bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating risk of encapsulating peritoneal sclerosis accounting for the competing risk of death
Authors: Lambie Mark , Teece Lucy , Johnson David W , Petrie Michaela , Mactier Robert , Solis-Trapala Ivonne , Belcher John , Bekker Hilary L , Wilkie Martin , Tupling Ken , Phillips-Darby Louise , Davies Simon J
Published: February 2019

Background

Risk of encapsulating peritoneal sclerosis (EPS) is strongly associated with the duration of peritoneal dialysis (PD), such that patients who have been on PD for some time may consider elective transfer to haemodialysis to mitigate the risk of EPS. There is a need to determine this risk to better inform clinical decision making, but previous studies have not allowed for the competing risk of death.

Methods

This study included new adult PD patients in Australia and New Zealand (ANZ; 1990–2010) or Scotland (2000–08) followed until 2012. Age, time on PD, primary renal disease, gender, data set and diabetic status were evaluated as predictors at the start of PD, then at 3 and 5 years after starting PD using flexible parametric competing risks models.

Results

In 17 396 patients (16 162 ANZ, 1234 Scotland), EPS was observed in 99 (0.57%) patients, less frequently in ANZ patients (n = 65; 0.4%) than in Scottish patients (n = 34; 2.8%). The estimated risk of EPS was much lower when the competing risk of death was taken into account (1 Kaplan–Meier = 0.0126, cumulative incidence function = 0.0054). Strong predictors of EPS included age, primary renal disease and time on PD. The risk of EPS was reasonably discriminated at the start of PD (C-statistic = 0.74–0.79) and this improved at 3 and 5 years after starting PD (C-statistic = 0.81–0.92).

Conclusions

EPS risk estimates are lower when calculated using competing risk of death analyses. A patient’s estimated risk of EPS is country-specific and can be predicted using age, primary renal disease and duration of PD.
Hypertonic Saline is Superior to Mannitol for the Combined Effect on Intracranial Pressure and Cerebral Perfusion Pressure Burdens in Patients With Severe Traumatic Brain Injury
Authors: Mangat Halinder S , Wu Xian , Gerber Linda M , Schwarz Justin T , Fakhar Malik , Murthy Santosh B , Stieg Philip E , Ghajar Jamshid , Härtl Roger
Published: February 2019

BACKGROUND

Hypertonic saline (HTS) and mannitol are effective in reducing intracranial pressure (ICP) after severe traumatic brain injury (TBI). However, their simultaneous effect on the cerebral perfusion pressure (CPP) and ICP has not been studied rigorously.

OBJECTIVE

To determine the difference in effects of HTS and mannitol on the combined burden of high ICP and low CPP in patients with severe TBI.

METHODS

We performed a case–control study using prospectively collected data from the New York State TBI-trac® database (Brain Trauma Foundation, New York, New York). Patients who received only 1 hyperosmotic agent, either mannitol or HTS for raised ICP, were included. Patients in the 2 groups were matched (1:1 and 1:2) for factors associated with 2-wk mortality: age, Glasgow Coma Scale score, pupillary reactivity, hypotension, abnormal computed tomography scans, and craniotomy. Primary endpoint was the combined burden of ICPhigh (> 25 mm Hg) and CPPlow (< 60 mm Hg).

RESULTS

There were 25 matched pairs for 1:1 comparison and 24 HTS patients matched to 48 mannitol patients in 1:2 comparisons. Cumulative median osmolar doses in the 2 groups were similar. In patients treated with HTS compared to mannitol, total number of days (0.6 ± 0.8 vs 2.4 ± 2.3 d, P < .01), percentage of days with (8.8 ± 10.6 vs 28.1 ± 26.9%, P < .01), and the total duration of ICPhigh + CPPlow (11.12 ± 14.11 vs 30.56 ± 31.89 h, P = .01) were significantly lower. These results were replicated in the 1:2 match comparisons.

CONCLUSION

HTS bolus therapy appears to be superior to mannitol in reduction of the combined burden of intracranial hypertension and associated hypoperfusion in severe TBI patients.
Phase dependence of response curves to stimulation and their relationship: from a Wilson-Cowan model to essential tremor patient data
Authors: Duchet Benoit , Weerasinghe Gihan , Cagnan Hayriye , Brown Peter , Bick Christian , Bogacz Rafal
Published: February 2019

Essential tremor manifests predominantly as a tremor of the upper limbs. One therapy option is high-frequency deep brain stimulation, which continuously delivers electrical stimulation to the ventral intermediate nucleus of the thalamus at about 130 Hz. Investigators have been looking at stimulating less, chiefly to reduce side effects. One strategy, phase-locked deep brain stimulation, consists of stimulating according to the phase of the tremor, once per period. In this study, we aim to reproduce the phase dependent effects of stimulation seen in patient data with a biologically inspired Wilson-Cowan model. To this end, we first analyse patient data, and conclude that half of the datasets have response curves that are better described by sinusoidal curves than by straight lines, while an effect of phase cannot be consistently identified in the remaining half. Using the Hilbert phase we derive analytical expressions for phase and amplitude responses to phase-dependent stimulation and study their relationship in the linearisation of a stable focus model, a simplification of the Wilson-Cowan model in the stable focus regime. Analytical results provide a good approximation for response curves observed in patients with consistent significance. Additionally, we fitted the full non-linear Wilson-Cowan model to these patients, and we show that the model can fit in each case to the dynamics of patient tremor as well as the phase response curve, and the best fits are found to be stable foci for each patients (tied best fit in one instance). The model provides satisfactory prediction of how patient tremor will react to phase-locked stimulation by predicting patient amplitude response curves although they were not explicitly fitted. This can be partially explained by the relationship between the response curves in the model being compatible with what is found in the data. We also note that the non-linear Wilson-Cowan model is able to describe response to stimulation more precisely than the linearisation.
Label-free Method for Classification of T cell Activation
Authors: Walsh Alex J. , Mueller Katie , Jones Isabel , Walsh Christine M. , Piscopo Nicole , Niemi Natalie N. , Pagliarini David J. , Saha Krishanu , Skala Melissa C.
Published: February 2019

