bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of stimulus rate on ABR morphology and its relationship to P1 CAEP responses and auditory speech perception outcomes in children with auditory neuropathy spectrum disorder
Authors: McKnight Rosemary J. , Glick Hannah , Cardon Garrett , Sharma Anu
Published: December 2017

Objective:

Auditory neuropathy spectrum disorder (ANSD) affects approximately 5–15% of children with sensorineural hearing loss (SNHL). ANSD is characterized by the presence of otoacoustic emissions (OAE) and an absent or abnormal auditory brainstem response (ABR). The purpose of this study was to investigate the prognostic value of slow-rate ABR in predicting the auditory cortical development and auditory speech perception outcomes in case studies of children with ANSD.

Design:

ABR waveform characteristics were collected at slow stimulation rates (5.1 clicks/second) and a fast stimulation rates (>11–31.1 clicks/second, rates typically used in a clinical setting) in three case reports of children with ANSD. P1 CAEP responses and measures of auditory speech perception using the Infant Toddler Meaningful Auditory Integration Scale (IT-MAIS) were also collected in these children. Retrospective analysis was performed to evaluate the prognostic value of slow- versus fast-rate ABR in predicting P1 CAEP responses and auditory speech perception outcomes in these children.

Study sample:

Participants included case reports of three paediatric participants with a clinical diagnosis of ANSD.

Results:

Slow-rate ABR did not elicit significant improvements in waveform morphology compared to fast-rate ABR. P1 CAEP results were present in 2 out of 3 cases and were consistent with auditory speech perception outcomes.

Conclusions:

Even when ABR stimulation rates were slowed, ABR responses in these children with ANSD did not display any characteristic or replicable pattern, and ABR responses were not predictive of cortical auditory maturation or behavioural performance. In contrast, P1 CAEP responses provided valuable information regarding the maturational status of the auditory cortex and P1 CAEP responses were consistent with behavioural measures of auditory speech perception. Overall, results highlight the high prognostic value of P1 CAEP testing when used in conjunction with behavioural measures of auditory speech perception in children with ANSD.
Efficacy and Safety of Procalcitonin Guidance in Patients With Suspected or Confirmed Sepsis: A Systematic Review and Meta-Analysis*
Authors: Iankova Irena , Thompson-Leduc Philippe , Kirson Noam Y. , Rice Bernie , Hey Juliane , Krause Alexander , Schonfeld Sophie A. , DeBrase Christopher R. , Bozzette Samuel , Schuetz Philipp
Published: December 2017

Objective:

Sepsis is a leading cause of mortality in noncoronary ICUs. Although immediate start of antibiotics reduces sepsis-related mortality, antibiotics are often administered for too long, leading to suboptimal treatment and, importantly, contributes to antimicrobial resistance. Prior literature suggests that procalcitonin correlates with infection and thus may help to guide the decision on when to stop antibiotic treatment. This study was conducted as part of a regulatory submission to the U.S. Food and Drug Administration and aimed to summarize the evidence of procalcitonin guidance on efficacy and safety outcomes in adult patients with sepsis.

Data Sources:

PubMed and the Cochrane Database of Systematic Reviews.

Study Selection:

English-language randomized controlled trials evaluating procalcitonin use among adult patients with suspected or confirmed sepsis published between January 2004 and May 2016.

Data Extraction:

Inverse-variance weighting fixed and random effects meta-analyses were performed on the following efficacy and safety endpoints: antibiotic duration, all-cause mortality, and length of ICU stay. Two reviewers independently extracted data elements from identified studies and measured risk of bias with the Cochrane Risk of Bias Tool.

Data Synthesis:

From a total of 369 potentially eligible articles, 10 randomized controlled trials containing 3,489 patients were used for analysis. Procalcitonin-guided patients had shorter antibiotics duration compared with controls (7.35 vs. 8.85 d; weighted mean difference, –1.49 d; 95% CI, –2.27 to –0.71; p < 0.001). Procalcitonin use had no adverse impact on mortality (risk ratio, 0.90; 95% CI, 0.79–1.03; p = 0.114) and length of ICU stay (11.09 d vs. 11.91 d; weighted mean difference, –0.84 d; 95% CI, –2.52 to 0.84; p = 0.329).

Conclusions:

In adult patients with suspected or confirmed sepsis, procalcitonin guidance reduces antibiotics duration with no observed adverse effects on patient outcomes.
Treatment Patterns Among Women Diagnosed With Stage I-III Triple-negative Breast Cancer
Authors: Sineshaw Helmneh M. , Freedman Rachel A. , DeSantis Carol E. , Jemal Ahmedin
Published: December 2017

Objective:

To examine contemporary treatment patterns for women diagnosed with stage I-III triple-negative breast cancer (TNBC) in the United States.

Methods:

We identified 48,961 patients diagnosed with stage I-III TNBC from 2010 to 2013 in the National Cancer Data Base and created 3 treatment subcohorts (definitive locoregional therapy [appropriate local therapy, including surgery/radiation], adjuvant chemotherapy [stage II-III disease or stage I tumors with tumor size ≥1 cm], and adjuvant chemotherapy for small tumors [stage I tumors with tumor size <1 cm and node negative]). We performed descriptive analyses, calculated percentages for treatment receipt, and used multivariable modified Poisson regression models to estimate risk ratios (RRs) with 95% confidence intervals (CIs) predicting receipt of treatments.

