bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolutionary dynamics of neoantigens in growing tumours
Authors: Lakatos Eszter , Williams Marc J. , Schenck Ryan O. , Cross William C. H. , Househam Jacob , Werner Benjamin , Gatenbee Chandler , Robertson-Tessi Mark , Barnes Chris P. , Anderson Alexander R. A. , Sottoriva Andrea , Graham Trevor A.
Published: February 2019

Cancer evolution is driven by the acquisition of somatic mutations that provide cells with a beneficial phenotype in a changing microenvironment. However, mutations that give rise to neoantigens, novel cancer–specific peptides that elicit an immune response, are likely to be disadvantageous. Here we show how the clonal structure and immunogenotype of growing tumours is shaped by negative selection in response to neoantigenic mutations. We construct a mathematical model of neoantigen evolution in a growing tumour, and verify the model using genomic sequencing data. The model predicts that, in the absence of active immune escape mechanisms, tumours either evolve clonal neoantigens (antigen– ‘hot’), or have no clonally– expanded neoantigens at all (antigen– ‘cold’), whereas antigen– ‘warm’ tumours (with high frequency subclonal neoantigens) form only following the evolution of immune evasion. Counterintuitively, strong negative selection for neoantigens during tumour formation leads to an increased number of antigen– warm or – hot tumours, as a consequence of selective pressure for immune escape. Further, we show that the clone size distribution under negative selection is effectively– neutral, and moreover, that stronger negative selection paradoxically leads to more neutral– like dynamics. Analysis of antigen clone sizes and immune escape in colorectal cancer exome sequencing data confirms these results. Overall, we provide and verify a mathematical framework to understand the evolutionary dynamics and clonality of neoantigens in human cancers that may inform patient– specific immunotherapy decision– making.
Curriculum-based outdoor learning for children aged 9-11: A qualitative analysis of pupils’ and teachers’ views
Authors: Marchant Emily , Todd Charlotte , Cooksey Roxanne , Dredge Samuel , Jones Hope , Reynolds David , Stratton Gareth , Dwyer Russell , Lyons Ronan , Brophy Sinead
Published: February 2019

The relationship between child health, wellbeing and education demonstrates that healthier and happier children achieve higher educational attainment. An engaging curriculum that facilitates children in achieving their academic potential has strong implications for educational outcomes, future employment prospects and health and wellbeing during adulthood. Outdoor learning is a pedagogical approach used to enrich learning, enhance school engagement and improve pupil health and wellbeing. However, its non-traditional means of achieving curricular aims are not yet recognised beyond the early years by education inspectorates. This requires evidence into its acceptability from those at the forefront of delivery. This study aimed to explore headteachers’, teachers’ and pupils’ views and experiences of an outdoor learning programme within the key stage two curriculum (ages 9-11). We examine the process of implementation to offer case study evidence through 1:1 interviews with headteachers (n=3) and teachers (n=10) and focus groups with pupils aged 9-11 (n=10) from three primary schools. Interviews and focus groups were conducted at baseline and six months into implementation. Schools introduced regular outdoor learning within the curriculum. This study found a variety of perceived benefits for pupils and schools. Pupils and teachers noticed improvements in pupils’ engagement with learning, concentration and behaviour, as well as positive impacts on health and wellbeing and teachers’ job satisfaction. Curriculum demands including testing and evidencing work were barriers to implementation, in addition to safety concerns, resources and teacher confidence. Participants supported outdoor learning as a curriculum-based programme for older primary school pupils. However, embedding outdoor learning within the curriculum requires education inspectorates to place higher value on this approach in achieving curricular aims, alongside greater acknowledgment of the wider benefits to children which current measurements do not capture.
Cooperative population coding facilitates efficient sound source separability by adaptation to spatial statistics
Authors: Gleiss Helge , Encke Jörg , Lingner Andrea , Jennings Todd R. , Brosel Sonja , Kunz Lars , Grothe Benedikt , Pecka Michael
Published: February 2019

Our sensory environment changes constantly. Accordingly, neural systems continually adapt to the concurrent stimulus statistics to remain sensitive over a wide range of conditions. Such dynamic range adaptation (DRA) is assumed to increase both the effectiveness of the neuronal code and perceptual sensitivity. However, direct demonstrations of DRA-based efficient neuronal processing that also produces perceptional benefits are lacking. Here we investigated the impact of DRA on spatial coding in the rodent brain and the perception of human listeners. Naturalistic spatial stimulation with dynamically changing source locations elicited prominent DRA already on the initial spatial processing stage, the Lateral Superior Olive (LSO) of gerbils of either sex. Surprisingly, on the level of individual neurons, DRA diminished spatial tuning due to large response variability across trials. However, when considering single-trial population averages of multiple neurons, DRA enhanced the coding efficiency specifically for the concurrently most probable source locations. Intrinsic LSO population imaging of energy consumption combined with pharmacology revealed that a slow-acting LSO gain control mechanism distributes activity across a group of neurons during DRA, thereby enhancing population coding efficiency. Strikingly, such “efficient cooperative coding” also improved neuronal source separability specifically for the locations that were most likely to occur. These location-specific enhancements in neuronal coding were paralleled by human listeners exhibiting a selective improvement in spatial resolution. We conclude that, contrary to canonical models of sensory encoding, the primary motive of early spatial processing is efficiency optimization of neural populations for enhanced source separability in the concurrent environment.