T cells have a range of cytotoxic and immune-modulating functions, depending on activation state and subtype. However, current methods to assess T cell function use exogenous labels that often require cell permeabilization, which is limiting for time-course studies of T cell activation and non-destructive quality control of immunotherapies. Label-free optical imaging is an attractive solution. Here, we use autofluorescence imaging of NAD(P)H and FAD, co-enzymes of metabolism, to quantify optical imaging endpoints in quiescent and activated T cells. Machine learning classification models were developed for label-free, non-destructive determination of T cell activation state. T cells were isolated from the peripheral blood of human donors, and a subset were activated with a tetrameric antibody against CD2/CD3/CD28 surface ligands. NAD(P)H and FAD autofluorescence intensity and lifetime of the T cells were imaged using a multiphoton fluorescence lifetime microscope. Significant differences in autofluorescence imaging end-points were observed between quiescent and activated T cells. Feature selection methods revealed that the contribution of the short NAD(P)H lifetime (α1) is the most important feature for classification of activation state, across multiple donors and T cell subsets. Logistic regression models achieved 97-99% accuracy for classification of T cell activation from the autofluorescence imaging endpoints. Additionally, autofluorescence imaging revealed NAD(P)H and FAD autofluorescence differences between CD3+CD8+and CD3+CD4+T cells, and random forest models of the autofluorescence imaging endpoints achieved 97+% accuracy for four-group classification of quiescent and activated CD3+CD8+and CD3+CD4+T cells. Altogether these results indicate that autofluorescence imaging of NAD(P)H and FAD is a powerful method for label-free, non-destructive determination of T cell activation and subtype, which could have important applications for the treatment of cancer, autoimmune, infectious, and other diseases.
Hypertrophic cardiomyopathy mutations at the folded-back sequestered β-cardiac myosin S1-S2 and S1-S1 interfaces release sequestered heads and increase myosin enzymatic activity
Authors: Adhikari Arjun S. , Trivedi Darshan V. , Sarkar Saswata S. , Song Dan , Kooiker Kristina B. , Bernstein Daniel , Spudich James A. , Ruppel Kathleen M.
Published: February 2019

Hypertrophic cardiomyopathy (HCM) affects 1 in 500 people and leads to hyper-contractility of the heart. Nearly 40 percent of HCM-causing mutations are found in human β-cardiac myosin. Previous studies looking at the effect of HCM mutations on the force, velocity and ATPase activity of the catalytic domain of human β-cardiac myosin have not shown clear trends leading to hypercontractility at the molecular scale. Here we present functional data showing that four separate HCM mutations located at the myosin head-tail (R249Q, H251N) and head-head (D382Y, R719W) interfaces of a folded-back sequestered state referred to as the interacting heads motif lead to a significant increase in the number of heads functionally accessible for interaction with actin. These results provide evidence that HCM mutations can modulate myosin activity by disrupting intramolecular interactions within the proposed sequestered state, thereby leading to hypercontractility at the molecular level.
Impact of population structure in the design of RNA-based diagnostics for antibiotic resistance in Neisseria gonorrhoeae
Authors: Wadsworth Crista B. , Sater Mohamad R.A. , Bhattacharyya Roby P. , Grad Yonatan H.
Published: February 2019

Quantitative assessment of antibiotic-responsive RNA transcripts holds promise for a rapid point of care (POC) diagnostic tool for antimicrobial susceptibility testing. These assays aim to distinguish susceptible and resistant isolates by transcriptional differences upon drug exposure. However, an often-overlooked dimension of designing these tests is that the genetic diversity within a species may yield differential transcriptional regulation independent of resistance phenotype. Here, we use a phylogenetically diverse panel of Neisseria gonorrhoeae and transcriptome profiling coupled with RT-qPCR to test this hypothesis, to identify azithromycin responsive transcripts and evaluate their potential diagnostic value, and to evaluate previously reported diagnostic markers for ciprofloxacin resistance (porB and rpmB). Transcriptome profiling confirmed evidence of population structure in transcriptional response to azithromycin. Taking this population structure into account, we found azithromycin-responsive transcripts overrepresented in susceptible strains compared to resistant strains, and selected four candidate diagnostic transcripts (rpsO, rplN, omp3, and NGO1079) that were the most significantly differentially regulated between phenotypes across drug exposure. RNA signatures for these markers categorically predicted resistance in 19/20 cases, with the one incorrect categorical assignment for an isolate at the threshold of reduced susceptibility. Finally, we found that porB and rpmB expression were not diagnostic of ciprofloxacin resistance in a panel of isolates with unbiased phylogenetic sampling. Overall, our results suggest that RNA signatures as a diagnostic tool are promising for future POC diagnostics; however, development and testing should consider representative genetic diversity of the target pathogen.
Fetal stage melanopsin (OPN4) and GNAQ (Gαq) signaling regulates vascular development of the eye
Authors: Vemaraju Shruti , Nayak Gowri , Miller William E. , Copenhagen David R. , Lang Richard A.
Published: February 2019

