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Abstract Metal-organic frameworks (MOFs) are currently widely investigated for a number of potential biomedicinal applications, with particular focus on nanoscale drug delivery. Nanomedicine in general comes with specific challenges to ensure reproducibility of results, including batch-to-batch variations in ostensibly the same nanomaterial, differences in synthetic and analytical practices, intrinsic issues with in vitro culturing and assaying, and a lack of availability of raw data for comparative analysis. This perspective provides an overview of reproducibility issues in the context of MOFs in nanomedicine, covering their preparation and in vitro analysis. The commonly studied UiO-66 is used as an exemplar to highlight variability in synthetic and characterisation practices, as well as in the publication and availability of data. Some common roadblocks to reproducibility are highlighted, alongside suggestions and resources for best practice.

ABSTRACTWhat cultural ecosystem services (CES) do people perceive in their immediate surroundings, and what sensory experiences are linked to these ecosystem services? And how are these CES and experiences expressed in natural language? In this study, we used data generated through a gamified application called Window Expeditions, where people uploaded short descriptions of landscapes they were able to experience through their windows during the COVID-19 pandemic. We used a combination of annotation, close reading and distant reading using natural language processing and graph analysis to extract CES and sensory experiences and link these to biophysical landscape elements. In total, 272 users contributed 373 descriptions in English across more than 40 countries. Of the cultural ecosystem services, recreation was the most prominently described, followed by heritage, identity and tranquility. Descriptions of sensory experiences focused on the visual but also included auditory experiences and touch and feel. Sensory experiences and cultural ecosystem services varied according to biophysical landscape elements, with, for example, animals being more associated with sound and touch/feel and heritage being more associated with moving objects and the built environment. Sentiments also varied across the senses, with the visual being more strongly associated with positive experiences than other senses. This study showed how a hybrid approach combining manual analysis and natural language processing can be productively applied to landscape descriptions generated by members of the public, and how CES on everyday lived landscapes can be extracted from such data sources.

ABSTRACT The two species that account for most cases of Acinetobacter-associated bacteremia in the United Kingdom are Acinetobacter lwoffii, often a commensal but also an emerging pathogen, and Acinetobacter baumannii, a well-known antibiotic-resistant species. While these species both cause similar types of human infection and occupy the same niche, A. lwoffii (unlike A. baumannii) has thus far remained susceptible to antibiotics. Comparatively little is known about the biology of A. lwoffii, and this is the largest study on it conducted to date, providing valuable insights into its behaviour and potential threat to human health. This study aimed to explain the antibiotic susceptibility, virulence, and fundamental biological differences between these two species. The relative susceptibility of A. lwoffii was explained as it encoded fewer antibiotic resistance and efflux pump genes than A. baumannii (9 and 30, respectively). While both species had markers of horizontal gene transfer, A. lwoffii encoded more DNA defense systems and harbored a far more restricted range of plasmids. Furthermore, A. lwoffii displayed a reduced ability to select for antibiotic resistance mutations, form biofilm, and infect both in vivo and in in vitro models of infection. This study suggests that the emerging pathogen A. lwoffii has remained susceptible to antibiotics because mechanisms exist to make it highly selective about the DNA it acquires, and we hypothesize that the fact that it only harbors a single RND system restricts the ability to select for resistance mutations. This provides valuable insights into how development of resistance can be constrained in Gram-negative bacteria.IMPORTANCEAcinetobacter lwoffii is often a harmless commensal but is also an emerging pathogen and is the most common cause of Acinetobacter-derived bloodstream infections in England and Wales. In contrast to the well-studied and often highly drug-resistant A. baumannii, A. lwoffii has remained susceptible to antibiotics. This study explains why this organism has not evolved resistance to antibiotics. These new insights are important to understand why and how some species develop antibiotic resistance, while others do not, and could inform future novel treatment strategies.

City Walking Tour Videos (CWTVs) are a novel source of Volunteered Geographic Information providing street-level imagery through video sharing platforms such as YouTube. We demonstrate that these videos contain rich information for urban analytical applications, by conducting a mobility study. We detect transport modes with a focus on active (pedestrians and cyclists) and motorised mobility (cars, motorcyclists and trucks). We chose the City of Paris as our area of interest given the rapid expansion of the bicycle network as a response to the Covid-19 pandemic and compiled a video corpus encompassing more than 66 hours of video footage. Through the detection of street names in the video and placename containing timestamps we extracted and georeferenced 1169 locations at which we summarise the detected transport modes. Our results show high potential of CWTVs for studying urban mobility applications. We detected significant shifts in the mobility mix before and during the pandemic as well as weather effects on the volumes of pedestrians and cyclists. Combined with the observed increase in data availability over the years we suggest that CWTVs have considerable potential for other applications in the field of urban analytics.