Author summary

The renowned efficient coding hypothesis suggests that neural systems adapt their processing to the statistics of the environment to maximize information while minimizing the underlying energetic costs. It is further assumed that such neuronal adaptations also confer perceptual advantages. Yet direct demonstrations of adaptive mechanisms or strategies that result both in increased neuronal coding efficiency and perceptual benefits are lacking. Here we show that an auditory spatial processing circuit exploits slow-acting gain control to distribute activity across the neuronal population, thereby enhancing coding efficiency based on single-trial population averages. This population-efficiency maximization also results in improved neuronal spatial resolution for the concurrently most probable source locations, which was resembled in a focally improved spatial acuity of human listeners.
Do damaging variants of SLC6A9, the gene for the glycine transporter 1 (GlyT-1), protect against schizophrenia?
Authors: Curtis David
Published: February 2019

Aims

To test whether genetic variants predicted to impair the functionality of SLC6A9, which codes for the GlyT-1 glycine transporter, are protective against schizophrenia.

Method

In an exome sequenced sample of 4225 schizophrenia cases and 5834 controls variants occurring in SLC6A9 were annotated and weights were assigned using GENEVARASSOC. Genotype counts were compared using SCOREASSOC.

Results

Variants predicted to be deleterious by SIFT and damaging by PolyPhen were examined. Genotypes at 1:44466494-G/A seemed likely to be erroneous. If these were ignored then there were 15 damaging variants in controls and 5 in cases.

Conclusions

The results are consistent with the hypothesis that variants which damage SLC6A9 are protective against schizophrenia but a larger sample would be required to confirm this.

Declaration of interest

The author declares no conflict of interest.
The scaling of expansive energy under the Red Queen predicts Cope’s Rule
Authors: Žliobaitė Indrė , Fortelius Mikael
Published: February 2019

The Red Queen’s hypothesis portrays evolution as a never-ending competition for expansive energy, where one species’ gain is another species’ loss. The Red Queen is neutral with respect to body size, implying that neither small nor large species have a universal competitive advantage. The maximum population growth in ecology; however, clearly depends on body size – the smaller the species, the shorter the generation length, and the faster it can expand. Here we ask whether, and if so how, the Red Queen’s hypothesis can accommodate a spectrum of body sizes. We theoretically analyse scaling of expansive energy with body mass and demonstrate that in the Red Queen’s zero-sum game for resources, neither small nor large species have a universal evolutionary advantage. We argue that smaller species have an evolutionary advantage only when resources in the environment are not fully occupied, such as after mass extinctions or following key innovations allowing expansion into freed up or previously unoccupied resource space. Under such circumstances, we claim, generation length is the main limiting factor for population growth. When competition for resources is weak, smaller species can indeed expand faster, but to sustain this growth they also need more resources. In the Red Queen’s realm, where resources are fully occupied and the only way for expansion is to outcompete other species, acquisition of expansive energy becomes the limiting factor and small species lose their physiological advantage. A gradual transition from unlimited resources to a zero-sum game offers a direct mechanistic explanation for observed body mass trends in the fossil record, known as Cope’s Rule. When the system is far from the limit of resources and competition is not maximally intense, small species take up ecological space faster. When the system approaches the limits of its carrying capacity and competition tightens, small species lose their evolutionary advantage and we observe a wider range of successful body masses, and, as a result, an increase in the average body mass within lineages.
A Polygenic Score for Body Mass Index is Associated with Depressive Symptoms via Early Life Stress: Evidence for gene-environment correlation
Authors: Avinun Reut , Hariri Ahmad R.
Published: February 2019

Background

Increasing childhood overweight and obesity rates are associated with not only adverse physical, but also mental health outcomes, including depression. These negative outcomes may be caused and/or exacerbated by the bullying and shaming overweight individuals experience. As body mass index (BMI) can be highly heritable, we hypothesized that a genetic risk toward higher BMI, will predict higher early life stress (ELS), which in turn will predict higher depressive symptoms in adulthood. Such a process will reflect an evocative gene-environment correlation (rGE) wherein an individual’s genetically influenced phenotype evokes a reaction from the environment that subsequently shapes the individual’s health.

Methods

We modeled genetic risk using a polygenic score of BMI derived from a recent large GWAS meta-analysis. Self-reports were used for the assessment of ELS and depressive symptoms in adulthood. The discovery sample consisted of 524 non-Hispanic Caucasian university students from the Duke Neurogenetics Study (DNS; 278 women, mean age 19.78±1.23 years) and the independent replication sample consisted of 5 930 white British individuals from the UK biobank (UKB; 3 128 women, mean age 62.66±7.38 years).

Results

A significant mediation effect was found in the DNS (indirect effect=.207, bootstrapped SE=.10, 95% CI: .014 to .421), and then replicated in the UKB (indirect effect=.04, bootstrapped SE=.01, 95% CI: .018 to .066). Higher BMI polygenic scores were associated with higher depressive symptoms through the experience of higher ELS.