Maturation of sensory systems in mammals is regulated by appropriate sensory stimulation. Developmental refinement of the eye and visual system is regulated by light and visual stimulation. One compelling example is that fetal mouse pups deprived of light exhibit altered vascular development in their eyes. Previous work demonstrated that light activation of the photopigment melanopsin (Opn4), an atypical opsin expressed in intrinsically photosensitive retinal ganglion cells (ipRGCs), is crucial to normal vascular development. This suggested the unusual hypothesis that vascular development of the eye was regulated by ipRGC responses in the fetal eye by light that traveled through the body wall of the mother. Here, we test the requirement of OPN4 during fetal stages using genetic approaches. The G-protein GNAQ (Gαq) is a candidate mediator of melanopsin signaling. We show that ipRGC-specific deletion of Gnaq phenocopies both hyaloid and retinal vascular development of the Opn4 null mouse. Furthermore, GNAQ gain-of-function in Opn4-expressing cells only during late gestation was sufficient to reverse the consequences for vascular development of either dark rearing or Opn4 loss-of-function. We conclude that melanopsin-dependent signaling in the fetal mouse eye is necessary and sufficient for vascular maturation.
Increasing molar activity by HPLC purification improves 68Ga-DOTA-NAPamide tumor accumulation in a B16/F1 melanoma xenograft model
Authors: Hacht Jan Lennart von , Erdmann Sarah , Niederstadt Lars , Prasad Sonal , Wagener Asja , Exner Samantha , Beindorff Nicola , Brenner Winfried , Grötzinger Carsten
Published: February 2019

Purpose

Melanocortin receptor 1 is overexpressed in melanoma and may be a molecular target for imaging and peptide receptor radionuclide therapy. 68Gallium labeling of DOTA-conjugated peptides is an established procedure in the clinic for use in positron emission tomography imaging. Aim of this study was to compare a standard labeling protocol against the 68Ga-DOTA peptide purified from the excess of unlabeled peptide.

Procedures

The MC1R ligand DOTA-NAPamide was labeled with 68Ga using a standard clinical protocol. Radioactive peptide was separated from the excess of unlabeled DOTA-NAPamide by HPLC. Immediately after the incubation of peptide and 68Ga (95 °C, 15 min), the reaction was loaded on a C18 column and separated by a water/acetonitrile gradient, allowing fractionation in less than 20 minutes. Radiolabeled products were compared in biodistribution studies and PET imaging using nude mice bearing MC1R-expressing B16/F1 xenograft tumors.

Results

In biodistribution studies, the non-purified 68Ga-DOTA-NAPamide did not show significant uptake in the tumor at 1 h post injection (0.78% IA/g). By the additional HPLC step, the molar activity was raised around 10,000-fold by completely removing unlabeled peptide. Application of this rapid purification strategy led to a more than 8-fold increase in tumor uptake (7.0% IA/g). The addition of various amounts of unlabeled DOTA-NAPamide to the purified product led to a blocking effect and a decreased specific tumor uptake, similar to the result seen with non-purified radiopeptide. PET imaging was performed using the same tracers for biodistribution. Purified 68Ga-DOTA-NAPamide, in comparison, showed superior tumor uptake.

Conclusions

We demonstrated that chromatographic separation of radiolabeled from excess unlabeled peptide is technically feasible and beneficial, even for short-lived isotopes such as 68Ga. Unlabeled peptide molecules compete with receptor binding sites in the target tissue. Purification of the radiopeptide therefore improved tumor uptake.
Conformational and dynamical plasticity in substrate-binding proteins underlies selective transport in ABC importers
Authors: de Boer Marijn , Gouridis Giorgos , Vietrov Ruslan , Begg Stephanie L. , Schuurman-Wolters Gea K. , Husada Florence , Eleftheriadis Nikolaos , Poolman Bert , McDevitt Christopher A. , Cordes Thorben
Published: February 2019

Substrate-binding proteins (SBPs) are associated with ATP-binding cassette importers and switch from an open-to a closed-conformation upon substrate binding providing specificity for transport. We investigated the effect of substrates on the conformational dynamics of six SBPs and the impact on transport. Using single-molecule FRET, we reveal an unrecognized diversity of plasticity in SBPs. We show that a unique closed SBP conformation does not exist for transported substrates. Instead, SBPs sample a range of conformations that activate transport. Certain non-transported ligands leave the structure largely unaltered or trigger a conformation distinct from that of transported substrates. Intriguingly, in some cases similar SBP conformations are formed by both transported and non-transported ligands. In this case, the inability for transport arises from slow opening of the SBP or the selectivity provided by the translocator. Our results reveal the complex interplay between ligand-SBP interactions, SBP conformational dynamics and substrate transport.
Conservation of N-hydroxy-pipecolic acid-mediated systemic acquired resistance in crop plants
Authors: Holmes Eric C. , Chen Yun-Chu , Sattely Elizabeth , Mudgett Mary Beth
Published: February 2019

Signal propagation and the coordination of whole-organism responses in plants rely heavily on small molecules. Systemic acquired resistance (SAR) is one such process in which long-distance signaling activates immune responses in uninfected tissue as a way to limit the spread of a primary, localized infection. Recently, N-hydroxy pipecolic acid (NHP) was discovered and shown to coordinate SAR in Arabidopsis. Here, we provide metabolic and biochemical evidence that NHP is conserved across the plant kingdom and demonstrate a role for NHP in mediating SAR responses in tomato and pepper. We reconstituted the NHP biosynthetic pathway in planta and show that transient expression of two NHP biosynthetic genes in tomato induces enhanced resistance to a bacterial pathogen in distal tissue. Our results suggest engineering strategies to induce NHP-mediated SAR are a promising route to improve broad-spectrum pathogen resistance in crops.

