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Dust samples were collected from Irish homes. House Dust Mite and storage mites were separated from the dust. The microbiome and resistome of mites and originating dust were assessed using a culture-independent approach. The bacterial microbiome of mites and dust were predominantly populated by Staphylococci. There was a highly significant (P = 0.005; Spearman's rank test) correlation between the bacterial microbiome of mites and the dust. One-hundred and eighteen antimicrobial resistance genes (ARGs) were associated with mites and 176 with dust. Both contained ARGs encoding resistance for multi drug resistances, macrolide-lincosamide-streptogramin B, mobile genetic elements, Beta-lactam, Tetracycline and Aminoglycosides. By contrast, 15 ARGs were found for a laboratory-grown strain of Dermatophagoides pteronyssinus. A significant difference (P = 0.03; t test) was found in means between the resistome of mites and the household dust from which they emanated. No significant correlations (P = 0.23 and P = 0.22; Mantel test) were observed between the microbiome and resistome of mite and dust samples. There was not a significant difference (P = 0.54; t-test) between the means of ARGs for homes with and without a history of antibiotic use. [ABSTRACT FROM AUTHOR]

The Epidermal Growth Factor Receptor (EGFR) is frequently found to be mutated in non-small cell lung cancer. Oncogenic EGFR has been successfully targeted by tyrosine kinase inhibitors, but acquired drug resistance eventually overcomes the efficacy of these treatments. Attempts to surmount this therapeutic challenge are hindered by a poor understanding of how and why cancer mutations specifically amplify ligand-independent EGFR auto-phosphorylation signals to enhance cell survival and how this amplification is related to ligand-dependent cell proliferation. Here we show that drug-resistant EGFR mutations manipulate the assembly of ligand-free, kinase-active oligomers to promote and stabilize the assembly of oligomer-obligate active dimer sub-units and circumvent the need for ligand binding. We reveal the structure and assembly mechanisms of these ligand-free, kinase-active oligomers, uncovering oncogenic functions for hitherto orphan transmembrane and kinase interfaces, and for the ectodomain tethered conformation of EGFR. Importantly, we find that the active dimer sub-units within ligand-free oligomers are the high affinity binding sites competent to bind physiological ligand concentrations and thus drive tumor growth, revealing a link with tumor proliferation. Our findings provide a framework for future drug discovery directed at tackling oncogenic EGFR mutations by disabling oligomer-assembling interactions. The Epidermal Growth Factor Receptor (EGFR) is frequently found to be mutated in non-small cell lung cancer. Here, the authors show that EGFR lung cancer mutations promote the assembly of kinase-active dimers within ligand-free EGFR oligomers. These dimers bind ligand with high affinity and promote tumor growth. [ABSTRACT FROM AUTHOR]

Data Science advances in sports commonly involve "big data", i.e., large sport-related data sets. However, such big data sets are not always available, necessitating specialized models that apply to relatively few observations. One important area of sport-science research that features small data sets is the study of recovery from exercise. In this area, models are typically fitted to data collected from exhaustive exercise test protocols, which athletes can perform only a few times. Recent findings highlight that established recovery models such as the so-called work-balance models are too simple to adequately fit observed trends in the data. Therefore, we investigated a hydraulic model that requires the same few data points as work-balance models to be applied, but promises to predict recovery dynamics more accurately. To compare the hydraulic model to established work-balance models, we retrospectively applied them to data compiled from published studies. In total, one hydraulic model and three work-balance models were compared on data extracted from five studies. The hydraulic model outperformed established work-balance models on all defined metrics, even those that penalize models featuring higher numbers of parameters. These results incentivize further investigation of the hydraulic model as a new alternative to established performance models of energy recovery. [ABSTRACT FROM AUTHOR]

Open data on biological invasions are particularly critical in regions that are co-governed and/or where multiple independent parties have responsibility for preventing and controlling invasive alien species. The Antarctic is one such region where, in spite of multiple examples of invasion policy and management success, open, centralised data are not yet available. This dataset provides current and comprehensive information available on the identity, localities, establishment, eradication status, dates of introduction, habitat, and evidence of impact of known introduced and invasive alien species for the terrestrial and freshwater Antarctic and Southern Ocean region. It includes 3066 records for 1204 taxa and 36 individual localities. The evidence indicates that close to half of these species are not having an invasive impact, and that ~ 13% of records are of species considered locally invasive. The data are provided using current biodiversity and invasive alien species data and terminology standards. They provide a baseline for updating and maintaining the foundational knowledge needed to halt the rapidly growing risk of biological invasion in the region. [ABSTRACT FROM AUTHOR]

Background: Mental health disorders are a common sequelae of traumatic brain injury (TBI) and are associated with worse health outcomes including increased mental health care utilization. The objective of this study was to determine the association between TBI and use of mental health services in a population-based sample. Methods: Using data from a national Canadian survey, this study evaluated the association between TBI and mental health care utilization, while adjusting for confounding variables. A log-Poisson regression model was used to estimate unadjusted and adjusted prevalence ratios (PR) and 95% confidence intervals (CI). Results: The study sample included 158,287 TBI patients and 25,339,913 non-injured individuals. Compared with those were not injured, TBI patients reported higher proportions of chronic mental health conditions (27% vs. 12%, p < 0.001) and heavy drinking (33% vs. 24%, p = 0.005). The adjusted prevalence of mental health care utilization was 60% higher in patients with TBI than those who were not injured (PR = 1.60, 95%; CI 1.05–2.43). Conclusions: This study suggests that chronic mental health conditions and heavy drinking are more common in individuals with TBI. The prevalence of mental health care utilization is 60% higher in TBI patients compared with those who are not injured after adjusting for sociodemographic factors, mental health conditions, and heavy drinking. Future longitudinal research is required to examine the temporality and direction of the association between TBI and the use of mental health services. [ABSTRACT FROM AUTHOR]