Conclusions

Our findings suggest that evocative rGE may contribute to weight-related mental health problems and stress the need for interventions that aim to reduce weight bias, specifically during childhood.
Cortical tracking of speech reveals top-down reconstructive processes
Authors: Mukherjee Sankar , Tomassini Alice , Badino Leonardo , Pastore Aldo , Fadiga Luciano , D’Ausilio Alessandro
Published: February 2019

Cortical entrainment to the (quasi-) rhythmic components of speech seems to play an important role in speech comprehension. It has been suggested that neural entrainment may reflect top-down temporal predictions of sensory signals. Key properties of a predictive model are its anticipatory nature and its ability to reconstruct missing information. Here we put both these two properties to experimental test. We acoustically presented sentences and measured cortical entrainment to both acoustic speech envelope and lips kinematics acquired from the speaker but not visible to the participants. We then analyzed speech-brain and lips-brain coherence at multiple negative and positive lags. Besides the well-known cortical entrainment to the acoustic speech envelope, we found significant entrainment in the delta range to the (latent) lips kinematics. Most interestingly, the two entrainment phenomena were temporally dissociated. While entrainment to the acoustic speech peaked around +0.3 s lag (i.e., when EEG followed speech by 0.3 s), entrainment to the lips was significantly anticipated and peaked around 0-0.1 s lag (i.e., when EEG was virtually synchronous to the putative lips movement). Our results demonstrate that neural entrainment during speech listening involves the anticipatory reconstruction of missing information related to lips movement production, indicating its fundamentally predictive nature and thus supporting analysis by synthesis models.
The genomic architecture of competitive response of Arabidopsis thaliana is highly flexible between monospecific and plurispecific neighborhoods
Authors: Libourel Cyril , Baron Etienne , Lenglet Juliana , Amsellem Laurent , Roby Dominique , Roux Fabrice
Published: February 2019

Although plants simultaneously interact with multiple neighboring species throughout their life cycle, there is still very limited information about the genetics of the competitive response in the context of plurispecific interactions. Using a local mapping population of Arabidopsis thaliana, we set up a Genome Wide Association study to estimate the extent of genetic variation of the competitive response in presence of 12 plant species assemblages, and to compare the genetic architecture of the competitive response between monospecific and plurispecific neighborhoods. Based on four phenotypic traits, we detected strong crossing reaction norms not only among the three monospecific neighborhoods, but also among the different plant assemblages. Accordingly, the genetic architecture of the competitive response was highly dependent on the identity and the relative abundance of the neighboring species. In addition, enriched biological processes underlying the competitive response largely differ between monospecific and plurispecific neighborhoods. In particular, receptor-like kinases and transporters were significantly enriched in plurispecific neighborhoods. Our results suggest that plants can integrate and respond to different species assemblages depending on the identity and number of each neighboring species, through a large range of genes associated mainly with perception and signaling processes leading to developmental and stress responses.
A human photoacoustic imaging reporter gene using the clinical dye indocyanine green
Authors: Nyström Nivin N. , Yip Lawrence C.M. , Carson Jeffrey J.L. , Scholl Timothy J. , Ronald John A.
Published: February 2019

Photoacoustic imaging (PAI) combines optical contrast with the resolution and depth-detection of ultrasound and is increasingly being utilized for medical imaging in patients. PAI reporter genes would allow for monitoring of cell and gene therapies, but current reporters have immunogenicity and/or toxicity concerns that may limit clinical translation. Here we report a PAI reporter system employing the ability of humanorganic anion transporting polypeptide 1b3(Oatp1b3) to take up the clinical dye indocyanine green (ICG) into cells. Following ICG administration, cells synthetically expressingOatp1b3exhibited significantly increased PAI signals compared to control cells bothin vitroand in mice. Several benefits of this technology are the human derivation ofOatp1b3, and the high extinction coefficient, low quantum yield and pre-existing clinical approval of ICG. We posit that theOatp1b3-ICG reporter system could be useful forin vivogene and cell tracking in preclinical and clinical applications.
Increasing Synaptic GluN2B levels within the Basal and Lateral Amygdala Enables the Modification of Strong Reconsolidation Resistant Fear Memories
Authors: Solis Christopher A. de , Gonzalez Cuauhtémoc U. , Galdamez Mario A. , Perish John M. , Woodard Samuel W. , Salinas Carlos E. , Miller Joel N. , Elahi Hajira , Pineda Oziel H. , Oad Shayrin , las Fuentes Serafin Gatica de , Owen Malissa S. , Sandoval Alfredo , Holehonnur Roopashri , Ploski Jonathan E.
Published: February 2019