IN BRIEF

Engineering NHP production is a promising strategy to enhance disease resistance in crops.

HIGHLIGHTS

Arabidopsis N-hydroxy-pipecolic acid (NHP) pathway is conserved across the plant kingdom

Application of NHP to tomato and pepper plants induces a robust SAR response

Metabolic engineering of the Arabidopsis NHP pathway in Solanum lycopersicum leads to enhanced NHP production and defense priming

Genetic engineering for enhanced NHP production is a promising strategy to protect crop plants from multiple pathogens
A real-time PCR for the differentiation of typhoidal and non-typhoidal Salmonella
Authors: Nair Satheesh , Patel Vineet , Hickey Tadgh , Maguire Clare , Greig David R , Lee Winnie , Godbole Gauri , Grant Kathie , Chattaway Marie Anne
Published: February 2019

Rapid and accurate differentiation of Salmonella spp. causing enteric fever from non-typhoidal Salmonella is essential for clinical management of cases, laboratory risk management and implementation of public health measures. Current methods used for confirmation of identification including biochemistry and serotyping as well as whole genome sequencing analyses, takes several days. Here we report the development and evaluation of a real-time PCR assay that can be performed directly on crude DNA extracts from bacterial colonies, for the rapid identification of typhoidal and non-typhoidal Salmonella.

This novel two-hour assay identifies the genus Salmonella by detecting the ttr gene, encoding tetrathionate reductase, and defines typhoidal Salmonella by the detection of S. Typhi and Paratyphi-specific gene combinations. PCR assay performance was determined using 211 clinical cultures of Salmonella (114 non-typhoidal and 97 Typhoidal strains) and 7 clinical non-Salmonella cultures. In addition, the specificity of the assay was evaluated in silico using a diverse in-house collection of 1882 Salmonella whole genome sequences. The real-time PCR results for 218 isolates and the genomic analysis of the 1882 isolates produced 100% sensitivity and 100% specificity (based on a 7 gene profile) for identifying typhoidal Salmonella compared to the Salmonella whole genome sequening identification methods currently used at Public Health England.

This paper describes a robust real-time PCR assay for the rapid, accurate identification of typhoidal and non-typhoidal Salmonella which will be invaluable for the urgent screening of isolates from symptomatic individuals, the safe processing of isolates in laboratories and for assisting the management of public health risks.
Peripheral axonal ensheathment is regulated by Ral GTPase and the exocyst complex
Authors: Silva-Rodrigues Joana F. , Patrício-Rodrigues Cátia F. , Sousa-Xavier Vicente de , Augusto Pedro M. , Fernandes Ana C. , Farinho Ana R. , Teodoro Rita O.
Published: February 2019

Axon ensheathment is fundamental for fast impulse conduction and the normal physiological functioning of the nervous system. Defects in axonal insulation lead to debilitating conditions, but despite its importance, the molecular players responsible are poorly defined. Here, we identify Ral GTPase as a key player in axon ensheathment inDrosophilalarval peripheral nerves. We demonstrate through genetic analysis that Ral action through the exocyst complex is sufficient and necessary in wrapping glial cells to regulate their growth and development. We suggest that the Ral-exocyst pathway controls the targeting of secretory vesicles for membrane growth or for the secretion of a wrapping glia-specific factor that itself regulates growth. In summary, our findings provide a new molecular understanding of the process by which axons are ensheathedin vivo, a process critical for normal neuronal function.
Nested Polymerase Chain Reaction (PCR)
Authors: Green Michael R. , Sambrook Joseph
Published: February 2019

Nested polymerase chain reaction (PCR) is used in situations in which it is necessary to increase the sensitivity and/or specificity of PCR, for example, when amplifying a particular member of a polymorphic gene family or when amplifying a cDNA copy of an mRNA present at very low abundance in a clinical specimen containing a heterogeneous population of cell types. Nested PCR usually involves two sequential amplification reactions, each of which uses a different pair of primers. The product of the first amplification reaction is used as the template for the second PCR, which is primed by oligonucleotides that are placed internal to the first primer pair. The use of two pairs of oligonucleotides allows a higher number of cycles to be performed, thereby increasing the sensitivity of the PCR. The improved specificity of the reaction derives from the binding of two separate sets of primers to the same target template. Nested PCR is an efficient method to amplify segments of long templates but requires knowledge of the sequence of the target.
Plant host identity and soil macronutrients explain little variation in sapling endophyte community composition: Is disturbance an alternative explanation?
Authors: Griffin Eric A. , Harrison Joshua G. , Kembel Steven W. , Carrell Alyssa A. , Joseph Wright S. , Carson Walter P.
Published: February 2019

Bacterial endophytes may be fairly host‐specific; nonetheless, an important subset of taxa may be shared among numerous host species forming a community‐wide core microbiome. Moreover, other key factors, particularly the supply of limiting macronutrients and disturbances, may supersede the importance of host identity.