Results:

Older age, larger tumor size, positive nodal status, and Southern/Pacific US regions, but not race/ethnicity, were strongly associated with a lower probability of receiving definitive locoregional therapy. Older age was also strongly associated with lower likelihood of adjuvant chemotherapy receipt, as were grade, negative nodal status, and higher comorbidity. For example, compared with women aged 18 to 39 years, those aged 75 to 90 years were 17% less likely to receive definitive locoregional therapy (RR, 0.83; 95% CI, 0.73-0.88), and 62% less likely to receive adjuvant chemotherapy (RR, 0.38; 95% CI, 0.35-0.41). Age, tumor grade, tumor size, and comorbidity score were also independently associated with receipt of chemotherapy for women with small TNBC.

Conclusions:

Advancing age but not race/ethnicity was associated with lower likelihood of recommended treatment receipt among women with TNBC. Although omission of therapy among older patients with breast cancer may be appropriate in the case of smaller and lower risk TNBC, some were likely undertreated.
Adequacy of Initial Everolimus Dose, With and Without Calcineurin Inhibitors, in Kidney Transplant Recipients
Authors: Felipe Claudia , Ferreira Alexandra , Bessa Adrieli , Abait Tamiris , Perez Juliana D. , Casarini Dulce Elena , Medina-Pestana Jose , Tedesco Helio
Published: December 2017

Background:

This study investigates the adequacy of initial everolimus (EVR) dose, with and without calcineurin inhibitors (CNI), in kidney transplant recipients.

Methods:

This retrospective cohort analysis involved data from 305 kidney transplant recipients participating in 3 randomized trials receiving reduced dose cyclosporin A (CsA) combined with EVR 0.75 mg BID (CSA/EVR0.75, N = 32) or 1.5 mg BID (CSA/EVR1.5, N = 31), reduced dose tacrolimus (TAC) combined with EVR 1.5 mg BID (TAC0.05/EVR1.5, N = 83), standard dose TAC combined with EVR 1.5 mg BID (TAC0.1/EVR1.5, N = 93), and EVR 1.5 mg BID (EVR1.5, N = 66) with TAC introduction after day 5. The adequacy of the initial EVR dose, based on EVR whole blood trough between 3 and 8 ng/mL, was compared using first EVR blood concentrations obtained at day 3 after transplantation.

Results:

Recipient age, proportion of patients with diabetes mellitus, and proportion of grafts from living donors were different among the groups. Dose-corrected EVR concentrations were higher in patients receiving CsA than in those receiving TAC or no calcineurin inhibitors (6.7 ± 5.9 versus 5.4 ± 2.2 versus 2.4 ± 0.8 versus 2.5 ± 0.9 versus 2.2 ± 0.7, P = 0.000). No differences were observed comparing dose adjusted EVR concentrations combined with TAC or alone (P = 0.073). The proportion of patients with EVR concentration below <3 ng/mL was lower when EVR was combined with CsA (25 versus 3 versus 43 versus 33 versus 50%, P = 0.000). Later introduction of TAC did not influence EVR concentrations. There were no differences in mean CsA concentrations comparing patients receiving EVR 0.75 or 1.5 mg BID (240 ± 143 versus 213 ± 105 ng/mL). On the other hand, mean TAC concentrations were higher according to the initial TAC dose regimen (6.4 ± 3.9 versus 9.8 ± 5.9 ng/mL).

Conclusions:

In de novo kidney transplant recipients, the choice of the initial dose of EVR should consider the type of calcineurin inhibitor to reach target EVR concentration within the first week in a higher proportion of patients, maximizing the efficacy/toxicity profile.
Simulation of the Emergency Department Care Process for Pediatric Traumatic Brain Injury
Authors: Ajdari Ali , Boyle Linda Ng , Kannan Nithya , Wang Jin , Rivara Frederick P. , Vavilala Monica S.
Published: December 2017

The treatment of patients in the emergency department (ED) with severe pediatric traumatic brain injury (TBI) is challenging, and treatment process strategies that facilitate good outcomes are not well documented. The overall objective of this study was to identify factors that can affect the care process associated with pediatric TBI. This objective was achieved using a discrete-event simulation model of patients with TBI as they progress through the ED treatment process of a Level I trauma center. This model was used to identify areas where the ED length of stay can be reduced. The number of patients arriving at any given time was also varied in the simulation model to observe the impact to bed allocation policies and changes in staff and equipment. The findings showed that implementing changes in the ED (i.e., availability of two computerized tomography scanners, formation of resuscitation teams that included eight staff personnel, and modifying the bed allocation policy) could result in a 17% reduction in the mean ED length of stay. The study outcomes would be of interest to those (e.g., health administrators, health managers, and physicians) who can make decisions related to the treatment process in an ED.
Pediatric Adverse Event Rates Associated With Inexperience in Teaching Hospitals: A Multilevel Analysis
Authors: Dynan Linda , Goudie Anthony , Brady Patrick W.
Published: December 2017

