan using implant planning software. The point‐based registration was repeated using three, four, five, six, seven, eight, nine, and 10 reference points. Metrology software was used to measure the 3D deviation of the registered models for each reference point group on standard tessellation language (STL) files obtained from the CBCT scans. An STL file of the master model with all teeth present obtained from another CBCT scan was used as reference.

Results

Using three registration points, the registered prosthetic plan had a mean absolute deviation of 17.63 µm from the reference. Increasing the number of registration points failed to demonstrate statistically significant effects on the deviation (p > 0.05).

Conclusions

For this clinical scenario, three registration points provided adequate accuracy for prosthetic plan incorporation into CBCT scans. Increasing the number of registration points had no significant impact on the prosthetic plan accuracy in this study.
Eruptive ulcerative follicular spicules heralding progression of smoldering multiple myeloma
Authors: Tomasini Carlo , Michelerio Andrea , Brazzelli Valeria
Published: June 2019

Herein, we describe a patient with immunoglobulin G (IgG)‐lambda smoldering multiple myeloma with translocation t(4:14) who developed widespread ulcerative horny‐like spicules, heralding rapid progression to overt myeloma requiring aggressive chemotherapy and autologous stem cell transplantation. The serum abnormal immunoglobulin in the blood was cryoglobulin, which typically precipitates in the tissues at low temperatures causing inflammation and tissue damage. Histopathological changes, observed in lesions at different evolutionary stages, evidenced columns of horny‐like eosinophilic homogeneous material, immunoreactive for IgG lambda, protruding from the dilated and/or distorted follicular openings or acrosyringia and small vessel thrombotic vasculopathy and vasculitis in concert with an inflammatory neutrophilic and lymphocytic reaction. Biochemical investigations on material from a spicule and ulcero‐necrotic lesion revealed cryoprecipitates containing IgG‐lambda with electrophoretic characteristics identical to those of the serum dysprotein. Our findings suggest that the formation of spicules and development of ulcerative lesions are a part of the same clinical spectrum where the cold‐dependent precipitation of the immunogenic dysprotein, both in the skin vessels and hair follicle infundibula, play a major pathogenetic role. Whether this highly characteristic paraneoplastic dermatosis can identify patients with high‐risk cytogenetic abnormalities and be incorporated into prognostic models, applicable early on in the course of myeloma, warrants further investigation.