We tested the following four non‐mutually exclusive hypotheses: (a)The Host Identity Hypothesis: endophytes vary substantially among different host‐plant species. (b)The Core Microbiome Hypothesis: a subset of microbial taxa will be shared among all host‐plant species. (c).The Soil Resource Supply Hypothesis: endophytes vary substantially among habitats with experimentally elevated levels of macronutrients. (d)The Disturbance–Disruption Hypothesis: disturbances created by the periodic application of antibiotics structure bacterial endophyte communities.

We tested these hypotheses by characterizing endophytes using high‐throughput sequencing among seedlings of five phylogenetically diverse tree species nested within a long‐term, full factorial nitrogen, phosphorus and potassium soil fertilization experiment. We artificially disturbed one of our focal species by applying antibiotics every 10–14 days for 29 months within the soil (N, P, K) fertilization experiment.

While we detected a significant effect of host identity and soil nutrient additions,togetherthey explained little variation in endophyte community composition (<10%). We found unequivocal evidence for a core microbiome shared by all species. Specifically, we inferred that nine OTUs were present among 95% or more of all control saplings, representing a third of the total reads. These bacterial taxa belonged to the Actinobacteria.

In contrast, disturbance (antibiotics) explained more endophyte variation than all nutrient addition combinationscombinedand twice the variation explained by host identity for all five tree species.

Synthesis. Our results challenge the idea that host identity is a primary filter shaping bacterial endophyte communities; this suggests that many of the same bacterial taxa occur inside plant hosts even if those host plants are phylogenetically diverse. Moreover, we documented a distinct core microbiome shared among our five focal tree species. Finally, we found that disturbance rather than host identity and soil nutrient availability was an important driver of microbial community composition, which parallels the importance of disturbance in other areas of community ecology.
Identification of three podoviruses infecting Klebsiella encoding capsule depolymerases that digest specific capsular types
Authors: Pan Yi‐Jiun , Lin Tzu‐Lung , Chen Yi‐Yin , Lai Peng‐Hsuan , Tsai Yun‐Ting , Hsu Chun‐Ru , Hsieh Pei‐Fang , Lin Yi‐Tsung , Wang Jin‐Town
Published: February 2019

Klebsiella pneumoniae is an important human pathogen causing opportunistic nosocomial and community‐acquired infections. A major public health concern regarding K. pneumoniae is the increasing incidence of multidrug‐resistant strains. Here, we isolated three novel Klebsiella bacteriophages, KN1‐1, KN3‐1 and KN4‐1, which infect KN1, KN3 and K56, and KN4 types respectively. We determined their genome sequences and conducted a comparative analysis that revealed a variable region containing capsule depolymerase‐encoding genes. Recombinant depolymerase proteins were produced, and their enzymatic activity and specificity were evaluated. We identified four capsule depolymerases in these phages that could only digest the capsule types of their respective hosts. Our results demonstrate that the activities of these capsule depolymerases were correlated with the host range of each phage; thus, the capsule depolymerases are host specificity determinants. By generating a capsule mutant, we demonstrate that capsule was essential for phage adsorption and infection. Further, capsule depolymerases can enhance bacterial susceptibility to serum killing. The discovery of these phages and depolymerases lays the foundation for the typing of KN1, KN3, KN4 and K56 Klebsiella and could be useful alternative therapeutics for the treatment of K. pneumoniae infections.
Scholarly Productivity and Impact: Developing a Quantifiable, Norm‐based Benchmarking Methodology for Academic Emergency Medicine
Authors: Boudreaux Edwin D. , Higgins Stephen E. , Reznik‐Zellen Rebecca , Wang Bo , Volturo Gregory
Published: February 2019

Background

Quantifying and benchmarking scholarly productivity of emergency medicine faculty is challenging. While performance indicators including publication and citation counts are available, use of indicators to create normative references has lagged. The authors developed methodology to benchmark emergency medicine academician scholarly productivity (e.g., publications over time) and impact (e.g., citations per publication over time) against an appropriate reference group.

Methods

The methodology includes: 1) define time frame and scholarly metrics; 2) identify representative population; 3) reconcile alternative author names; 4) use analytic tool to identify scholarly output; 5) build database containing metrics; and 6) create benchmarking statistics, including subsamples. This study included emergency medicine faculty from 2011 to 2015, with total peer‐reviewed publications and citations per publication as scholarly metrics.

Results

In the United States at the time of the search (2016) there were 200 academic emergency departments, 186 with public faculty listings, which yielded 6,727 academicians. For each academician, the authors calculated statistics about peer‐reviewed publications and average citations per publication from 2011 to 2015 and created benchmarking rulers using percentile ranks. Productivity by year of graduation with terminal degree was compared within each subsample, finding that newly graduated faculty demonstrated higher productivity than their within‐rank peers who graduated earlier. Finally, benchmarking tables were created that allow comparison of peer‐reviewed publication counts and citations per publication for individual academicians against the norm.