The human skin barrier, a biological imperative, is impaired in inflammatory skin diseases such as atopic dermatitis (AD). Staphylococcus aureus is associated with AD lesions and contributes to pathological inflammation and further barrier impairment. S. aureus secretes extracellular proteases, such as V8 (or 'SspA'), which cleave extracellular proteins to reduce skin barrier. Previous studies demonstrated that the host defence peptide human beta-defensin 2 (HBD2) prevented V8-mediated damage. Here, the mechanism of HBD2-mediated barrier protection in vitro is examined. Application of exogenous HBD2 provided protection against V8, irrespective of timeline of application or native peptide folding, raising the prospect of simple peptide analogues as therapeutics. HBD2 treatment, in context of V8-mediated damage, modulated the proteomic/secretomic profiles of HaCaT cells, altering levels of specific extracellular matrix proteins, potentially recovering V8 damage. However, HBD2 alone did not substantially modulate cellular proteomic/secretomics profiles in the absence of damage, suggesting possible therapeutic targeting of lesion damage sites only. HBD2 did not show any direct protease inhibition or induce expression of known antiproteases, did not alter keratinocyte migration or proliferation, or form protective nanonet structures. These data validate the barrier-protective properties of HBD2 in vitro and establish key protein datasets for further targeted mechanistic analyses. [ABSTRACT FROM AUTHOR]

Helical structures are ubiquitous in nature and impart unique mechanical properties and multifunctionality1. So far, synthetic architectures that mimic these natural systems have been fabricated by winding, twisting and braiding of individual filaments1–7, microfluidics8,9, self-shaping1,10–13 and printing methods14–17. However, those fabrication methods are unable to simultaneously create and pattern multimaterial, helically architected filaments with subvoxel control in arbitrary two-dimensional (2D) and three-dimensional (3D) motifs from a broad range of materials. Towards this goal, both multimaterial18–23 and rotational24 3D printing of architected filaments have recently been reported; however, the integration of these two capabilities has yet to be realized. Here we report a rotational multimaterial 3D printing (RM-3DP) platform that enables subvoxel control over the local orientation of azimuthally heterogeneous architected filaments. By continuously rotating a multimaterial nozzle with a controlled ratio of angular-to-translational velocity, we have created helical filaments with programmable helix angle, layer thickness and interfacial area between several materials within a given cylindrical voxel. Using this integrated method, we have fabricated functional artificial muscles composed of helical dielectric elastomer actuators with high fidelity and individually addressable conductive helical channels embedded within a dielectric elastomer matrix. We have also fabricated hierarchical lattices comprising architected helical struts containing stiff springs within a compliant matrix. Our additive-manufacturing platform opens new avenues to generating multifunctional architected matter in bioinspired motifs.A 3D printing platform comprising a rotational multimaterial printhead is demonstrated, enabling the fabrication of helically architected filaments and lattices with programmable subvoxel control. [ABSTRACT FROM AUTHOR]

Aquatic biotelemetry increasingly relies on using acoustic transmitters ('tags') that enable passive detection of tagged animals using fixed or mobile receivers. Both tracking methods are resource-limited, restricting the spatial area in which movements of highly mobile animals can be measured using proprietary detection systems. Transmissions from tags are recorded by underwater noise monitoring systems designed for other purposes, such as cetacean monitoring devices, which have been widely deployed in the marine environment; however, no tools currently exist to decode these detections, and thus valuable additional information on animal movements may be missed. Here, we describe simple hybrid methods, with potentially wide application, for obtaining information from otherwise unused data sources. The methods were developed using data from moored, acoustic cetacean detectors (C-PODs) and towed passive receiver arrays, often deployed to monitor the vocalisations of cetaceans, but any similarly formatted data source could be used. The method was applied to decode tag detections that were found to have come from two highly mobile fish species, bass (Dicentrarchus labrax) and Twaite shad (Alosa fallax), that had been tagged in other studies. Decoding results were validated using test tags; range testing data were used to demonstrate the relative efficiency of these receiver methods in detecting tags. This approach broadens the range of equipment from which acoustic tag detections can be decoded. Novel detections derived from the method could add significant value to past and present tracking studies at little additional cost, by providing new insights into the movement of mobile animals at sea. [ABSTRACT FROM AUTHOR]

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are structurally complex natural products with diverse bioactivities. Here we report discovery of a RiPP, kintamdin, for which the structure is determined through spectroscopy, spectrometry and genomic analysis to feature a bis-thioether macrocyclic ring and a β-enamino acid residue. Biosynthetic investigation demonstrated that its pathway relies on four dedicated proteins: phosphotransferase KinD, Lyase KinC, kinase homolog KinH and flavoprotein KinI, which share low homologues to enzymes known in other RiPP biosynthesis. During the posttranslational modifications, KinCD is responsible for the formation of the characteristic dehydroamino acid residues including the β-enamino acid residue, followed by oxidative decarboxylation on the C-terminal Cys and subsequent cyclization to provide the bis-thioether ring moiety mediated by coordinated action of KinH and KinI. Finally, conserved genomic investigation allows further identification of two kintamdin-like peptides among the kin-like BGCs, suggesting the occurrence of RiPPs from actinobacteria. The chemical diversity of peptides from ribosomal origin is a growing field of research. Here, the authors report the discovery, genomic and biosynthetic investigations of kintamdin, a ribosomally synthesized and post-translationally modified peptides featuring a beta-enamino acid and a bis-thioether macrocyclic motif. [ABSTRACT FROM AUTHOR]

Large-scale human genetic data1–3 have shown that cancer mutations display strong tissue-selectivity, but how this selectivity arises remains unclear. Here, using experimental models, functional genomics and analyses of patient samples, we demonstrate that the lineage transcription factor paired box 8 (PAX8) is required for oncogenic signalling by two common genetic alterations that cause clear cell renal cell carcinoma (ccRCC) in humans: the germline variant rs7948643 at 11q13.3 and somatic inactivation of the von Hippel-Lindau tumour suppressor (VHL)4–6. VHL loss, which is observed in about 90% of ccRCCs, can lead to hypoxia-inducible factor 2α (HIF2A) stabilization6,7. We show that HIF2A is preferentially recruited to PAX8-bound transcriptional enhancers, including a pro-tumorigenic cyclin D1 (CCND1) enhancer that is controlled by PAX8 and HIF2A. The ccRCC-protective allele C at rs7948643 inhibits PAX8 binding at this enhancer and downstream activation of CCND1 expression. Co-option of a PAX8-dependent physiological programme that supports the proliferation of normal renal epithelial cells is also required for MYC expression from the ccRCC metastasis-associated amplicons at 8q21.3-q24.3 (ref. 8). These results demonstrate that transcriptional lineage factors are essential for oncogenic signalling and that they mediate tissue-specific cancer risk associated with somatic and inherited genetic variants.The lineage transcription factor PAX8 is shown to play a pivotal part in determining cancer risk in clear cell renal cell carcinoma, providing insights into how genetic mutations lead to specific types of cancer. [ABSTRACT FROM AUTHOR]