Reconsolidation disruption has been proposed as a method to attenuate pathological memories in disorders such as PTSD. However, studies from our group and others indicate that strong memories are resistant to becoming destabilized following reactivation, rendering them impervious to agents that disrupt the re-stabilization phase of reconsolidation. Thus, therapies designed to attenuate maladaptive memories by disrupting reconsolidation updating have not been adequately developed. We previously determined that animals possessing strong auditory fear memories, compared to animals with weaker fear memories, are associated with an enduring increase in the synaptic GluN2A/GluN2B ratio in neurons of the mouse basal and lateral amygdala (BLA). In this study, we determined whether increasing GluN2B levels within BLA excitatory neuronal synapses is sufficient to enable modification of strong fear memories via reconsolidation. To accomplish this, we utilized a combinatorial genetic strategy to express GluN2B or GluN2B(E1479Q) in excitatory neurons of the mouse BLA before or after fear memory consolidation. GluN2B(E1479Q) contains a point mutation that increases synaptic expression of the subunit by interfering with phosphorylation-driven endocytosis. At the time of memory retrieval, increasing synaptic GluN2B levels by expression of GluN2B(E1479Q), butnotGluN2B(WT), enhanced the induction of reconsolidation rendering the strong fear memory modifiable. GluN2B(WT) or GluN2B(E1479Q) expression did not influence fear memory maintenance or extinction. Fear memory consolidation, however, was enhanced when GluN2B(E1479Q) was expressed in the BLA at the time of training. These findings indicate that enhancing GluN2B synaptic trafficking may provide a novel therapeutic strategy to enhance modification of pathological memories.
Effectiveness of Genomic Selection by Response to Selection for Winter Wheat Variety Improvement
Authors: Hu Xiaowei , Carver Brett F. , Powers Carol , Yan Liuling , Zhu Lan , Chen Charles
Published: February 2019

The genomic revolution opened up the possibility for predicting un-tested phenotypes in schemes commonly referred as genomic selection (GS). Considering the practicality of applying GS in the line development stage of a hard red winter (HRW) wheat variety development program (VDP), effectiveness of GS was evaluated by prediction accuracy, as well as by the response to selection across field seasons that demonstrated challenges for crop improvement under significant climate variability. Important breeding targets for HRW wheat improvement in the southern Great Plains of USA, including Grain Yield, Kernel Weight, Wheat Protein content, and Sodium Dodecyl Sulfate (SDS) Sedimentation Volume as a rapid test for predicting bread-making quality, were used to estimate GS’s effectiveness across harvest years from 2014 (drought) to 2016 (normal). In general, nonparametric algorithms RKHS and RF produced higher accuracies in both same-year/environment cross validations and cross-year/environment predictions, for the purpose of line selection in this bi-parental doubled haploid (DH) population. Further, the stability of GS performance was greatest for SDS Sedimentation Volume but least for Wheat Protein content. To ensure long-term genetic gain, our study on selection response suggested that across this sample of environmental variability, and though there are cases where phenotypic selection (PS) might be still preferential, training conducted under drought stress or in suboptimal conditions could still provide an encouraging prediction outcome, when selection decisions were made in normal conditions. However, it is not advisable to use training information collected from a normal field season to predict trait performance under drought conditions. Further, the superiority of response to selection was most evident if the training population can be optimized.

Core Ideas

Prediction performance for winter wheat grain yield and end-use quality traits.

Prediction accuracy evaluated by cross validations significantly overestimated.

Non-parametric algorithms outperform, when considering cross-year predictions.

Strategically designing training population improves response to selection.

Response to selection varied across growing seasons/environments.
Sonic hedgehog signaling in astrocytes mediates cell type-specific synaptic organization
Authors: Hill Steven , Blaeser Andrew , Coley Austin A. , Xie Yajun , Shepard Katherine A. , Harwell Corey C. , Gao Wen-Jun , Garcia A. Denise R.
Published: February 2019

Astrocytes have emerged as integral partners with neurons in regulating synapse formation and function, but the mechanisms that mediate these interactions are not well understood. Here, we show that Sonic hedgehog (Shh) signaling between neurons and astrocytes is required for establishing structural organization and remodeling of cortical synapses in a cell type-specific manner. In the postnatal cortex, Shh signaling is active in a subpopulation of mature astrocytes localized primarily in deep cortical layers. Selective disruption of Shh signaling in astrocytes produces a dramatic increase in synapse number specifically on layer V apical dendrites that emerges during adolescence and persists into adulthood. Dynamic turnover of dendritic spines is impaired in mutant mice and is accompanied by an increase in neuronal excitability and a reduction of the glial-specific, inward-rectifying K+ channel Kir4.1. These data identify a critical role for Shh signaling in astrocyte-mediated modulation of neuronal activity required for sculpting synapses.
Freeze-frame imaging of synaptic activity using SynTagMA
Authors: Perez-Alvarez Alberto , Fearey Brenna C. , Schulze Christian , O’Toole Ryan J. , Moeyaert Benjamien , Mohr Manuel A. , Arganda-Carreras Ignacio , Yang Wei , Wiegert J. Simon , Schreiter Eric R. , Gee Christine E. , Hoppa Michael B. , Oertner Thomas G.
Published: February 2019

Information within the brain travels from neuron to neuron across synapses. At any given moment, only a few synapses within billions will be active and are thought to transmit key information about the environment, a behavior being executed or memory being recalled. Here we present SynTagMA, which marks active synapses within a ~2 s time window. Upon violet illumination, the genetically expressed tag converts from green to red fluorescence if bound to calcium. Targeted to presynaptic terminals, preSynTagMA allows discrimination between active and silent axons. Targeted to excitatory postsynapses, postSynTagMA creates a snapshot of synapses active just before photoconversion. To analyze large datasets, we developed an analysis program that automatically identifies and tracks the fluorescence of thousands of individual synapses in tissue. Together, these tools provide a high throughput method for repeatedly mapping active synapses in vitro and in vivo.
Synaptotagmin-1 and Doc2b exhibit distinct membrane remodeling mechanisms
Authors: Sorkin Raya , Marchetti Margherita , Logtenberg Emma , Piontek Melissa , Kerklingh Emma , Brand Guy , Voleti Rashmi , Rizo Josep , Roos Wouter H. , Groffen Alexander J. , Wuite Gijs J. L.
Published: February 2019