Conclusions

This benchmarking method can serve as a model for norm‐based scaling of scholarly productivity for emergency medicine. This has important implications for performance review, promotion and hiring, and evaluating group productivity.
Forecasting wildlife die‐offs from extreme heat events
Authors: Ratnayake H. U. , Kearney M. R. , Govekar P. , Karoly D. , Welbergen J. A.
Published: February 2019

Extreme heat events pose increasing challenges to biodiversity conservation worldwide, yet our ability to predict the time, place and magnitude of their impacts on wildlife is limited. Extreme heat events in Australia are known to kill thousands of flying‐foxes (Pteropus spp.), and such die‐offs are expected to become more frequent and widespread in the future under anthropogenic climate change. There is a growing need for predicting when and where such heat‐related die‐offs would occur, to facilitate short‐term wildlife management and conservation actions. In this study, we used gridded hourly air temperature forecasts [Australian Community Climate and Earth‐System Simulator (ACCESS‐R) Numerical Weather Prediction (NWP) model] from the Australian Bureau of Meteorology to predict flying‐fox heat‐related mortality based on an empirically determined threshold of 42.0°C. We tested the accuracy and precision of this model using a twofold evaluation of the ACCESS‐R NWP forecast air temperature during a recorded extreme heat event with in situ air temperature measurements and interpolated weather station data. While our results showed a slight discrepancy between the modelled and measured air temperatures, there was no significant difference in the forecast's accuracy to predict die‐offs during an extreme heat event and the overall summer period. We evaluated the accuracy of mortality predictions based on different air temperature thresholds (38.0, 40.0, 42.0 and 44.0°C). Our results revealed a significant probability of flying‐fox mortality occurrence when forecast air temperature was ≥42.0°C, while the 24‐ and 48‐h forecasts accurately predicted 77 and 73% of the die‐offs, respectively. Thus, the use of 42.0°C forecast air temperature from the ACCESS‐R NWP model can predict flying‐fox mortality reliably at the landscape scale. In principle, the forecaster can be used for any species with known thermal tolerance data and is therefore a promising new tool for prioritizing adaptation actions that aim to conserve biodiversity in the face of climate change.
Control of the banded fruit weevil Phlyctinus callosus (Coleoptera: Curculionidae) using entomopathogenic nematodes
Authors: Dlamini Bonginkhosi E , Malan Antoinette P , Addison Pia
Published: February 2019

Phlyctinus callosus (Schönherr), the banded fruit weevil, is a key pest of deciduous fruit and grapevine in the Western Cape province of South Africa. Entomopathogenic nematodes (EPNs), as a biocontrol agent, are found to be effective in controlling both soilborne and above‐ground insect pests. Different EPN species were screened for virulence against different life stages of P. callosus, followed by a field trial, in which Steinernema yirgalemense was applied at different concentrations. S. yirgalemense, Heterorhabditis noenieputensis and the exotic Steinernema feltiae gave good control of P. callosus larvae at 100 infective juveniles per insect, with no significant difference between treatments. In the case of P. callosus pupae, Heterorhabditis indica (70%) and Heterorhabditis baujardi (67%) differed significantly (P < 0.05) in their control, compared with H. noenieputensis (55%). H. indica (95%) and S. yirgalemense (94%) gave significantly higher (P < 0.05) control of P. callosus adults, compared with the three other nematode species tested. In the field trials, S. yirgalemense, at 20 and 40 infective juveniles/cm2, gave 69% and 78% control of P. callosus larvae after 48 h of exposure, respectively. The results indicated that all EPNs tested were effective against the immature and adult stages of P. callosus, with differences in mortality among the EPN species tested. S. yirgalemense, at low concentration, can effectively control P. callosus under field conditions, but large‐scale field trials are recommended to demonstrate the potential use of this biocontrol agent within integrated pest management programmes.
Surveillance colonoscopies frequently booked earlier than the National Health and Medical Research Council guidelines: findings of a single centre audit
Authors: Bunjo Zachary , Koh Yu Han , Leopardi Lisa , Reid Jessica , Maddern Guy J. , Hewett Peter J.
Published: February 2019

Background

To assess the adherence rate of surveillance colonoscopy booking intervals to recommended National Health and Medical Research Council guidelines at The Queen Elizabeth Hospital, Adelaide, Australia.

Methods

Patients on The Queen Elizabeth Hospital colorectal unit surveillance colonoscopy waiting list were included in this audit. Patient demographics, colonoscopy findings, follow‐up plans and pathology results were analysed. Patients were categorized as normal/non‐neoplastic finding, low‐risk adenomas, high‐risk adenomas, personal history of colorectal cancer (CRC) and family history of CRC. Booked colonoscopy within 2 months of guideline recommended interval was considered correct.

Results

A total of 467 patients were included (59.1% male; mean age 60 years). Two hundred and fifty‐one (53.7%) patients had an incorrect surveillance colonoscopy booking. Twenty‐seven patients with a normal/non‐neoplastic previous colonoscopy not requiring surveillance colonoscopy were incorrectly booked for a colonoscopy. For the 222 patients booked incorrectly and requiring surveillance colonoscopy, 88.7% were early and 11.3% were late. The proportions of incorrect bookings were highest in the low‐risk finding (66.1%) and history of CRC (67.6%) groups. For the 186 patients requiring a 3‐year surveillance interval, 38.7% were booked incorrectly. For the 197 patients requiring a 5‐year surveillance interval, 63.5% were booked incorrectly, of which 99.2% were early. More 5‐year surveillance interval patients were booked at 3 years (n = 79), than at the correct interval of 5 years (n = 72).