Blastocystis is a genus of intestinal stramenopiles that infect vertebrates, and may cause disease of the alimentary tract. Currently, at least 40 genotypes (“subtypes”) of Blastocystis are recognised worldwide based on sequence data for the small subunit of the nuclear ribosomal RNA (SSU-rRNA) gene. Despite the numerous studies of Blastocystis worldwide, very few studies have explored Blastocystis in wild animals, particularly in Australia. Here, we used a PCR-based next generation sequencing (NGS)–phylogenetic approach to genetically characterise and classify Blastocystis variants from selected wildlife in the Australian state of Victoria. In total, 1658 faecal samples were collected from nine host species, including eastern grey kangaroo, swamp wallaby, common wombat, deer, European rabbit, canines and emu. Genomic DNA was extracted from these samples, a 500 bp region of the SSU-rRNA gene amplified by polymerase chain reaction (PCR) and, then, a subset of samples sequenced using Illumina technology. Primary PCR detected Blastocystis in 482 of the 1658 samples (29%), with the highest percentage in fallow deer (63%). Subsequent, Illumina-based sequencing of a subset of 356 samples revealed 55 distinct amplicon sequence variants (ASVs) representing seven currently-recognised subtypes (STs) [ST13 (prominent in marsupials), ST10, ST14, ST21, ST23, ST24 and ST25 (prominent in deer)] and two novel STs (ST45 and ST46) in marsupials. Mixed infections of different STs were observed in macropods, deer, emu and canids (fox, feral dog or dingo), but no infection was detected in rabbits or wombats. This study reveals marked genetic diversity within Blastocystis in a small number of species of wild animals in Australia, suggesting complexity in the genetic composition and transmission patterns of members of the genus Blastocystis in this country.

The applicability of electrical impedance tomography (EIT) in birds is unknown. This study aimed to evaluate the use of EIT in anaesthetised chickens in four recumbency positions. Four adult Hyline chickens were anaesthetised with isoflurane in oxygen, and intubated endotracheally for computed tomography (CT). A rubber belt was placed around the coelom caudal to the shoulder joint. A chicken-specific finite element (FE) model, which is essential to generate anatomically accurate functional EIT images for analysis, was constructed based on the CT images obtained at the belt level. Ten additional chickens were anaesthetised with the same protocol. An EIT electrode belt was placed at the same location. The chickens were breathing spontaneously and positioned in dorsal, ventral, right and left lateral recumbency in a randomised order. For each recumbency, raw EIT data were collected over 2 min after 13 min of stabilisation. The data were reconstructed into functional EIT images. EIT variables including tidal impedance variation (TIV), centre of ventilation right to left (CoVRL) and ventral to dorsal (CoVVD), right to left (RL) ratio, impedance change (ΔZ) and eight regional impedance changes including the dorsal, central-dorsal, central-ventral and ventral regions of the right and left regions were analysed. Four breathing patterns (BrP) were observed and categorised based on the expiratory curve. A linear mixed model was used to compare EIT variables between recumbencies. Fisher's exact test was used to compare the frequencies of breathing patterns for each recumbency. The ΔZ observed was synchronous to ventilation, and represented tidal volume of the cranial air sacs as confirmed by CT. Significant differences were found in CoVVD and regional impedance changes between dorsal and ventral recumbencies (P < 0.05), and in CoVRL, RL ratio and regional impedance changes between right and left recumbencies (P < 0.05), which suggested a tendency for the distribution of ventilation to shift towards non-dependent air sacs. No differences were found for TIV and respiratory rate between recumbencies. Recumbency had a significant effect on the frequencies of each of the four BrPs (P = 0.001). EIT can monitor the magnitude and distribution of ventilation of the cranial air sacs in different recumbencies in anaesthetised chickens.

Studies assessing animal pain in veterinary research are often performed primarily for the benefit of animals. Frequently, the goal of these studies is to determine whether the analgesic effect of a novel treatment is clinically meaningful, and therefore has the capacity to improve the welfare of treated animals. To determine the treatment effect of a potential analgesic, control groups are necessary to allow comparison. There are negative control groups (where pain is unattenuated) and positive control groups (where pain is attenuated). Arising out of animal welfare concerns, there is growing reluctance to use negative control groups in pain studies. But for studies where pain is experimentally induced, the absence of a negative control group removes the opportunity to demonstrate that the study methods could differentiate a positive control intervention from doing nothing at all. For studies that are controlled by a single comparison group, the capacity to distinguish treatment effects from experimental noise is more difficult; especially considering that pain studies often involve small sample sizes, small and variable treatment effects, systematic error and use pain assessment measures that are unreliable. Due to these limitations, and with a focus on farm animals, we argue that many pain studies would be enhanced by the simultaneous inclusion of positive and negative control groups. This would help provide study-specific definitions of pain and pain attenuation, thereby permitting more reliable estimates of treatment effects. Adoption of our suggested refinements could improve animal welfare outcomes for millions of animals globally.