While the role of Synaptotagmin-1 in living cells has been described in detail, it remains a challenge to dissect the contribution of membrane remodelling by its two cytoplasmic C2 domains (C2AB) to the Ca2+-secretion coupling mechanism. Here, we study membrane remodeling using pairs of optically-trapped beads coated with SNARE-free synthetic membranes. We find that the soluble C2AB domain of Syt1 strongly affects the probability and strength of membrane-membrane interactions in a strictly Ca2+- and protein-dependent manner. A lipid mixing assay with confocal imaging reveals that at low Syt1 concentrations, no hemifusion is observed. Notably, for similar low concentrations of Doc2b hemifusion does occur. Consistently, both C2AB fragments cause a reduction in the membrane bending modulus, as measured by an AFM-based method. This lowering of the energy required for membrane deformation likely contributes to the overall Ca2+-secretion triggering mechanism by calcium sensor proteins. When comparing symmetrical (both sides) and asymmetrical (one side) presence of protein on the membranes, Syt1 favors an asymmetrical but Doc2b a symmetrical configuration, as inferred from higher tether probabilities and break forces. This provides support for the direct bridging hypothesis for Syt-1, while hinting to possible preference for protein-protein (and not protein-membrane) interactions for Doc2b. Overall, our study sheds new light on the mechanism of Ca2+ induced fusion triggering, which is essential for fundamental understanding of secretion of neurotransmitters and endocrine substances.
Polymerase Chain Reaction (PCR) Amplification of GC-Rich Templates
Authors: Green Michael R. , Sambrook Joseph
Published: February 2019

The efficiency of polymerase chain reaction (PCR) amplification is influenced by the nucleotide composition and sequence of the template DNA. Problematic templates include those with long homopolymeric runs, inverted repeats, or GC-rich tracts—such as those containing >60% G + C residues—that are found in the regulatory regions of many mammalian genes. Localized regions of templates rich in GC residues tend to fold into complex secondary structures that might not melt during the annealing phase of the PCR cycle. Also, the primers used to amplify GC-rich regions often have a high capacity to form self- and cross-dimers and a strong tendency to fold into stem–loop structures that can impede the progress of the DNA polymerase along the template molecule. Predictably, amplification of full-length template DNA is inefficient, and the products of the reaction contain a high proportion of shorter molecules that result from blockage of the DNA polymerase. Altering the design of the primers and using a combination of hot start and touchdown PCR can sometimes improve the efficiency of amplification. More often, a multipronged approach is required, such as the use of enhancers in the amplification reaction, adjustment of the cycling protocol, and, if necessary, designing new sets of primers. This protocol uses a mixture of four additives—betaine, dithiothreitol (DTT), dimethyl sulfoxide (DMSO), and bovine serum albumin (BSA)—for use with Taq DNA polymerase.
Isolation of DNA Fragments from Polyacrylamide Gels by the Crush and Soak Method
Authors: Green Michael R. , Sambrook Joseph
Published: February 2019

The standard method to recover fragments of DNA from polyacrylamide gels is the “crush and soak” technique. The eluted DNA is generally free of contaminants that inhibit enzymes or that are toxic to transfected or microinjected cells. The method requires time but little labor and results in recovery of <30%–90%, depending on the size of the DNA fragment. It can be used to isolate both double-stranded and single-stranded DNAs from neutral and denaturing polyacrylamide gels, respectively. The method is widely used to isolate synthetic oligonucleotides from denaturing polyacrylamide gels. DNA recovered from polyacrylamide gels by crushing and soaking is generally suitable for use as a hybridization probe, as a polymerase chain reaction (PCR) primer, and as a substrate in enzyme-catalyzed reactions.
Mapping of individual dislocations with dark-field X-ray microscopy
Authors: Jakobsen A. C. , Simons H. , Ludwig W. , Yildirim C. , Leemreize H. , Porz L. , Detlefs C. , Poulsen H. F.
Published: February 2019

This article presents an X-ray microscopy approach for mapping deeply embedded dislocations in three dimensions using a monochromatic beam with a low divergence. Magnified images are acquired by inserting an X-ray objective lens in the diffracted beam. The strain fields close to the core of dislocations give rise to scattering at angles where weak beam conditions are obtained. Analytical expressions are derived for the image contrast. While the use of the objective implies an integration over two directions in reciprocal space, scanning an aperture in the back focal plane of the microscope allows a reciprocal-space resolution of ΔQ/Q < 5 × 10−5 in all directions, ultimately enabling high-precision mapping of lattice strain and tilt. The approach is demonstrated on three types of samples: a multi-scale study of a large diamond crystal in transmission, magnified section topography on a 140 µm-thick SrTiO3 sample and a reflection study of misfit dislocations in a 120 nm-thick BiFeO3 film epitaxially grown on a thick substrate. With optimal contrast, the half-widths at half-maximum of the dislocation lines are 200 nm.
Deflection analysis of the airship structure based on the tapered inflatable beam
Authors: Chen Zheng , Zhao Haitao , Li Xiaowang , Chen Ji’an
Published: February 2019

Purpose

The purpose of this paper is to analyse the deflection of the flexible airship structure in a new way which can decrease the calculation amount and improve the calculation speed.