Aptamers are artificial oligonucleotides binding to specific molecular targets. They have a promising role in therapeutics and diagnostics but are often difficult to design. Here, we exploited the catRAPID algorithm to generate aptamers targeting TAR DNA-binding protein 43 (TDP-43), whose aggregation is associated with Amyotrophic Lateral Sclerosis. On the pathway to forming insoluble inclusions, TDP-43 adopts a heterogeneous population of assemblies, many smaller than the diffraction-limit of light. We demonstrated that our aptamers bind TDP-43 and used the tightest interactor, Apt-1, as a probe to visualize TDP-43 condensates with super-resolution microscopy. At a resolution of 10 nanometers, we tracked TDP-43 oligomers undetectable by standard approaches. In cells, Apt-1 interacts with both diffuse and condensed forms of TDP-43, indicating that Apt-1 can be exploited to follow TDP-43 phase transition. The de novo generation of aptamers and their use for microscopy opens a new page to study protein condensation. Here, the authors generated an artificial RNA molecule, or aptamer, specific for the Amyotrophic Lateral Sclerosis protein TDP-43. By interacting avidly with its target, the aptamer can be exploited to track TDP-43 phase transition in vitro and in cells. [ABSTRACT FROM AUTHOR]

With the myriad theories generated through research over the years, a continuing challenge for researchers is to navigate the multitude of theories in order to communicate their research, integrate empirical results, and make progress as a field by building upon empirical research. The Social Unit of Learning project was purposefully designed so that researchers from multiple disciplines with different theoretical perspectives could work together to examine the complexity of the mathematics classroom. In this paper, we reflect on the multiple analytical accounts generated from the project, drawing from the notions of complementarity and commensurability. Two parallel analyses, applying the commognitive framework and the theory of representations respectively, are used as illustrative examples for discussion regarding complementarity and commensurability. The paper addresses two focal questions, as follows: in what ways do divergence or contradiction in incommensurable analytical accounts reflect methodological discrepancies or fundamental differences in the underpinning theories? Furthermore, in what ways do the accounts generated by the parallel analyses predicated on different theories lead to differences in instructional advocacy? The answers to these questions provide empirically-grounded insights into the consideration of incommensurability in educational research, and suggest ways in which researchers and practitioners might apply the notion of complementarity to reconcile or exploit incommensurable analytical accounts that have resulted in different instructional advocacies. [ABSTRACT FROM AUTHOR]

The majority of geographical profiling research focuses on the relationship between offender and location, which works particularly well when a burial site is known. In real-world investigations, however, burial or dump sites are often not known. The aim of the current paper is to outline a relatively under-used method of geographic profiling: Winthropping. While the method has been around for several decades, few studies have provided any research findings using it. There are two likely reasons for Winthropping being under-used: first, it has not been clearly, theoretically explained; second, given its relative novelty, it may not be immediately clear how to use it in research and real-world scenarios. The current paper outlines several key psychological (e.g., satisficing and affordances) and criminological (e.g., rational choice theory and crime geometry) theories that may explain why Winthropping works. Case studies are provided, and a methodological approach (matrix forecasting) is then provided to show how it could work in research practice and real-world applications. Overall, Winthropping is deemed to be highly useful, and it is hoped that experts in the field will begin developing this tool for wider, applied use. [ABSTRACT FROM AUTHOR]

The important role of student agency in collaborative problem-solving has been acknowledged in previous mathematics education research. However, what remains unknown are the processes of agency in open-ended tasks that draw on real-life contexts and demand argumentation beyond "mathematical". In this study, we analyse a video recording of two student groups (each consisting of four students) taking part in collaborative problem-solving. We draw on the framework for collaborative construction of mathematical arguments and its interplay with student agency by Mueller et al. (2012). This original framework is supplemented by (i) testing and revising it in the context of open-ended real-life tasks, with (ii) student groups rather than pairs working on the tasks, and by (iii) offering a strengthened methodological pathway for analysing student agency in such a context. Based on our findings, we suggest that the framework suits this new context with some extensions. First, we note that differences in student agency were not only identified in terms of the discourse students drew on, but in how students were able to shift between various discourses, such as between "mathematical" and "non-mathematical" discourses. We identify a novel discourse reflecting student agency, invalidation discourse, which refers to denying other students' agency by framing their contribution as invalid. Finally, we discuss the need to reframe "mathematical" arguments—and indeed student agency—while the task at hand is open-ended and concerns real-life contexts. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a leading cause of death and disability among adults. Falls and motor vehicle collisions (MVCs) are the most common causes of TBI hospitalizations in Canada. The purpose of this study was to determine whether, at the provincial level, there have been significant changes in the injury rate and causes of major TBI. This was a retrospective cohort study of all patients in Nova Scotia who presented with major TBI (Abbreviated Injury Scale Head score ≥ 3) between 2002 and 2018. Prospectively entered data were collected from the Nova Scotia Trauma Registry. Annual injury rates were calculated based on 100,000 population (all ages) using population estimates from Statistics Canada. Linear regression was performed to analyze annual trends of major TBI within the province. There were 5590 major TBI patients in Nova Scotia during the 16-year study period. The overall annual rate of major TBI was 37 per 100,000 population. There was a 39% increase in the rate of major TBI over the study period (r = − 0.72, R2 = 0.51, p < 0.002). Patients had a mean age of 51 ± 25 years; 72% were male. The proportion of TBIs in males decreased significantly from 76% in 2002 to 69% in 2017 (p < 0.001). Mechanisms of injury were predominantly falls (45%) and MVCs (29%); the proportion of violent injuries was 11.5%. The rate of fall-related TBIs more than doubled between 2002 and 2017, increasing from 9.1 to 20.5 injuries per 100,000 (p < 0.001). Our findings demonstrate an increasing incidence of major TBI over a 16-year period with a greater than two-fold increase in the rate of fall-related TBI. These results are important for targeting TBI prevention efforts in reducing falls, especially in older adults. [ABSTRACT FROM AUTHOR]