High adverse event rates are a signal of potentially low-quality care that imposes burdens on patients, families, and hospitals. In this article, we examine the relationship between the distinct characteristics of teaching hospitals with adverse event rates among pediatric patients, controlling for patient complexity and severity using 2009–2011 Nationwide Inpatient Sample data from the Agency for Healthcare Research and Quality. We hypothesize that adverse event rates increase with the availability of more complex services and technologies (transplantation and pediatric open-heart surgery); increase as experience of providers decreases (July effect); and increase with residents per bed, a measure of both average provider inexperience and congestion. Using multilevel analysis, we find empirical evidence in support of our three hypotheses. We find that in environments where more learning occurs, more mistakes are made. Identifying high-performing hospitals with large residency programs and complex service lines that have made progress in patient safety and then studying how they have done so should become a priority. These findings should then be adapted within other hospitals through publicly funded mechanisms to improve the quality of care for all children.
Evaluation of a Dedicated Tobacco Cessation Support Service for Thoracic Cancer Center Patients
Authors: Amato Katharine A. , Reid Mary E. , Ochs-Balcom Heather M. , Giovino Gary A. , Bansal-Travers Maansi , Warren Graham W. , Mahoney Martin C. , Hyland Andrew J.
Published: December 2017

Context:

Cancer patients' continued tobacco use results in poorer therapeutic outcomes including decreased quality of life and survival.

Objective:

To assess reach and impact of a free, opt-out, telephone-based tobacco cessation program for thoracic cancer center patients.

Design:

Observational study.

Setting:

Comprehensive Cancer Center in Western New York.

Participants:

Current or recent (within past 30 days) tobacco-using thoracic cancer center patients referred to a tobacco cessation support service between October 2010 and October 2012 at a Comprehensive Cancer Center (n = 942/1313 referrals were eligible for cessation support).

Intervention:

A free, opt-out, telephone-based cessation service that was implemented as standard of care. Cessation specialists had patient-guided conversations that assessed readiness to quit; methods used in the past provided cessation strategies and worked to set up a quit date. There was an average of 35.9 days between referral and first contact.

Main Outcome Measures:

Program reach (referral and participation rates) and impact (as self-reported cessation outcomes measured twice after referral).

Results:

Of 942 patients, 730 (77.5%) referred to and called by a tobacco cessation service participated in at least 1 cessation support call, of which 440 of 730 (60.3%) were called for follow-up and 89.5% (394/440) participated. In total, 20.2% (69/342) of current smokers at referral reported at least 7-day abstinence at follow-up. Among current smokers at referral and first contact, being married (odds ratio [OR] = 2.05; 95% confidence interval [CI], 1.01-4.18) and having a lower Eastern Cooperative Oncology Group (ECOG) performance score (OR = 4.05; 95% CI, 1.58-10.39) were associated with quitting at follow-up, after controlling for demographic, clinical, and health behavior characteristics.

Conclusions:

Our results demonstrate that 78% of thoracic cancer center patients, if contacted, participated at least once in this cessation support service; for current smokers at referral and first contact, being married and having a lower ECOG performance score were associated with self-reported quitting at follow-up. Other organizations may find our results useful while implementing a systematic way to identify tobacco-using patients as part of routine care and to improve available cessation support services.
Brain Volumes and Longitudinal Cognitive Change
Authors: Vibha Deepti , Tiemeier Henning , Mirza Saira S. , Adams Hieab H.H. , Niessen Wiro J. , Hofman Albert , Prasad Kameshwar , van der Lugt Aad , Vernooij Meike W. , Ikram Mohammad A.
Published: December 2017

Objective:

To investigate the association of brain volumes, white matter lesion (WML) volumes, and lacunes, with cognitive decline in a population-based cohort of nondemented persons.

Methods:

Within the Rotterdam Study, 3624 participants underwent brain magnetic resonance imaging. Cognition was evaluated at baseline (2005 to 2009) and at the follow-up visit (2011 to 2013). We used a test battery that tapped into domains of executive function, information processing speed, motor speed, and memory. The volumetric measures assessed were total brain volume, lobar (gray matter and white matter) volumes, and hippocampal volumes. We also studied the association of WML volumes and lacunes with cognitive decline using linear regression models.

Results:

Total brain volume was associated with decline in global cognition, information processing, and motor speed (P<0.001) in analyses controlled for demographic and vascular factors. Specifically, smaller frontal and parietal lobes were associated with decline in information processing and motor speed, and smaller temporal and parietal lobes were associated with decline in general cognition and motor speed (P<0.001 for all tests). Total WML volume was associated with decline in executive function. Lobar WML volume, hippocampal volume, and lacunes were not associated with cognitive decline.

Conclusions:

Lower brain volume is associated with subsequent cognitive decline. Although lower total brain volume was significantly associated with decline in global cognition, specific lobar volumes were associated with decline in certain cognitive domains.
The current place of epilepsy surgery
Authors: Engel Jerome
Published: December 2017

Purpose of review

Three randomized controlled trials demonstrate that surgical treatment is safe and effective for drug-resistant epilepsy (DRE), yet fewer than 1% of patients are referred for surgery. This is a review of recent trends in surgical referral for DRE, and advances in the field. Reasons for continued underutilization are discussed.

Recent findings

Recent series indicate no increase in surgical referral for DRE over the past two decades. One study suggests that decreased referrals to major epilepsy centers can be accounted for by increased referrals to low-volume nonacademic hospitals where results are poorer, and complication rates higher. The increasing ability of high-resolution MRI to identify small neocortical lesions and an increase in pediatric surgeries, in part, explain a relative greater decrease in temporal lobe surgeries. Misconceptions continue to restrict referral. Consequently, advocacy for referral of all patients with DRE to epilepsy centers that offer specialized diagnosis and other alternative treatments, as well as psychosocial support, is recommended. Recent advances will continue to improve the safety and efficacy of surgical treatment and expand the types of patients who benefit from surgical intervention.