Design/methodology/approach

Infinitesimal method and tapered inflatable beam theory are combined to study the mechanics characteristics of the airship. Firstly, infinitesimal method is introduced into the airship structure analysis. The airship structure can be divided into several tapered inflatable beam elements. Then, tapered inflatable beam theory is improved and a developed model of the tapered inflatable beam under bending moment is presented. Besides, it is proved that deflection caused by pure load and pure moment can be linearly superimposed. Finally, the deflection of the airship structure is studied by means of tapered inflatable beam theory.

Findings

This paper improved the tapered inflatable beam theory. Besides, the proposed method for deflection analysis of the flexible airship in this paper can reach the same accuracy with traditional finite element method (FEM). However, the number of beam elements is much less than the one of FEM shell elements, which will decrease the calculation amount much and improve the calculation speed.

Practical implications

The flexible airship is a new and developing research area in engineering practice. The proposed method in this paper provides one precise and high-speed way to analyse the deformation of the airship.

Originality/value

The paper draws its value from the contributions to development of inflatable structure and the flexible airship mechanics research.
Time and the spectral other: Demonstrating against ‘Unite the Right 2’
Authors: STARRETT GREGORY , DALSHEIM JOYCE
Published: February 2019

Recent public protests against right‐wing politics in the United States have often demonstrated a sense of surprise at the recurrence of racist, anti‐Semitic and fascist ideologies and movements which ought to belong to the past. Using insights from Walter Benjamin, Johannes Fabian and Jacques Derrida, the authors analyze the recent gathering of thousands of counter‐demonstrators at the ‘Unite the Right 2’ rally in Washington, DC and discuss how political and moral enemies are rhetorically consigned to another time. The temporality on display at this demonstration was more complex than linear, progressive time. Instead, it consolidated events from the past, present and future into a sense of eternal and recurrent victory. They argue that this temporality is an expression both of Derrida’s ideas about spectrality and Tanya Luhrmann’s analysis of the moral psychology of faith.
A Test of Sex Estimation in Subadults Using the Elevation of the Auricular Surface from Four Samples of Known Age and Sex
Authors: Blake Kathleen A.S.
Published: February 2019

Biological sex is foundational to the work of forensic anthropologists and bioarcheologists. The lack of reliable biological sex estimation methods for subadults has, thus, greatly limited forensic and bioarcheological analyses. Auricular surface elevation showed promise as a subadult sex estimation method in previous studies. This study examined two auricular surface elevation evaluation methods on four subadult samples of known age, sex, and ancestry. Samples were scored as “male,” “female,” or “indeterminate” and results were examined with chi‐square analysis. No consistent sex estimation pattern, accuracy, or predictive value was produced between samples. Only one test was significant using Fisher's exact test analysis (FET = 7.501, p < 0.022): the composite approach on the Hamann‐Todd sample. While age, sample size, or developmental factors may play a role in these results, clearly sample variation does as well. This study found auricular surface elevation was not a useful subadult sex estimation method.
Adhesion of Bread Dough to Solid Surfaces Under Controlled Heating: Balance Between the Rheological and Interfacial Properties of Dough
Authors: Huault Lucie , Vésinet Manon , Brogly Maurice , Giampaoli Pierre , Bistac Sophie , Bosc Véronique
Published: February 2019

The adhesion of wheat dough affects many aspects of industrial baking, from kneading raw dough to the final baking process. In this work, an original method was developed to study the effect of temperature on the adhesive properties of bread dough in contact with a solid surface during heating. Using this approach, it will be possible to understand the factors that affect adhesion between dough and a baking surface, which will aid in developing methods to prevent dough from sticking. Overall, the dough's adhesion to a hydrophobic surface globally decreased with an increase in temperature from 35 to 97 °C, with the exception of the temperature range between 55 and 70 °C, in which the energy of adhesion increased slightly. Under these circumstances, the evolution of adhesion was primarily shaped by the rheological properties of the dough. However, when we used a solid surface with different surface energy, the results changed significantly, which suggests that the mechanisms of adhesion during heating are governed by a balance between the interfacial and bulk properties of the heated dough. The overall decrease in the adhesion of the dough to the hydrophobic glass surface may be explained by a decrease in dough hydrophobicity due to structural and chemical changes in the dough.
Characteristics and long‐term outcomes of advanced pleural mesothelioma in Latin America (MeSO‐CLICaP)
Authors: Rojas Leonardo , Cardona Andrés F. , Trejo‐Rosales Rogelio , Zatarain‐Barrón Zyanya Lucia , Ramírez‐Tirado Laura‐Alejandra , Ruiz‐Patiño Alejandro , Campos Gómez Saúl , Corrales Luis , Oblitas George , Bacon Ludwing , Martín Claudio , de Lima Vladmir C. Cordeiro , Freitas Helano C. , Mas Luis , Vargas Carlos , Carranza Hernán , Otero Jorge , Pérez María Angelina , González Lisde , Chirinos Luis , Granados Sara T. , Rodriguez July , Báez Renata , Remolina Bonilla Yuly‐Andrea , Núñez Cerrillo Gustavo , Archila Pilar , Cuello Mauricio , Karachaliou Niki , Rosell Rafael , Arrieta Oscar ,   on behalf CLICaP
Published: February 2019

Background

Malignant pleural mesothelioma (MPM) is an aggressive tumor, associated with poor prognosis. There is a lack of information about the clinical and pathological features related with survival in the Latin American population.