Conclusion

Adherence to the National Health and Medical Research Council guidelines for surveillance colonoscopy is poor. The majority of deviations represent early follow‐up, which is most common among patients with low‐risk findings or history of CRC. There is a tendency towards 3‐year surveillance among low‐risk patients.
Systematic review with meta‐analysis: cholecystectomy for biliary dyskinesia—what can the gallbladder ejection fraction tell us?
Authors: Gudsoorkar Vineet S. , Oglat Ayah , Jain Amita , Raza Ali , Quigley Eamonn M. M.
Published: February 2019

Background

Gallbladder dyskinesia (gallbladder spasm, biliary dyskinesia or chronic acalculous cholecystitis) is a poorly defined entity which presents as biliary‐type pain without any identifiable organic pathology. Abnormal gallbladder ejection fraction (GBEF) is used by some to select those likely to benefit from cholecystectomy. The validity of this approach has been questioned.

Aim

To systematically review the literature and summarise the evidence surrounding the practice of cholecystectomy based on GBEF for gallbladder dyskinesia.

Methods

We conducted a systematic search of PubMed/MEDLINE and SCOPUS from 1980 to 2016 to identify the relevant literature.

Results

Twenty‐nine studies including 2891 patients were included in the final analysis. In comparing cholecystectomy with medical management, patients with a normal GBEF did not benefit from cholecystectomy; whereas those with low GBEF had a higher chance (RR, relative risk = 2.37) of symptomatic improvement following surgery. When those classified as “low” and “normal” GBEF were compared in terms of outcome following cholecystectomy, the rate of improvement following surgery was similar in the two groups (RR 1.09) which suggests a placebo effect of surgery.

Conclusions

While a low GBEF may provide some guidance in identifying those with gallbladder dyskinesia who may benefit from cholecystectomy, the available data are inconsistent and based on studies of poor quality which are often subject to bias and the impact of confounding factors. For these reasons, we conclude that the role of scintigraphy and cholecystectomy in the definition and management of this disorder remain unclear pending definitive study.
Dirty jobs and dehumanization of workers
Authors: Valtorta Roberta Rosa , Baldissarri Cristina , Andrighetto Luca , Volpato Chiara
Published: February 2019

The present study aims at expanding research on dehumanization in the work domain by exploring laypeople's dehumanizing perceptions towards stigmatized workers. Starting from Hughes’ (1951, Social psychology at the crossroads, Harper & Brothers, New York; Ashforth & Kreiner, 1999, Academy of Management Review, 24, 413) concept of ‘dirty work’, the present research aims to demonstrate that the different types of occupational taint elicit distinct dehumanizing images of certain occupational groups. Employing a cluster analysis, the results showed that workers in the physical taint cluster were most strongly associated with biological metaphors, workers in the social taint cluster were perceived as most similar to objects, and workers in the moral taint cluster were perceived as most similar to animals. The theoretical and practical implications are considered.
Blockage of SLC31A1‐dependent copper absorption increases pancreatic cancer cell autophagy to resist cell death
Authors: Yu Ze , Zhou Rongtao , Zhao Yicheng , Pan Yi , Liang Hao , Zhang Jin‐San , Tai Sheng , Jin Liang , Teng Chun‐Bo
Published: February 2019

Objectives

Clinical observations have demonstrated that copper levels elevate in several cancer types, and copper deprivation is shown to inhibit tumour angiogenesis and growth in both animal models and preclinical trials. However, the content of copper in pancreatic duct adenocarcinoma (PDAC) and whether it is a potential therapy target is still unknown.

Materials and Methods

The levels of copper in PDAC specimens were detected by ICP‐MS assays. Copper depletion in Panc‐1 or MiaPaCa‐2 cells was conducted via copper transporter 1 (SLC31A1) interference and copper chelator tetrathiomolybdate (TM) treatment. The effects of copper deprivation on cancer cells were evaluated by cell proliferation, migration, invasion, colony formation and cell apoptosis. The mechanism of copper deprivation‐caused cancer cell quiescence was resolved through mitochondrial dysfunction tests and autophagy studies. The tumour‐suppression experiments under the condition of copper block and/or autophagy inhibition were performed both in vitro and in xenografted mice.

Results

SLC31A1‐dependent copper levels are correlated with the malignant degree of pancreatic cancer. Blocking copper absorption could inhibit pancreatic cancer progression but did not increase cell death. We found that copper deprivation increased mitochondrial ROS level and decreased ATP level, which rendered cancer cells in a dormant state. Strikingly, copper deprivation caused an increase in autophagy to resist death of pancreatic cancer cells. Simultaneous treatment with TM and autophagy inhibitor CQ increased cell death of cancer cells in vitro and retarded cancer growth in vivo.

Conclusions

These findings reveal that copper deprivation‐caused cell dormancy and the increase in autophagy is a reason for the poor clinical outcome obtained from copper depletion therapies for cancers. Therefore, the combination of autophagy inhibition and copper depletion is potentially a novel strategy for the treatment of pancreatic cancer and other copper‐dependent malignant tumours.
Interannual variation of the diet shifts and their effects on the fatness and growth of age‐0 Pacific bluefin tuna (Thunnus orientalis) off the southwestern Pacific coast of Japan
Authors: Hiraoka Yuko , Fujioka Ko , Fukuda Hiromu , Watai Mikio , Ohshimo Seiji
Published: February 2019