Surgical treatment for epilepsy remains underutilized, in part because of persistent misconceptions. Rather than promote referral for surgery, it would be more appropriate to advocate that all patients with DRE deserve a consultation at a full-service epilepsy center that offers many options for eliminating or reducing disability.
Quantifying biases in test-negative studies of vaccine effectiveness
Authors: Lewnard Joseph A. , Tedijanto Christine , Cowling Benjamin J. , Lipsitch Marc
Published: December 2017

Test-negative designs have become commonplace in assessments of seasonal influenza vaccine effectiveness. Vaccine effectiveness is measured from the exposure odds ratio (OR) of vaccination among individuals seeking treatment for acute respiratory illness and receiving a laboratory test for influenza infection. This approach is widely believed to correct for differential healthcare-seeking behavior among vaccinated and unvaccinated persons. However, the relation of the measured OR to true vaccine effectiveness is poorly understood. We derive the OR under circumstances of real-world test-negative studies. The OR recovers the true vaccine direct effect when two conditions are met: (1) that individuals’ vaccination decisions are uncorrelated with exposure or susceptibility to infection, and (2) that vaccination confers “all-or-nothing” protection (whereby certain individuals have no protection while others are perfectly protected). Biased effect size estimates arise if either condition is unmet. Such bias may suggest misleading associations of the OR with time since vaccination or the force of infection of influenza. The test-negative design may also fail to correct for differential healthcare-seeking behavior among vaccinated and unvaccinated persons without stringent criteria for enrollment and testing. Our findings demonstrate a need to reassess how data from test-negative studies are interpreted for policy decisions conventionally based on causal inferences.
Genome-Epigenome Interactions Associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Authors: Herrera Santiago , de Vega Wilfred C. , Ashbrook David , Vernon Suzanne D. , McGowan Patrick O.
Published: December 2017

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is an example of a complex disease of unknown etiology. Multiple studies point to disruptions in immune functioning in ME/CFS patients as well as with specific genetic polymorphisms and alterations of the DNA methylome in lymphocytes. However, the association between DNA methylation and genetic background in relation to the ME/CFS is currently unknown. In this study we explored this association by characterizing the genomic (~4.3 million SNPs) and epigenomic (~480 thousand CpG loci) variability between populations of ME/CFS patients and healthy controls. We found significant associations of methylation states in T-lymphocytes at several CpG loci and regions with ME/CFS phenotype. These methylation anomalies are in close proximity to genes involved with immune function and cellular metabolism. Finally, we found significant correlations of genotypes with methylation phenotypes associated with ME/CFS. The findings from this study highlight the role of epigenetic and genetic interactions in complex diseases, and suggest several genetic and epigenetic elements potentially involved in the mechanisms of disease in ME/CFS.
Comprehensive Cell Type Specific Transcriptomics of the Human Kidney
Authors: Sivakamasundari V , Bolisetty Mohan , Sivajothi Santhosh , Bessonett Shannon , Ruan Diane , Robson Paul
Published: December 2017

The human kidney is a complex organ composed of specialized cell types. To better define this cellular complexity, we profiled the individual transcriptomes of 22,469 normal human kidney cells, identifying 27 cell types. We describe three distinct endothelial cell populations, a novel subset of intercalated cells, interstitial macrophage and dendritic cells, and identify numerous novel cell-type-specific markers, many validated using imaging mass cytometry and immunohistochemistry. Receptor-ligand analysis revealed previously unknown intercalated-endothelial and intercalated-distal nephron interactions, suggesting a role in maintenance of vascular integrity and intercalated cell survival. Notably, kidney disease-associated genes were largely expressed in proximal tubules, podocytes, endothelial and myeloid cells, highlighting an underappreciated role for endothelial cells in kidney pathologies. Our analysis also provides a resource of cell type enriched markers, solute carriers, channels and lncRNAs. In summary, this cell-type-specific transcriptome resource provides the foundation for a comprehensive understanding of kidney function and dysfunction at single cell resolution.
Inferring Phylogenetic Networks Using PhyloNet
Authors: Wen Dingqiao , Yu Yun , Zhu Jiafan , Nakhleh Luay
Published: December 2017