Background/purpose of the study: Little is known about all-cause liver disease in people with serious mental illness (SMI), despite heightened risk factors. We, therefore, prospectively assessed liver disease by etiology and severity in a cross-sectional cohort of people with SMI at a tertiary health service. Methods: We recruited 255 people with SMI between August 2019 and March 2020. Liver disease data were derived from structured interview, medical records, biochemical and BBV serological analyses, and vibration-controlled transient elastography (VCTE). Steatosis was determined using a threshold of ≥ 248 db/m via the controlled attenuation parameter (CAP) on VCTE. Liver disease prevalence was assessed descriptively, and predictors of metabolic-dysfunction associated fatty liver disease (MAFLD) analyzed using linear regression and multivariable analysis. Best fit modeling of non-invasive screening tests for MAFLD was also assessed. Results: Valid VCTE was obtained for 252 (98.9%) participants. Median age was 40 years (IQR 31–49) with male predominance (65.9%). Hepatitis C Virus (HCV) seroprevalence was 14.7% (37/252), with four new viremic cases identified. Hepatic steatosis was diagnosed in 61.5% (155/252) of participants, with MAFLD criteria met in 59.9% (151/252) of cases. Clozapine and paliperidone were associated with hepatic steatosis (CAP + 23.3 db/m, p 0.013 and CAP + 25.5, p 0.037, respectively). Advanced liver disease, defined by LSM ≥ 8.2 kPa, was identified in 26 individuals (10.3%). MAFLD compared to no MAFLD was associated with more advanced liver disease (5.3 kPa, 4.3–6.5 versus 4.9 kPa, 3.9–5.6, p < 0.001). Conclusion: Liver disease is common in people with SMI and should be screened for as part of standard physical health assessment. [ABSTRACT FROM AUTHOR]

Background: Frame registration is a critical step to ensure accurate electrode placement in stereotactic procedures such as stereoelectroencephalography (SEEG) and is routinely done by merging a computed tomography (CT) scan with the preoperative magnetic resonance (MR) examination. Three-dimensional fluoroscopy (XT) has emerged as a method for intraoperative electrode verification following electrode implantation and more recently has been proposed as a registration method with several advantages. Methods: We compared the accuracy of SEEG electrode placement by frame registration with CT and XT imaging by analyzing the Euclidean distance between planned and post-implantation trajectories of the SEEG electrodes to calculate the error in both the entry (EP) and target (TP) points. Other variables included radiation dose, efficiency, and complications. Results: Twenty-seven patients (13 CT and 14 XT) underwent placement of SEEG electrodes (319 in total). The mean EP and TP errors for the CT group were 2.3 mm and 3.3 mm, respectively, and 1.9 mm and 2.9 mm for the XT group, with no statistical difference (p = 0.75 and p = 0.246). The time to first electrode placement was similar (XT, 82 ± 10 min; CT, 84 ± 22 min; p = 0.858) and the average radiation exposure with XT (234 ± 55 mGy*cm) was significantly lower than CT (1245 ± 123 mGy*cm) (p < 0.0001). Four complications were documented with equal incidence in both groups. Conclusions: The use of XT as a method for registration resulted in similar implantation accuracy compared with CT. Advantages of XT are the substantial reduction in radiation dose and the elimination of the need to transfer the patient out of the room which may have an impact on patient safety and OR efficiency. [ABSTRACT FROM AUTHOR]

Purpose: Patients with sellar masses (SM) frequently have secondary hormonal deficiency (SHD) at initial presentation. While larger SM are more likely to present with SHD, it is unclear whether SHD at presentation is influenced by the type of SM. Methods: We conducted a retrospective analysis of patients with SM prospectively enrolled in our comprehensive provincial neuropituitary registry between November 2005 and December 2018. SM were subdivided based on size: < 1 cm, 1–1.9 cm, 2–2.9 cm, and > 3 cm. Results: A total of 914 patients met the inclusion criteria, including: 346 nonfunctioning adenomas (NFA), 261 prolactinomas (PRLoma), 51 growth hormone adenomas, 36 adrenocorticotropic adenomas, 93 Rathke's cleft cysts, 70 craniopharyngiomas and 57 meningiomas. The overall rate of SHD at presentation was highest in PRLoma (62.8%) and craniopharyngiomas (64.3%) and lowest in meningiomas (14%). While larger SM were significantly more likely to have SHD, the rate of SHD within each group was significantly different despite similar size (p < 0.001). Of the two largest groups of SM (NFA and PRLoma), NFA had significantly higher odds ratio (3.34, CI 1.89–5.89) of having multiple SHDs when compare with PRLoma, even when corrected for age, gender and size of tumor (p < 0.001). Conclusion: Our study shows that the rate and distribution of SHD in SM vary dependent upon the size of the tumor and specific pathology; in particular, NFA are more likely to present with multiple SHDs. Our data will help clinicians in determining adequate hormonal testing strategy for different SM. [ABSTRACT FROM AUTHOR]

Coprolites (fossilized faeces) can provide valuable insights into species’ diet and related habits. In archaeozoological contexts, they are a potential source of information on human-animal interactions as well as human and animal subsistence. However, despite a broad discussion on coprolites in archaeology, such finds are rarely subject to detailed examination by researchers, perhaps due to the destructive nature of traditional analytical methods. Here, we have examined coprolitic remains from the Neolithic (third millennium BCE) settlement at Skara Brae, Orkney, using a range of modern methods: X-ray computed tomography, scanning electron microscopy, lipid and protein analysis (shotgun proteomics of the coprolite matrix as well as collagen peptide mass fingerprinting of isolated bone fragments). This combined approach minimised destructiveness of sampling, leaving sufficient material for subsequent study, while providing more information than traditional morphological examination alone. Based on gross visual examination, coprolites were predominantly attributed to domestic dogs (Canis familiaris), with morphologically identified bone inclusions derived from domestic sheep (Ovis aries) and common voles (Microtus arvalis). Partial dissection of a coprolite provided bone samples containing protein markers akin to those of domestic sheep. Considering the predominance of vertebral and distal limb bone fragments, Skara Brae dogs were probably consuming human butchery or meal refuse, either routinely fed to them or scavenged. The presumably opportunistic consumption of rodents may also have played a role in pest control. [ABSTRACT FROM AUTHOR]