Methods

The MeSO‐CLICaP registry identified 302 patients with advanced MPM diagnosed and treated between January 2008 and March 2016. The Cox model was applied to determine the variables associated with survival. A random forest tree model was built to predict the response to first‐line chemotherapy among Latin American patients.

Results

The median age was 61.1 years (SD 10.6 years), 191 (63.2%) were men, 65.9% were ever smokers, and 38.7% had previous exposure to asbestos. A total of 237 (78.5%) had epithelioid tumors, and 188 (62.3%) and 114 (37.7%) cases had stage III or IV MPM, respectively. A total of 49 patients (16.2%) underwent pleurectomy, 57 (18.9%) received radiotherapy, and 279 patients received first‐line platinum‐based chemotherapy. The overall response rate to first‐line chemotherapy was 40.4%, progression‐free survival to first‐line treatment was 5.7 months (95% CI 4.9–6.5), and 63 (20.8%) patients had pemetrexed maintenance. The median overall survival was 16.8 months (95% CI 13.0–20.5), and multivariate analysis found that stage (P = 0.013), and pleurodesis (P = 0.048), were independent prognostic factors for first‐line overall survival. The model to predict response to first‐line chemotherapy obtained a 0.98 area under the curve, a sensitivity of 93%, and a specificity of 95% for detecting responders and non‐responders.

Conclusion

This study identifies factors associated with clinical benefit from chemotherapy among advanced MPM Latin American patients, emphasizing the impact of histology and the clinical benefit of chemotherapy on outcomes.
HIF1α‐mediated AIMP3 suppression delays stem cell aging via the induction of autophagy
Authors: Kim Chul , Park Ji‐Min , Song Youngsook , Kim Sunghoon , Moon Jisook
Published: February 2019

Senescence in stem cells, which occurs as a consequence of chronic responses to the environment, defines the capacity of stem cells for proliferation and differentiation as well as their potential for tissue regeneration and homeostasis maintenance. Although stem cells reside under low oxygen pressure and the availability of oxygen is known to be a crucial determinant in their fate, the key modulators in stem cell aging and the underlying mechanism have yet to be unraveled. Human placenta‐derived mesenchymal stem cells (hpMSCs) were cultured under hypoxia (3% O2) or normoxia (21% O2) to investigate the key factors that regulate stem cell senescence under hypoxic conditions. RNA sequencing results suggested that the expression of aminoacyl‐tRNA synthetase‐interacting multifunctional protein 3 (AIMP3, EEF1E1), an aging inducer, in the hpMSCs was dramatically repressed under hypoxia with concurrent suppression of the aging marker p16INK4a. The hpMSCs that overexpressed AIMP3 under hypoxic conditions displayed significantly decreased proliferation and fewer stem cell characteristics, whereas the downregulation of AIMP3 ameliorated the age‐related senescence of MSCs. Consistent with the results of the hpMSCs, MSCs isolated from the adipose tissue of AIMP3‐overexpressing mice exhibited decreased stem cell functions. Interestingly, AIMP3‐induced senescence is negatively regulated by hypoxia‐inducible factor 1α (HIF1α) and positively regulated by Notch3. Furthermore, we showed that AIMP3 enhanced mitochondrial respiration and suppressed autophagic activity, indicating that the AIMP3‐associated modulation of metabolism and autophagy is a key mechanism in the senescence of stem cells and further suggesting a novel target for interventions against aging.
Drinking and Intimate Partner Violence Severity Levels Among U.S. Ethnic Groups in an Urban Emergency Department
Authors: Caetano Raul , Cunradi Carol B. , Alter Harrison J. , Mair Christina , Yau Rebecca K.
Published: February 2019

Background

Emergency departments (EDs) provide care to ethnically diverse populations with multiple health‐related risk factors, many of which are associated with intimate partner violence (IPV). This paper examines ethnic‐specific 12‐month rates of physical IPV by severity and their association with drinking and other sociodemographic and personality correlates in an urban ED sample.

Methods

Research assistants surveyed patients at an urban ED regarding IPV exposure as well as patterns of alcohol and drug use, psychological distress, adverse childhood experiences (ACEs), and other sociodemographic features.

Results

The survey (N = 1,037) achieved an 87.5% participation rate. About 23% of the sample reported an IPV event in the past 12 months. Rates were higher (p < 0.001) among blacks (34%), whites (31%), and multiethnic (46%) respondents than those among Asians (13%) and Hispanics (15%). Modeled results showed that black respondents were more likely than Hispanics (reference) to report IPV (adjusted odds ratio [AOR] = 1.69, 95% confidence interval [CI] = 1.98–2.66, p < 0.05) and that respondents’ partner drinking was associated with IPV (AOR = 1.85, 95% CI = 1.25–2.73, p < 0.01) but respondents’ drinking was not. Use of illicit drugs, younger age, impulsivity, depression, partner problem drinking, ACEs, and food insufficiency were all positively associated with IPV.