PhyloNet was released in 2008 as a software package for representing and analyzing phylogenetic networks. At the time of its release, the main functionalities in PhyloNet consisted of measures for comparing network topologies and a single heuristic for reconciling gene trees with a species tree. Since then, PhyloNet has grown significantly. The software package now includes a wide array of methods for inferring phylogenetic networks from data sets of unlinked loci while accounting for both reticulation (e.g., hybridization) and incomplete lineage sorting. In particular, PhyloNet now allows for maximum parsimony, maximum likelihood, and Bayesian inference of phylogenetic networks from gene tree estimates. Furthermore, Bayesian inference directly from sequence data (sequence alignments or bi-allelic markers) is implemented. Maximum parsimony is based on an extension of the “minimizing deep coalescences” criterion to phylogenetic networks, whereas maximum likelihood and Bayesian inference are based on the multispecies network coalescent. All methods allow for multiple individuals per species. As computing the likelihood of a phylogenetic network is computationally hard, PhyloNet allows for evaluation and inference of networks using a pseudo-likelihood measure. PhyloNet summarizes the results of the various analyses, and generates phylogenetic networks in the extended Newick format that is readily viewable by existing visualization software, [phylogenetic networks; reticulation; incomplete lineage sorting; multispecies network coalescent; Bayesian inference; maximum likelihood; maximum parsimony.]
HNF1A is a Novel Oncogene and Central Regulator of Pancreatic Cancer Stem Cells
Authors: Abel Ethan V. , Goto Masashi , Magnuson Brian , Abraham Saji , Ramanathan Nikita , Hotaling Emily , Alaniz Anthony A. , Kumar-Sinha Chandan , Dziubinski Michele L. , Urs Sumithra , Wang Lidong , Shi Jiaqi , Waghray Meghna , Ljungman Mats , Crawford Howard C. , Simeone Diane M.
Published: December 2017

The biological properties of pancreatic cancer stem cells (PCSCs) remain incompletely defined and the central regulators are unknown. By bioinformatic analysis of a PCSC-enriched gene signature, we identified the transcription factor HNF1A as a putative central regulator of PCSC function. Levels of HNF1A and its target genes were found to be elevated in PCSCs and tumorspheres, and depletion of HNF1A resulted in growth inhibition, apoptosis, impaired tumorsphere formation, PCSC depletion, and downregulation of OCT4 expression. Conversely, HNF1A overexpression increased PCSC numbers and tumorsphere formation in pancreatic cancer cells and drove PDA cell growth. Importantly, depletion of HNF1A in primary tumor xenografts impaired tumor growth and depleted PCSCsin vivo. Finally, we established an HNF1A-dependent gene signature in PDA cells that significantly correlated with reduced survivability in patients. These findings identify HNF1A as a central transcriptional regulator of the PCSC state and novel oncogene in pancreatic ductal adenocarcinoma.
Algorithms for Search for Common Ancestors
Authors: Gitik Rita
Published: December 2017

Generation theory was developed as a tool for studying self-reproducing systems. In this paper we show that this theory can be applied to a search for common ancestors of living organisms.

We give two algorithms with flowcharts in pseudocode for finding common ancestors of a set of microbes and describe the connections with the genography problem.
Variations in δ13C of different plant organs: implications for post-photosynthetic fractionation
Authors: Zhang Yonge , Yu Xinxiao , Chen Lihua , Jia Guodong
Published: December 2017

Compared to photosynthetic fractionation, the mechanism of post-photosynthetic carbon isotope fractionation is not well understood. The aim of this study was to investigate post-photosynthetic fractionation in both above and below ground tissues and to evaluate potential hypotheses explaining differences in carbon isotope composition (δ13C) among different plant organs, which can provide valuable insights into plant physiology. The results revealed that there is no significant day-night difference inδ13C of twig phloem water soluble organic materials (WSOM), which could be explained by the unrestricted exchange of triose-phosphates between the chloroplast and cytoplasm and a time lag for carbohydrate exportation. Further, we found thatδ13C of twig phloem WSOM is more sensitive to plant water status than leaf WSOM. Analysis ofδ13C in different plant organs showed that the greatest13C enrichment was recorded in stem phloem. Divergences inδ13C of phloem WSOM among different plant organs were not likely to be explained by respiratory fractionation or time lag and were ascribed to transport of carbohydrates across organ boundaries and metabolic processes. Our study demonstrated that post-photosynthesis fractionation could not be ascribed to a single, unifying hypotheses; instead, it is the result of multiple processes.

Highlight

δ13C of twig phloem water soluble organic materials varied no clear diel pattern. In the leaf-twig-stem-root sequence, the greatest13C enrichment was recorded in stem phloem.
A simple spatially explicit neutral model explains range size distribution of reef fishes
Authors: Alzate Adriana , Janzen Thijs , Bonte Dries , Rosindell James , Etienne Rampal S.
Published: December 2017

Aim

The great variation in range sizes among species has fascinated ecologists for decades. In reef-associated fish species, which live in fragmented habitats and adopt a wide range of dispersal strategies, we may expect species with greater dispersal ability to spread over larger ranges. However, empirical evidence for such a positive relationship between dispersal and range size in reef fishes remains scarce. Here, we unveil the more nuanced role of dispersal on the range size distribution of reef associated fishes using empirical data and a novel spatially explicit model.

Location

Tropical Eastern Pacific

Major taxa studied

Reef-associated fishes

Methods

We estimated range size distributions for six different guilds of all reef-associated fishes with different dispersal abilities. We used a one-dimensional spatially explicit neutral model, which simulates the distribution of species along a linear coastline to explored the effect of dispersal, speciation and sampling on the distribution of range sizes. Our model adopts a more realistic gradual speciation process (protracted speciation) and incorporates important long distance dispersal events with a fat-tail dispersal kernel. We simulated our model using a highly efficient coalescence approach, which guarantees the metacommunity, is sampled at dynamic equilibrium. We fitted the model to the empirical data using an approximate Bayesian computation approach, with a sequential Monte Carlo algorithm.

Results

Stochastic birth, death, speciation and dispersal events alone can accurately explain empirical range size distributions for six different guilds of tropical, reef-associated fishes. Variation in range size distributions among guilds are explained purely by differences in dispersal ability with the best dispersers covering larger ranges.