When a detective arrives at a crime scene, or investigates multiple cases, they are often tasked with understanding whether the crimes are linked. Knowing whether the same suspect(s) was involved across multiple crimes is a key part of the investigation. To date, there are numerous methods for crime linkage; however, very few take temporal sequences of events into account. It is known that modus operandi and signatures change over time, and therefore, linkage analyses should integrate these temporal changes. The current paper presents a new method of crime linkage, the Path Similarity Metric, which is based on sequence analysis procedures. The method is proposed, outlined, and tested in contrast to existing linkage analyses (e.g., Jaccard's coefficient). The Path Similarity Metric outperforms Jaccard's coefficient across a series of crimes. Future applications of the Path Similarity Metric are outlined, and directions for the use of the metric in ongoing investigations are considered alongside other linkage methods. [ABSTRACT FROM AUTHOR]

The range of the mosquito Aedes aegypti continues to expand, putting more than two billion people at risk of arboviral infection. The sterile insect technique (SIT) has been used to successfully combat agricultural pests at large scale, but not mosquitoes, mainly because of challenges with consistent production and distribution of high-quality male mosquitoes. We describe automated processes to rear and release millions of competitive, sterile male Wolbachia-infected mosquitoes, and use of these males in a large-scale suppression trial in Fresno County, California. In 2018, we released 14.4 million males across three replicate neighborhoods encompassing 293 hectares. At peak mosquito season, the number of female mosquitoes was 95.5% lower (95% CI, 93.6–96.9) in release areas compared to non-release areas, with the most geographically isolated neighborhood reaching a 99% reduction. This work demonstrates the high efficacy of mosquito SIT in an area ninefold larger than in previous similar trials, supporting the potential of this approach in public health and nuisance-mosquito eradication programs. Mosquitoes are nearly eradicated in three suburbs of California using accurately sorted sterile male mosquitoes. [ABSTRACT FROM AUTHOR]

This article examines the mobilization of historical memory as a resource for cultural diplomacy through the medium of the museum. Noting the increasing trend for states to incorporate "dark heritage" of conflict into their cultural diplomacy strategies, the article examines the recent case of the Museum of the Second World War in Gdańsk, which has been heavily criticized by the current Polish government for its alleged failure to convey an adequately heroic account of the war to both domestic and foreign audiences. The article demonstrates that the current Polish government has placed great importance on historical memory as a means of persuading European partners of the validity of its vision of European history and of Poland's place within the contemporary European project. However, in its approach to the Museum of the Second World War, we argue, the Polish government has not developed an effective strategy for mobilizing historical memory to influence others. This case study allows us to demonstrate the potential pitfalls of drawing on historical memory in the context of cultural diplomacy. [ABSTRACT FROM AUTHOR]

Flying insects capable of navigating in highly cluttered natural environments can withstand in-flight collisions because of the combination of their low inertia1 and the resilience of their wings2, exoskeletons1 and muscles. Current insect-scale (less than ten centimetres long and weighing less than five grams) aerial robots3–6 use rigid microscale actuators, which are typically fragile under external impact. Biomimetic artificial muscles7–10 that are capable of large deformation offer a promising alternative for actuation because they can endure the stresses caused by such impacts. However, existing soft actuators11–13 have not yet demonstrated sufficient power density to achieve lift-off, and their actuation nonlinearity and limited bandwidth create further challenges for achieving closed-loop (driven by an input control signal that is adjusted based on sensory feedback) flight control. Here we develop heavier-than-air aerial robots powered by soft artificial muscles that demonstrate open-loop (driven by a predetermined signal without feedback), passively stable (upright during flight) ascending flight as well as closed-loop, hovering flight. The robots are driven by multi-layered dielectric elastomer actuators that weigh 100 milligrams each and have a resonance frequency of 500 hertz and power density of 600 watts per kilogram. To increase the mechanical power output of the actuator and to demonstrate flight control, we present ways to overcome challenges unique to soft actuators, such as nonlinear transduction and dynamic buckling. These robots can sense and withstand collisions with surrounding obstacles and can recover from in-flight collisions by exploiting material robustness and vehicle passive stability. We also fly two micro-aerial vehicles simultaneously in a cluttered environment. They collide with the wall and each other without suffering damage. These robots rely on offboard amplifiers and an external motion-capture system to provide power to the dielectric elastomer actuators and to control their flight. Our work demonstrates how soft actuators can achieve sufficient power density and bandwidth to enable controlled flight, illustrating the potential of developing next-generation agile soft robots. Heavier-than-air insect-scale aerial robots powered by soft artificial muscles can hover and also recover from in-flight collisions, illustrating the potential for developing next-generation agile soft robots. [ABSTRACT FROM AUTHOR]

The benefits of engaging students in mathematics classroom dialogue have been highlighted (and advocated) in a large body of research studies, most of which were conducted in Western cultural contexts. Whether such research advocacy can be extended legitimately to encompass practice in classrooms situated in other cultural contexts, such as East Asian classrooms, remains a matter for empirical investigation. In this paper, we problematize the assumptions underpinning this advocacy of "mathematical dialogue in classrooms" by revisiting several conceptualizations of the role of language in mathematics classrooms and by considering particular forms of communication in classrooms often undervalued in the research literature. To support such problematization, we draw upon an analysis of classroom discourse in nine classrooms situated in Shanghai, Seoul, and Melbourne from the Learner's Perspective Study. The results of the analysis demonstrate some interesting variations in the extent to which the discursive practice of each classroom afforded or constrained the opportunities for students to speak mathematically, and its consequences for student learning as indicated by student mathematical fluency demonstrated in the post-lesson interviews. Such variations provide insight into the differences in inspirations and cultural values attached to particular types of mathematical performance. We argue that our theories should anticipate application in culturally differentiated settings and be sensitive to the constraints and affordance that culture might place on classroom discourse practices. [ABSTRACT FROM AUTHOR]

This study aims to reveal features of student talk over a sequence of consecutive mathematics lessons in a large-size class in mainland China. By examining the time allocation for student talk and the number of Chinese characters spoken by the students, this study finds that, in some of the lessons observed, student talk added up to a longer duration and included a larger number of Chinese characters than teacher talk. But individual students were observed to have unequal opportunities to participate in public talk and there is a large gap regarding the number of Chinese characters that an individual student could speak in public. Each individual student's accountability to talk was recorded to be less diverse in public presentation than in non-presentation contexts (e.g., answering teacher questions). This study suggests that a unit of consecutive lessons can help a clearer and more comprehensive observation and analysis of student talk. [ABSTRACT FROM AUTHOR]

The article focuses on administrations of memory studies, which is a broad convergence field incorporating a range of disciplines in the humanities and social sciences. Other topics being presented include the myriad of case studies produced by researchers in the field which has tended to focus exclusively on memory as a means of fostering the cohesion of the group.