We investigated the effect of feeding habits on the fatness (length–weight relationship (LW)) and otolith growth of age‐0 Pacific bluefin tuna (PBF) (fork length (FL) of 15.0–29.9 cm) collected off the southwestern Pacific coast of Japan from July to August during 2010–2015. The feeding rate on Clupeiformes (FRc) was substantially influenced by the path of the Kuroshio Current during early summer. We suggest that the following patterns occurred in the feeding habits of PBF. In 2012 and 2014, the short distance from the coast to the Kuroshio provided high overlap between PBF and Clupeiformes and increased the opportunity for feeding, and this pattern likely caused the observed diet shift from Crustacea to Clupeiformes by smaller PBF in the studied years than those in other years. In 2011 and 2015, the encounter probability for Clupeiformes might have been low due to the long distance to the Kuroshio Current, which led PBF to actively consume non‐Clupeiformes Teleostei. In contrast, in August 2010 and 2015, PBF did not encounter Clupeiformes or other Teleostei and may have been forced to feed on a large number of Crustacea; this effect was likely due to high water temperatures. Despite the interannual fluctuation in the timing of the diet shift and the feeding intensity (FI), these factors did not contribute to growth in length; rather, they contributed to fatness. Considering size‐dependent mortality in the larval stage, these results suggest that only fast‐growing individuals survive, even if the feeding conditions drastically change.
Resilience and affect balance of empty‐nest older adults with mild cognitive impairment in poor rural areas of Hunan province, China
Authors: Xie LiQin , Zhou Jun , Deng YunLong , Richmond Christopher J , Na Jiang
Published: February 2019

Aim

To evaluate the prevalence of mild cognitive impairment (MCI) within the empty‐nest older adults population in poor rural areas of the Hunan province of China, and to explore the effects of resilience and affective balance on cognitive functioning within this specific population.

Methods

A cross‐sectional, multistage, random cluster survey was administered to participants from March 2013 to December 2014 in the Hunan province. There were a total of 1164 participants. These participants were empty‐nest older adults who were residing in poor rural areas of the Hunan province. The data was collected in two stages. In stage 1, the participants were administered the Montreal Cognitive Assessment for screening cognitive impairment. In stage 2, the participants were screened for any potential cognitive impairment, were administered a series of neuropsychological tests and received a definitive diagnosis for MCI, if the criteria were met. Resilience and affect balance were assessed by the Chinese modified version of the Stress Resilience Quotient and the Affect Balance Scale.

Results

The prevalence of MCI was 38.40% within this empty‐nest older adult population. Significant differences were found between MCI and non‐MCI empty‐nest older adults specific to resilience and affect balance. Path analysis showed that resilience mediated the relationship between MCI and affect balance.

Conclusions

Resilience and affect balance were less prominent within the MCI empty‐nest older adults than those in the non‐MCI group. The results suggest that resilience is a mediating variable between MCI and affect balance. Geriatr Gerontol Int 2019; 19: 222–227.
Pharmacist educational interventions for cancer pain manaaement: a systematic review and meta-analvsis
Authors: Edwards Zoe , Ziegler Lucy , Craigs Cheryl , Blenkinsopp Alison , Bennett Michael I
Published: February 2019

Objectives

Educational interventions by pharmacists for patients with cancer pain aim to improve pain management, but little is known about the different components of interventions and their effectiveness. Our aim was to assess the benefit of pharmacist delivered educational interventions for patients with cancer pain. A systematic review and meta-analysis of experimental trials testing pharmacist delivered educational interventions for cancer pain was carried out to identify the components of interventions and effectiveness at improving pain-related outcomes for patients with cancer. A literature review was conducted in EMBASE, MEDLINE, CINAHL, PsycINFO, ASSIA, Web of Science and CENTRAL from inception until January 2018 searching for educational interventions involving a pharmacist for patients with cancer pain. Four studies were included involving 944 patients. Meta-analysis was carried out where possible.

Key findings

Meta-analysis of three of the four studies found that mean pain intensity in the intervention group was reduced by 0.76 on a 0–10 scale (95% confidence interval), although only two of the studies used validated measures of pain. Improvements in knowledge, side effects and patient satisfaction were seen although with less reliable measures.

Pharmacist educational interventions for patients with cancer pain have been found to show promise in reducing pain intensity. Studies were few and of varying quality. Further, good quality studies should be carried out in this area and these should be comprehensively reported. Trials measuring patient self-efficacy and patient satisfaction are needed before the impact of the pharmacist delivered interventions on these outcomes can be established.
Insight into the structures, melting points, and mechanical properties of NbSi2 from first‐principles calculations
Authors: Wang Shuang‐Lun , Pan Yong
Published: February 2019

Studies are carried out on the equilibrium structural, mechanical properties, and melting points of NbSi2 with four ground‐state crystal structures (C40, C11b, C54, and C49) using first‐principles approach. By means of the calculated formation enthalpies and phonon dispersion, it is found that these NbSi2 phases are thermodynamically and dynamically stable. C54‐NbSi2 is uncovered to possess the lowest energy and formation enthalpy, implying that it is expected to be the most favorite structure for NbSi2. The results of the calculated elastic constants reveal that four NbSi2 phases are mechanically stable. We further find that the mechanical properties of C54‐NbSi2 are superior to those of the other NbSi2 phases. The melting points of these NbSi2 phases are calculated to examine their thermal stability. The elastic anisotropy is calculated and discussed using three patterns. The results prove that C54‐ and C40‐NbSi2 have good elastic isotropy, as confirmed by the given three‐dimensional plots of elastic moduli. Analyzing the difference charge density and Mulliken overlap population provides the explanation about the relationship between bonding characteristics and mechanical properties.