Main conclusions

A simple combination of neutral processes with guild-specific dispersal ability provides a general explanation for both within- and across-guild range size variation. Our results support the theoretically expected, but empirically much debated, hypothesis that dispersal promotes range size.
Analysis of RDR1/RDR2/RDR6-independent small RNAs in Arabidopsis thaliana improves MIRNA annotations and reveals novel siRNA loci
Authors: Polydore Seth , Axtell Michael J.
Published: December 2017

Plant small RNAs regulate key physiological mechanisms through post-transcriptional and transcriptional silencing of gene expression. sRNAs fall into two major categories: those that are reliant on RNA Dependent RNA Polymerases (RDRs) for biogenesis and those that aren’t. Known RDR-dependent sRNAs include phased and repeat-associated short interfering RNAs, while known RDR-independent sRNAs are primarily microRNAs and other hairpin-derived sRNAs. In this study, we produced and analyzed small RNA-seq libraries from rdr1/rdr2/rdr6 triple mutant plants. Only a small fraction of all sRNA loci were RDR1/RDR2/RDR6-independent; most of these were microRNA loci or associated with predicted hairpin precursors. We found 58 previously annotated microRNA loci that were reliant on RDR1, −2, or −6 function, casting doubt on their classification. We also found 38 RDR1/2/6-independent small RNA loci that are not MIRNAs or otherwise hairpin-derived, and did not fit into other known paradigms for small RNA biogenesis. These 38 small RNA-producing loci have novel biogenesis mechanisms, and are frequently located in the vicinity of protein-coding genes. Altogether, our analysis suggest that these 38 loci represent one or more new types of small RNAs in Arabidopsis thaliana.

Significance Statement

Small RNAs regulate gene expression in plants and are produced through a variety of previously-described mechanisms. Here, we examine a set of previously undiscovered small RNA-producing loci that are produced by novel mechanisms.
CYRI1-mediated inhibition of RAC1 signalling restrictsSalmonellaTyphimurium infection
Authors: Yuki Kyoko E , Marei Hadir , Fiskin Evgenij , Eva Megan M , Gopal Angelica A , Schwartzentruber Jeremy A , Majewski Jacek , Cellier Mathieu , Mandl Judith N , Vidal Silvia M , Malo Danielle , Dikic Ivan
Published: December 2017

Salmonellapresents a global public health concern. Central toSalmonellapathogenicity is an ability to subvert host defence mechanisms through bacterial effectors that target key host proteins implicated in restricting infection. Thus, to gain insight into host-pathogen interactions governingSalmonellainfection, a thorough understanding of host defence mechanisms is needed. To tackle this, we performed anin vivogenome-wide ENU mutagenesis screen to uncover novel host defence proteins. Through this screen we identified an uncharacterised protein, which we name CYRI1 (CYFIP-relatedRAC1 Interacting protein1) that serves as aSalmonellaresistance factor. We show that CYRI1 binds to the small GTPase RAC1 through a conserved domain present in CYFIP proteins, which are known RAC1 effectors that stimulate actin polymerisation. However, unlike CYFIP proteins, CYRI1 negatively regulates RAC1-driven actin cytoskeleton remodelling, thereby attenuating processes such as phagocytosis and cell migration. This, in turn, enables CYRI1 to counteractSalmonellaat various stages of infection, including bacterial entry into epithelial cells, internalisation into myeloid-derived phagocytes as well as phagocyte-mediated bacterial dissemination. Together, this outlines a novel host defence mechanism that is crucial for determining bacterial fate.
Emergence of reward expectation signals in identified dopamine neurons
Authors: Coddington Luke T. , Dudman Joshua T.
Published: December 2017

Coherent control of purposive actions emerges from the coordination of multiple brain circuits during learning. Dissociable brain circuits and cell-types are thought to preferentially participate in distinct learning mechanisms. For example, the activity of midbrain dopamine (mDA) neurons is proposed to primarily, or even exclusively, reflect reward prediction error signals in well-trained animals. To study the specific contribution of individual circuits requires observing changes before tight functional coordination is achieved. However, little is known about the detailed timing of the emergence of reward-related representations in dopaminergic neurons. Here we recorded activity of identified dopaminergic neurons as naïve mice learned a novel stimulus-reward association. We found that at early stages of learning mDA neuron activity reflected both external (sensory) and internal (action initiation) causes of reward expectation. The increasingly precise correlation of action initiation with sensory stimuli rather than an evaluation of outcomes governed mDA neuron activity. Thus, our data demonstrate that mDA neuron activity early in learning does not reflect errors, but is more akin to a Hebbian learning signal - providing new insight into a critical computation in a highly conserved, essential learning circuit.
Experimental Evolution Across Different Thermal Regimes Yields Genetic Divergence in Recombination Fraction But No Divergence in Temperature-Associated Plastic Recombination
Authors: Kohl Kathryn P. , Singh Nadia D.
Published: December 2017