Important contributors to quality of life (QOL), such as psychosocial factors, have received limited exploration in veteran populations, in contrast to a significant amount of research focused on health-related quality of life (HRQL). This study investigated QOL and HRQL amongst Gulf War veterans compared with an era-military comparison group 20 years after the 1990/91 Gulf War, and whether psychiatric status over time and psychiatric comorbidities predicted QOL and HRQL. We then investigated which of a range of psychological health, physical health and social factors contribute greatest to QOL. Psychological interviews and postal questionnaires were administered to a cohort of Gulf War veterans and a military-era comparison group in 2000-02 and 2011-12. Gulf War veterans had poorer QOL and HRQL compared with a military comparison group, but the pattern of factors that influenced QOL was the same for both groups. Poorer QOL and HRQL were significantly associated with more recent and persistent psychiatric morbidity over time. Further analyses showed that affective disorders, followed by anxiety disorders had the largest impact on QOL and HRQL, and that QOL and HRQL were negatively affected by each additional psychiatric diagnosis. The importance of these findings was highlighted in a structural equation model that revealed psychological health contributed most to QOL, social support contributed a moderate amount, but physical health contributed only a very small amount. QOL in veterans is an important issue even many years after deployment and psychological health plays a predominant role in QOL. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to identify psychosocial variables associated with the relationship between weight loss and change in depressive symptoms following gastric banding surgery.Methods: Ninety-nine adults completed self-report questionnaires assessing depressive symptoms and other psychosocial variables (self-esteem, body image dissatisfaction, perceived physical health, and perceived weight-based stigmatisation) prior to gastric-band surgery and monthly for 6-month post-surgery.Results: Weight, depressive symptoms, and other psychosocial variables improved significantly 1-month post-surgery and remained lower to 6 months. Weight loss from baseline to 1- and 6-months post-surgery significantly correlated with change in depressive symptoms. Body image dissatisfaction and self-esteem accounted for some of the variance in change in depressive symptoms from baseline to 1-month and baseline to 6-months post-surgery.Conclusions: Depressive symptoms improved significantly and rapidly after bariatric surgery, and body image dissatisfaction and self-esteem predicted change in depressive symptoms. Interventions targeting body image and self-esteem may improve depressive symptoms for those undergoing weight loss interventions. [ABSTRACT FROM AUTHOR]

Purpose: This report describes the views of front-line health professionals who participated in a randomised controlled trial examining a model of care in which depressed cancer patients received a brief psychosocial intervention. Health professionals from four cancer centres received focused training, skill development and clinical supervision in order to deliver the intervention.Methods: We interviewed 20 health professionals asking them about their perceptions of participation in the study and their views about more widespread implementation of this model of care.Results: Participants strongly advocated for widespread implementation of this model of care; however, their ability to deliver the intervention varied depending on clinical roles and responsibilities. Many oncology nurses expressed conflict about delivering a psychosocial intervention when their clinical unit was busy. Finding a private area in which to talk was a frequent barrier in busy clinical units. Participants reported that they applied the skills and insights acquired in the study in their routine clinical work. Supervision was highly valued and was feasible to provide in clinical settings.Conclusion: Psychosocial care can be provided by a range of health professionals if they receive focused training and have access to supervision, but competing clinical demands are likely to limit their ability to routinely provide psychosocial care. This suggests that training should target professionals who have greater autonomy and flexibility in their work roles.Trial Registration Number: ANZCTR1260000448044. [ABSTRACT FROM AUTHOR]

The major premise of this project is that teachers learn from the act of teaching a lesson. Rather than asking “What must a teacher already know in order to practice effectively?”, this project asks “What might a teacher learn through their activities in the classroom and how might this learning be optimised?” In this project, controlled conditions are created utilising purposefully designed and trialled lesson plans to investigate the process of teacher knowledge construction, with teacher selective attention proposed as a key mediating variable. In order to investigate teacher learning through classroom practice, the project addresses the following questions: To what classroom objects, actions and events do teachers attend and with what consequence for their learning? Do teachers in different countries attend to different classroom events and consequently derive different learning benefits from teaching a lesson? This international project combines focused case studies with an online survey of mathematics teachers’ selective attention and consequent learning in Australia, China and Germany. Data include the teacher’s adaptation of a pre-designed lesson, the teacher’s actions during the lesson, the teacher’s reflective thoughts about the lesson and, most importantly, the consequences for the planning and delivery of a second lesson. The combination of fine-grained, culturally situated case studies and large-scale online survey provides mutually informing benefits from each research approach. The research design, so constituted, offers the means to a new and scalable vision of teacher learning and its promotion. [ABSTRACT FROM AUTHOR]

Interactive problem solving and learning are priorities in contemporary education, but these complex processes have proved difficult to research. This project addresses the question “How do we optimise social interaction for the promotion of learning in a mathematics classroom?” Employing the logic of multi-theoretic research design, this project uses the newly built Science of Learning Research Classroom (ARC-SR120300015) at The University of Melbourne and equivalent facilities in China to investigate classroom learning and social interactions, focusing on collaborative small group problem solving as a way to make the social aspects of learning visible. In Australia and China, intact classes of local year 7 students with their usual teacher will be brought into the research classroom facilities with built-in video cameras and audio recording equipment to participate in purposefully designed activities in mathematics. The students will undertake a sequence of tasks in the social units of individual, pair, small group (typically four students) and whole class. The conditions for student collaborative problem solving and learning will be manipulated so that student and teacher contributions to that learning process can be distinguished. Parallel and comparative analyses will identify culture-specific interactive patterns and provide the basis for hypotheses about the learning characteristics underlying collaborative problem solving performance documented in the research classrooms in each country. The ultimate goals of the project are to generate, develop and test more sophisticated hypotheses for the optimisation of social interaction in the mathematics classroom in the interest of improving learning and, particularly, student collaborative problem solving. [ABSTRACT FROM AUTHOR]