Conclusions

There was considerable variation in IPV rates across ethnic groups in the sample. The null results for the association between respondents’ drinking and IPV was surprising and may stem from the relatively moderate levels of drinking in the sample. Results for ethnicity, showing blacks as more likely than Hispanics to report IPV, support prior literature.
Composite pronator quadratus: radial forearm free flap in functional lip reconstruction
Authors: Grinsell Damien , Herle Pradyumna
Published: February 2019

Background

Reconstruction of lip defects following neoplasia and trauma is a common procedure in plastic surgery. Reconstruction of large lip defects is a difficult undertaking and some degree of residual functional impairment and disability are likely to occur. Microsurgical reconstruction is the recommended technique for large lip defects; however, limitations exist regarding optimal aesthetic and functional outcomes with current free flap options.

Method

We propose a new composite flap design based on the innervated pronator quadratus with the radial forearm free flap for a more dynamic reconstruction of total or near total lip defects. Results of our series of four patients have been reviewed.

Results

The radial forearm flap – innervated pronator quadratus flap has been used in four patients thus far for lip reconstruction. This flap, in our limited series has shown excellent results in achieving oral competence, good motor function and acceptable cosmetic appearance.

Conclusion

The composite radial forearm–pronator quadratus flap is a promising new lip reconstruction technique that has potential to provide a higher level of oral competence, sphincteric function and symmetrical lip movement, than current microsurgical options in dynamic lip reconstruction. This method warrants further investigation in plastic surgery literature.
Weekend effect: analysing temporal trends in solid organ donation
Authors: Hedley James A. , Chang Nicholas , Kelly Patrick J. , Rosales Brenda M. , Wyburn Kate , O'Leary Michael , Cavazzoni Elena , Webster Angela C.
Published: February 2019

Background

Research suggests patients treated over weekends experience poorer outcomes. Only one US‐based study explored this weekend effect in organ donation, specifically the kidney discard rate. In Australia potential donors are referred to a donation service, and donation proceeds if family consent is granted and the donor is deemed medically suitable to donate. Organ procurement occurs when utilization is almost certain hence discard rates are much lower than in the USA. We aimed to characterize the effect of weekend referral on organ donation in Australia.

Methods

We retrospectively reviewed all New South Wales Organ and Tissue Donation Service logs from 2010 to 2016. Our primary outcome was progression to organ procurement, and secondary outcomes were family consent and meeting medical suitability thresholds. We used logistic regression with random effects adjusting for clustering of referral hospitals.

Results

Of 3496 potential donors referred for consideration, 694 (20%) progressed to organ procurement. There were fewer referrals on weekends (average 415 versus 588 for weekdays). However, donation rates were no lower for weekend compared to weekday referrals (adjusted OR 1.17; 95% CI 0.95, 1.44). Family consent (adjusted OR 1.20; 95% CI 1.00, 1.44) and medical suitability (adjusted OR 1.15; 95% CI 0.96, 1.38) were not lower for weekend compared to weekday referrals. Similar results were found for all sensitivity analyses conducted.

Conclusions

In Australia, the donation pathway operates consistently throughout the week, with donation no less likely to proceed on weekends and holidays. This finding contrasts with findings in the USA.
National trends in surgical therapy for benign prostatic hyperplasia in Australia
Authors: Patel Rohan M. , Bariol Simon
Published: February 2019

Background

To determine national trends in the utilization of surgical procedures for the treatment of benign prostatic hyperplasia (BPH) in Australia over the last 20 years.

Methods

The Medicare Australia and Australian Institute of Health and Welfare databases were used to determine the annual number of surgical procedures and hospital admissions for BPH.

Results

From 1998 to 2017, surgical procedures for BPH have increased by 79% which is largely commensurate with population growth. From 1998 to 2008, transurethral resection of the prostate (TURP) was the predominant surgical therapy, accounting for 96% of all surgical treatments. From 2008 to 2017, TURP use reduced to 70% and in the last 5 years has been replaced with photoselective vaporization (16%), UroLift (8%) and holmium laser prostatectomy (6%). UroLift is used significantly more in younger men (P < 0.001).

Conclusion

There has been a substantial increase in surgical treatments for BPH over the last 20 years. In the last 5 years, TURP use has declined due to an increase in laser prostatectomy and UroLift procedures.
Geographies of co‐production: Learning from inclusive research approaches at the margins
Authors: Holt Louise , Jeffries Jayne , Hall Edward , Power Andrew
Published: February 2019

This introduction to the themed special issue raises provocative questions about the nature and meaning of co‐production by engaging specifically with voices from the margins – groups and individuals who occupy marginalised embodied subjectivities. Key themes emerging from the papers raise questions about the nature and meaning of co‐production. We suggest a need to move away from a focus on co‐production or even participation towards empowerment and inclusivity. We urge researchers to be explicit about the meaning of the terms “participation” or “co‐production” to think critically about the “communities” with whom we research and how research forges positive social change.