Phenotypic plasticity is pervasive in nature. One mechanism underlying the evolution and maintenance of such plasticity is environmental heterogeneity. Indeed, theory indicates that both spatial and temporal variation in the environment should favor the evolution of phenotypic plasticity under a variety of conditions. Cyclical environmental conditions have also been shown to yield evolved increases in recombination frequency. Here were use a panel of replicated experimental evolution populations ofD. melanogasterto test whether variable environments favor enhanced plasticity in recombination rate and/or increased recombination rate in response to temperature. In contrast to expectation, we find no evidence for either enhanced plasticity in recombination or increased rates of recombination in the variable environment lines. Our data confirm a role of temperature in mediating recombination fraction inD. melanogaster, and indicate that recombination is genetically and plastically depressed under lower temperatures. Our data further suggest that the genetic architectures underlying plastic recombination and population-level variation in recombination rate are likely to be distinct.
Routine habitat switching alters the likelihood and persistence of infection with a pathogenic parasite
Authors: Daversa David R. , Manica Andrea , Bosch Jaime , Jolles Jolle W. , Garner Trenton W. J.
Published: December 2017

Animals switch habitats on a regular basis, and when habitats vary in suitability for parasitism, routine habitat switching alters the frequency of parasite exposure and may affect post‐infection parasite proliferation. However, the effects of routine habitat switching on infection dynamics are not well understood.

We performed infection experiments, behavioural observations and field surveillance to evaluate how routine habitat switching by adult alpine newts (Ichthyosaura alpestris) influences infection dynamics of the pathogenic parasite,Batrachochytrium dendrobatidis(Bd).

We show that when newts are exposed to equal total doses ofBdin aquatic habitats,differences in exposure frequency and post‐exposure habitat alter infection trajectories: newts developed more infections that persisted longer when doses were broken into multiple, reduced‐intensity exposures. Intensity and persistence of infections were reduced among newts that were switched to terrestrial habitats following exposure.

When presented with a choice of habitats, newts did not avoid exposure toBd, but heavily infected newts were more prone to reduce time spent in water.

Accounting for routine switching between aquatic and terrestrial habitat in the experiments generated distributions of infection loads that were consistent with those in two populations of wild newts.

Together, these findings emphasize that differential habitat use and behaviours associated with daily movement can be important ecological determinants of infection risk and severity.

Aplain language summaryis available for this article.
Exploring the perceived usefulness of practical food groups in day treatment for individuals with eating disorders
Authors: Biddiscombe Rachel J. , Scanlan Justin Newton , Ross Jessica , Horsfield Sarah , Aradas Jessica , Hart Susan
Published: December 2017

Background/aim

Recovery from eating disorders is a challenging process. Emerging literature suggests that occupational therapists may provide a useful contribution in delivering purposeful eating‐related interventions as a potential treatment to support sustained cognitive and behavioural changes for individuals with eating disorders. This study aimed to evaluate participants’ perceptions of the contribution of occupational therapy practical food groups (food based outings and cooking groups) in supporting their functional recovery.

Methods

Individuals attended practical food groups as part of standard treatment at an outpatient eating disorders day program. Ninety‐nine participants completed questionnaires at discharge and up to three follow‐up points (6, 12 and 24 months). Questions related to practical food groups were analysed, exploring participants’ experiences and perceived usefulness of groups using rating‐scale and open‐ended questions. Open‐ended responses were analysed using thematic analysis. Descriptive statistics were calculated for responses to rating‐scale questions.

Results

At discharge, participants rated the importance and usefulness of practical food groups as high (4.73 and 4.43 on 5‐point scales, respectively), but tended to rate their enjoyment of the groups lower (3.50 on a 5‐point scale). Some skill transfer was typically reported by participants at discharge (3.92 on a 5‐point scale). One core theme, ‘success through participation’, emerged from qualitative comments. Six subthemes were also identified: helpful components of practical food groups; perceived benefit of exposure; impact of applying cognitive and behavioural skills; challenges affecting participation; facilitating adaptation; and influence of eating disorders on challenging feared foods.

Conclusion

This study highlights that participation in practical food groups was perceived as useful in assisting individuals to improve eating behaviours and, in some circumstances, transfer these skills into their lives outside of day program. Results suggest that occupational therapists may have an important contribution in delivering these interventions to support recovery and facilitate application of adaptive coping strategies.
Using the cognitive interviewing process to improve survey design by allied health: A qualitative study
Authors: Howlett Owen , McKinstry Carol , Lannin Natasha A.
Published: December 2017

Background/aim

Allied health professionals frequently use surveys to collect data for clinical practice and service improvement projects. Careful development and piloting of purpose‐designed surveys is important to ensure intended measuring (that respondents correctly interpret survey items when responding). Cognitive interviewing is a specific technique that can improve the design of self‐administered surveys. The aim of this study was to describe the use of the cognitive interviewing process to improve survey design, which involved a purpose‐designed, online survey evaluating staff use of functional electrical stimulation.

Methods

A qualitative study involving one round of cognitive interviewing with three occupational therapists and three physiotherapists.

Results

The cognitive interviewing process identified 11 issues with the draft survey, which could potentially influence the validity and quality of responses. The raised issues included difficulties with: processing the question to be able to respond, determining a response to the question, retrieving relevant information from memory and comprehending the written question. Twelve survey amendments were made following the cognitive interviewing process, comprising four additions, seven revisions and one correction.

Conclusions

The cognitive interviewing process applied during the development of a purpose‐designed survey enabled the identification of potential problems and informed revisions to the survey prior to its use.
Immediate post‐insertion tip migration of peripherally inserted central catheters dependent on arm position and depth of inspiration
Authors: De Carvalho Bruno R , Eagar Gerard M
Published: December 2017

Introduction

The purpose of this study is to assess the degree of PICC tip migration with breathing and arm movement to determine whether accurate positioning is feasible or futile.