Contemporary curriculum demands the development of both problem solving skills and negotiative skills required for collaborative group work. Tasks are required that create the best possible conditions for students to develop both of these skill sets. Open-ended tasks have been shown to provide these conditions, but they also require the teacher to relinquish some level of control over student activity, since the open-endedness of the tasks provides students with the opportunity to realize their intentions rather than just the teacher's. It is necessary to investigate the nature of the affordances created by the use of open-ended tasks in order to anticipate how they might best be used for both instruction and learning. What is needed is a structured way to identify the affordances offered by open-ended tasks. This paper reports a study conducted in a laboratory classroom equipped to record classroom social interactions in great detail using advanced video technology. The reported analysis addresses the following question: What are the foci of the students' social interactions during collaborative problem solving while attempting open-ended mathematical tasks? Analysis was carried out in relation to each type of data generated: written response, transcripts and videos. Our research has identified structures to represent these affordances so that teachers can both anticipate them and draw on them in monitoring and facilitating student collaborative problem solving. The structured identification of affordances in relation to (a) written product and (b) negotiative focus provides teachers with two frameworks by which to scaffold student collaborative work while attempting open-ended tasks. [ABSTRACT FROM AUTHOR]

Stimulating thinking related to mathematical content is the focus of many tasks in the mathematics classroom. Beyond such content-related thinking, promoting forms of higher order thinking is among the goals of mathematics instruction as well. So-called hybrid tasks focus on combining both goals: they aim at fostering mathematical thinking and higher order thinking through the same mathematical activities-an aim which requires empirical examination. For empirically valid hybrid task design, evidence is required about the nature of the interrelatedness of content-related and higher order thinking. In this article, we choose the example of statistical thinking and critical thinking for exploring the interrelatedness of these different modes of thinking when solving hybrid tasks. Even if theories about statistical thinking and critical thinking have so far followed almost separate strands, there are commonalities at the theoretical level, which facilitate hybrid task design. We report an empirical study, in which a bottom-up analysis of thinking-aloud interviews with adult learners around solution processes of hybrid tasks affords insight into how these modes of thinking may interact when solving such tasks. The results show that the tasks did evoke both statistical thinking and critical thinking: Both modes of thinking entered in an interplay in which we observed instances of mutual support of both modes of thinking, but also cases in which a strong focus on statistical thinking or critical thinking appeared to impede the other mode of thinking, respectively. The findings can inform the further development of hybrid tasks: Based on the observations, the task format can be enriched with specific reflective stimuli intended to support a fruitful interplay of statistical thinking and critical thinking. [ABSTRACT FROM AUTHOR]

We articulate a student perspective on task design in mathematics education, foregrounding a dynamic relationship between intentions of task designers, teachers, and students. First, we characterize a student perspective on task design. Second, we provide theoretical perspectives that we use as tools to account for different facets of task design from a student perspective. Third, we elaborate on 'tensions of intentions' between designers, teachers, and students when considering the use of tasks to promote students' mathematical learning. Fourth, we address mathematical tasks and the student: characterizing task context from a student perspective, contrasting reflective and emergent task design, and discussing theoretical and methodological approaches that take into account the student perspective. We conclude with implications for research and practice. [ABSTRACT FROM AUTHOR]

The contribution of the gut microbiota to the metabolism of cholesterol is not well understood. In this study, we identify 21 fosmid clones from a human gut microbiome metagenomic library that, when expressed in Escherichia coli, produce halos on LB agar supplemented with 0.01% (w/v) cholesterol (LBC agar). Analysis of 14 of these clones revealed that they all share a fragment of DNA with homology to the genome of Bacteroides vulgatus. The gene responsible for halo production on LBC agar, named choA, was identified as an N-acyltransferase known to produce an acylated glycine molecule called commendamide. In this study we show that commendamide is capable of producing a halo on LBC agar suggesting that this molecule is solubilizing the cholesterol micelles in LBC agar. We also show that commendamide is responsible for the previously described hemolytic activity associated with the choA orthologue in Bacteroides fragilis. A functional analysis of ChoA identified 2 amino acids that are important for commendamide biosynthesis and we present phylogenetic and functional data showing that orthologues of choA are found only in the order Bacteroidales. Therefore, the production of commendamide may be an adaptation to the environments colonized by the Bacteroidales, including the mammalian gut. [ABSTRACT FROM AUTHOR]

This article describes the research landscape related to the use of video for promoting teacher learning, drawing on a variety of research studies to illustrate the breadth of approaches that have been employed. One particular research study is reported in some detail since, it is argued, this represents a new level of devolution of agency to teachers to play a self-scaffolding role in their own professional education. The study involved the investigation of an approach to the provision of feedback to teachers about their practice that involved stimulating teacher self-reflection and juxtaposed structure and agency. An observation framework grounded in classroom practice research was developed, and teachers selected elements of that framework to serve as the focus for examining their practice and seeking feedback about that practice. Teachers and researchers examined video-recorded lessons focusing on the teachers' selected observation elements, and then engaged in feedback conversations about their observations and analyses, and the implications of these for future practice. The approach identified the video record as an artefact of the teacher's own practice and one which demanded a professional response from the teacher. The balance between structure and agency realised in the study, in combination with the use of video for observation and analysis of practice, facilitated teacher self-reflection and functioned to both support and provoke teacher learning. [ABSTRACT FROM AUTHOR]

Intranasally administered regular insulin and insulin aspart have shown cognitive benefit for patients with Alzheimer's disease (AD). To support development of intranasally administered insulin analogs for AD, the central disposition of intranasal insulin lispro in the cerebrospinal fluid (CSF) of healthy volunteers was investigated. Healthy volunteers ( N = 8) received two sequential doses of intranasal insulin lispro (48 or 80 IU followed by 160 IU) by Aero Pump in an open-label, single-period study with serial CSF and serum sampling over 5 hours after each dose. CSF insulin lispro was also measured in beagle dogs ( N = 6/dose group) that received either 24 IU/kg (equivalent local nasal (IU/cm) dose to the human 160 IU dose) or 192 IU/kg intranasally, using the same device. Insulin lispro was measured in the CSF and serum using a validated enzyme-linked immunosorbent assay method, and pharmacokinetic parameters were calculated by standard noncompartmental methods. Intranasal administration of insulin lispro was well tolerated. Insulin lispro concentrations in the CSF of humans at all dose levels were below the limit of quantification. Serum insulin lispro concentrations were quantifiable only up to 1-2 hours in the majority of subjects. In contrast to insulin lispro in the CSF of humans, insulin lispro was detectable in the CSF at both dose levels in dogs, and serum concentrations of insulin lispro were generally higher in dogs than in healthy volunteers. The absence of insulin lispro in CSF from healthy volunteers and the lack of robust exposure-response analyses will hinder the development of intranasally administered insulin lispro for AD. [ABSTRACT FROM AUTHOR]

Bicycle-related injuries are a leading cause of child and youth hospitalizations in Canada. The use of helmets while bicycling reduces the risk of brain injuries. This study investigated the long-term effect of legislation coupled with enforcement to improve helmet use rates. We conducted a longitudinal observational study of helmet use at 9, 11, and 14 years after bicycle helmet legislation was enacted. Data were compared to baseline observations collected after legislation was passed in 1997. A comprehensive enforcement and educational diversion program, Operation Headway-Noggin Knowledge (OP-NK), was developed and implemented in partnership with regional police during the study period. Helmet use was sustained throughout the post-legislation period, from 75.3 % in the year legislation was enacted to 94.2 % 14 years post-legislation. The increase in helmet use was seen among all age groups and genders. Helmet legislation was not associated with changes in bicycle ridership over the study years. OP-NK was associated with improved enforcement efforts as evidenced by the number of tickets issued to noncompliant bicycle riders. This observational study spans a 16-year study period extending from pre-legislation to 14 years post all-age bicycle helmet legislation. Our study results demonstrate that a comprehensive approach that couples education and awareness with ongoing enforcement of helmet legislation is associated with long-term sustained helmet use rates. The diversion program described herein is listed among best practices by the Public Health Agency of Canada. [ABSTRACT FROM AUTHOR]

Purpose: A stepped-wedge cluster-randomised controlled trial was conducted to evaluate the feasibility and effectiveness of a brief psychosocial intervention for depressed cancer patients, delivered by trained front-line health professionals in routine clinical care.Methods: Nine hundred two patients were assessed across four treatment centres which were allocated in random order from control epoch to intervention epoch. Eligible patients had Hospital Anxiety and Depression Scale (HADS) scores of 8 or greater. Of eligible patients, 222 were recruited in control epoch and 247 in intervention epoch. Twenty-seven health professionals (HPs) were trained to deliver the psychosocial intervention consisting of up to four sessions, tailored to patient symptoms and distress. HPs participated in group supervision with a psychiatrist. The primary outcome, analysed by intention to treat, was depression measured with the HADS at 10 weeks after receiving the intervention.Results: At 10-week follow-up, there were no significant differences in HADS score for the 181 patients in control epoch and 177 in intervention epoch (adjusted difference -1.23, 95 % CI -3.81--1.35, p = 0.35). Patients with disease progression who received the intervention experienced significant benefits in unmet practical support needs including care and support, information, and physical and daily living.Conclusion: A brief psychosocial intervention delivered by front-line oncology health professionals is feasible to deliver but is insufficient as a stand-alone treatment for depression in cancer patients. Psychosocial interventions should be targeted to populations most likely to experience benefit. [ABSTRACT FROM AUTHOR]

Antimalarial drugs have thus far been chiefly derived from two sources--natural products and synthetic drug-like compounds. Here we investigate whether antimalarial agents with novel mechanisms of action could be discovered using a diverse collection of synthetic compounds that have three-dimensional features reminiscent of natural products and are underrepresented in typical screening collections. We report the identification of such compounds with both previously reported and undescribed mechanisms of action, including a series of bicyclic azetidines that inhibit a new antimalarial target, phenylalanyl-tRNA synthetase. These molecules are curative in mice at a single, low dose and show activity against all parasite life stages in multiple in vivo efficacy models. Our findings identify bicyclic azetidines with the potential to both cure and prevent transmission of the disease as well as protect at-risk populations with a single oral dose, highlighting the strength of diversity-oriented synthesis in revealing promising therapeutic targets. [ABSTRACT FROM AUTHOR]

Purpose: Understanding how veterans appraise their post-deployment experiences could provide insight into better assisting their deployment transitions. We aimed to assess the factor structure of positive and negative post-deployment appraisals in Australian veterans and to examine the resultant factors in their relationship with military stress and psychological health.Method: Questions capturing post-deployment attitudes were developed by the researchers in collaboration with veterans. The questions were administered to 1938 veterans and the results factor analysed. The relationships between post-deployment appraisal, military stress and psychological health were examined using Structural Equation Modelling.Results: A three-factor solution was found for the post-deployment appraisal questions; representing personal development, lack of recognition, and appreciation of life and country. Military stress was associated with the three factors and psychological health. The three factors were weakly to moderately associated with psychological health. Mediation between military stress and psychological health by any post-deployment appraisal factor was minimal.Conclusions: Post-deployment appraisal measures three important attitudes and concerns of veterans after deployment. Military stress is associated with the post-deployment appraisal factors. However, the factors did not mediate the relationship between military stress and psychological health. These factors provide insight into how veterans appraise their complex array of post-deployment experiences, and may provide useful in regard to transitions and integration into civilian life. [ABSTRACT FROM AUTHOR]

Fritz Lang's (1927) Metropolis has been subject to innumerable would-be allegorical interpretations. The present paper offers an analysis of the film's structure in relation to Lévi-Strauss's account of myth, where myth provides an imaginary solution to a real contradiction. Adopting a formalist approach, the paper avoids viewing the film as a simple reflection of Weimar culture or anticipation of a National Socialist future, allowing an assessment of the antimonies the narrative negotiates to steer the analysis. The film's ostensibly central contradiction-defined in terms of class conflict and its mediation-is taken as a point of departure, considering the role of the 'heart' in mediating between the 'head' and the 'hands' in terms of a gendered discourse centred on the opposition between nature (figured as feminine) and culture (masculine). This is pursued in relation to technology and artificial life; the film's psychoanalytic resonances; and the religious overtones accompanying its Oedipal aspect. Addressing the film's problematization of the Oedipal narrative arising from the absent mother, the paper highlights Metropolis's previously unacknowledged debt to the Parsifal myth, characterized by Lévi-Strauss as an 'inverse Oedipus'. The film's double structure, superimposing elements of Oedipus and Parsifal, sheds light on its ambivalent reception, which-as the product of one of the most creative and convulsive periods of twentieth-century history-is framed in terms of the distinction between neurosis and psychosis. Having focused squarely on the film's mythical dimension, the paper closes with the possibility of an 'Anti-Oedipal' reading and points towards a fuller allegorical interpretation. [ABSTRACT FROM AUTHOR]