Methods

A prospective cohort of 218 consecutive patients undergoing PICC insertion at our institution between January and August 2015 was selected, of which 129 met inclusion criteria. The position of insertion was used as control with the arm at 90° during inspiration, followed by three study images: expiration with arm unchanged, inspiration with arm fully adducted and inspiration with arm fully abducted. Mean and standard deviations (SD) of change in PICC position were determined. ANOVA, Pearson correlation coefficients and Chi‐square tests were used to assess the effects of vessel choice, PICC calibre and angle of arm abduction. Complications were recorded.

Results

Movement was predominantly caudal with a mean of 10.4 mm (SD 16.5) with similar degrees of movement in the expiration (12.3 mm) and adduction (12.9 mm) views (P = 0.709). Arm abduction resulted in a mean caudal movement of 6.5 mm. (SD 18.6); however, the degree of abduction had no predictable effect on PICC movement. Thirty‐two per cent of cases demonstrated movement into the right atrium. Neither vessel choice nor type of PICC was shown to have a significant effect on PICC movement.

Conclusion

There is large amplitude of PICC tip position change with depth of inspiration and arm position resulting in frequent right atrial position. Despite this there were no associated complications in our cohort which compliments emerging international opinion regarding intra‐atrial PICC tip position.
Under‐utilisation of high‐dose‐rate brachytherapy boost in men with intermediate‐high risk prostate cancer treated with external beam radiotherapy
Authors: Ong Wee Loon , Evans Sue M , Millar Jeremy L
Published: December 2017

Introduction

The aim of this study was to evaluate the use of high‐dose‐rate brachytherapy (HDR‐BT) boost with definitive external beam radiotherapy (EBRT) in prostate cancer (CaP) management.

Methods

The study population comprised men with intermediate‐high risk CaP captured in the population‐based Prostate Cancer Outcome Registry Victoria (PCOR‐Vic), treated with EBRT from January 2010 to December 2015. The primary outcome is the proportion of men who received HDR‐BT boost. Multivariate logistic regressions were used to evaluate the effect of patient‐, tumour‐ and treatment‐factors on the likelihood of HDR‐BT use. Medicare Benefit Schedule (MBS) data was accessed to evaluate the Australia‐wide pattern of HDR‐BT use.

Results

One thousand eight hundred and six patients were included in this study – 886 (49%) intermediate‐risk, and 920 (51%) high‐risk CaP patients. Overall, only 124 (7%) patients had EBRT + HDR‐BT – 47 (5%) intermediate‐risk and 77 (8%) high‐risk CaP patients (P = 0.01). There is higher proportion of patients who had HDR‐BT in public institutions (7% public vs. 3% private, P = 0.005) and in metropolitan centres (9% metropolitan vs. 2% regional, P < 0.001). In multivariate analyses, older patients were less likely to have HDR‐BT (OR = 0.92; 95% CI = 0.89–0.94, P < 0.001), while patients with high‐risk CaP (OR = 1.8; 95% CI = 1.3–2.7; P = 0.002) treated in metropolitan centres (OR = 5.0; 95% CI = 2.6–9.8; P < 0.001) and public institutions (OR = 3.8; 95% CI = 1.5–9.4; P = 0.005) were more likely to have EBRT + HDR‐BT. There was significant decline in numbers of HDR‐BT performed throughout Australia, from 313 cases in 2010 to 125 cases in 2015.

Conclusion

High‐dose‐rate brachytherapy is under‐utilised with EBRT in this contemporary population‐based cohort of Victorian men with CaP. The decline in HDR‐BT use was also observed nationally.
Are early‐life antecedents of suicide mortality associated with psychiatric disorders and suicidal ideation in midlife?
Authors: Geoffroy M.‐C. , Gunnell D. , Clark C. , Power C.
Published: December 2017

Objective

To establish whether previously identified early‐life antecedents of suicide mortality (i.e. low birthweight, younger maternal age, higher birth order, externalizing problems and adversities) are associated with proximal psychiatric disorders and suicidal ideation, which are themselves associated with an increased risk of suicide.

Methods

Participants were from the 1958 British birth‐cohort (N = 8905) with information on prenatal/childhood experiences and the Clinical Interview Schedule‐Revised at age 45 years. Outcomes were as follows: any internalizing disorder (anxiety disorder/depressive episode), depressive episode, alcohol use disorder and suicidal ideation.

Results

After adjustment, higher birth order (Ptrend = 0.043), younger maternal age (Ptrend = 0.017) and increased number of childhood adversities (Ptrend = 0.026) were associated with an increased risk of internalizing disorders. For example, the OR (95% CI) in fourth‐ or later‐born children was 1.48 (1.06–2.07) and for young maternal age (<19 years) was 1.31 (0.89–1.91). Effect sizes were similar in magnitude for depressive episode and suicidal ideation, although associations did not reach conventional significance levels. No associations were found for low birthweight and externalizing problems (in males) and investigated outcomes.

Conclusion

Associations for younger maternal age, higher birth order and adversities with adult internalizing disorders suggest that psychiatric disorders may be on the pathway linking some early‐life factors and suicide.