Abstract Background Frailty is prevalent in older people with chronic kidney disease (CKD) and robust evidence supporting the benefit of dialysis in this setting is lacking. We aimed to measure frailty and quality of life (QOL) longitudinally in older people with advanced CKD and assess the impact of dialysis initiation on frailty, QOL and mortality. Methods Outpatients aged ≥65 with an eGFR ≤ 20ml/minute/1.73m2 were enrolled in a prospective observational study and followed up four years later. Frailty status was measured using a Frailty Index (FI), and QOL was evaluated using the EuroQol 5D-5L instrument. Mortality and dialysis status were determined through inspection of electronic records. Results Ninety-eight participants were enrolled. Between enrolment and follow-up, 36% of participants commenced dialysis and 59% died. Frailty prevalence increased from 47% at baseline to 86% at follow-up (change in median FI = 0.22, p

The use of bicycles can provide myriad benefits to society, especially in crowded urban centres where other modes of transport are at or near capacity. However, integrating cycling into policy and planning requires more comprehensive data about their use in space and time. Current approaches, using sparse networks of counters provide one possible route to more comprehensive data. In this paper we investigate another, using data collected from Paris’ bicycle sharing system to explore use during 2020. We chose 2020 as a test year because the use of bicycles was strongly influenced by the COVID-19 pandemic, allowing us to explore how bicycle use adapted to both legal and environmental influences. We used interactive visualization to allow hypothesis generation and data exploration, before analysing bicycle use as a function of weather and COVID-19 restrictions. Our results show that bicycle sharing system data and Paris’ counters both capture very similar behaviour patterns, and therefore bicycle sharing system data are a reliable proxy for overall cycling behaviour, providing finer spatial granularity than existing sparse counter networks. Seasonally, precipitation influenced bicycle use more strongly in 2020 than COVID-19 measures.

Background. Clinical Practice Guidelines suggest that frailty be measured during kidney transplant eligibility assessments. Yet it is not known how frailty is best assessed in this setting or whether its assessment is acceptable to patients. We aimed to examine the construct validity and feasibility of Frailty Index (FI) assessment among patients attending a kidney transplant assessment clinic and to explore patients’ perspectives on frailty and the acceptability of its routine assessment. Methods. A 58-item FI was calculated for 147 clinic patients. Semistructured interviews were conducted with a subgroup of 29 patients. The FI was validated against normative FI characteristics (mean, distribution, limit), age, and the Estimated Post-Transplant Survival Score. Feasibility was assessed using descriptive statistics. Qualitative data were analyzed using reflexive thematic analysis. Results. The mean FI was 0.23 (±0.10, normal distribution, limit 0.53). FI increased with age and Estimated Post-Transplant Survival score. The FI was completed for 62.8% of eligible patients (147/234). The median completion time was 10 min, and completion rate (with no missing data) was 100%. Four themes were identified: perceptions of frailty, acceptability, perceived benefits, and risks of frailty measurement. Patients linked frailty with age and adverse outcomes, and most did not consider themselves frail. Patients reported that the FI was quick, simple, and efficient. They felt that frailty assessment is relevant to transplant eligibility and should be used to address potentially reversible factors. Conclusions. The FI demonstrated construct validity and was feasible and acceptable in this clinic setting. The challenge is ensuring that routine assessments lead to better care.

Abstract Background Modulating the microbiota in the large intestine of kidney transplant recipients through prebiotic supplementation may prevent infectious complications from occurring. To date, there have been no interventional trials which have investigated this novel treatment in kidney transplantation. The aim of PREBIOTIC is to assess the feasibility of performing a randomised controlled trial of prebiotics in reducing infections and gastrointestinal symptoms in kidney transplant recipients. Methods Sixty kidney transplant patients will be recruited to a double-blind, placebo-controlled, randomised feasibility trial. Patients will be provided with prebiotic therapy or placebo for 4 to 6 weeks. Outcomes will include recruitment, adherence, tolerance, retention, laboratory parameters (including serum indoxyl sulphate, ρ-cresyl sulphate and stool collection), patients’ self-assessed quality of life, gastrointestinal symptoms and clinical outcomes. Discussion This trial will assess the feasibility of prebiotic supplementation in kidney transplant recipients. Prebiotics not only may alter the gut microbiota and their inherent metabolism and production of uraemic toxins but also may prevent infections from occurring in kidney transplant recipients. Trial registration Australian New Zealand Clinical Trials Registry number ACTRN12618001057279p. The date of registration was 25th June 2018, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375370&isReview=true .

We report on the design, production, and performance of compact 40-cm3 Time Projection Chambers (TPCs) that detect fast neutrons by measuring the three-dimensional (3D) ionization distribution of nuclear recoils in 4He:CO2 gas at atmospheric pressure. We use these detectors to characterize the fast-neutron flux inside the Belle II detector at the SuperKEKB electron–positron collider in Tsukuba, Japan, where the primary design constraint is a small form factor. We find that the TPCs meet or exceed all design specifications, and are capable of measuring the 3D surface shape and charge density profile of ionization clouds from nuclear recoils and charged tracks in exquisite detail. Scaled-up detectors based on the detection principle demonstrated here may be suitable for directional dark matter searches, measurements of coherent neutrino–nucleus scattering, and other experiments requiring precise detection of neutrons or nuclear recoils.

Abstract Objective There are few multinational studies on gestational trophoblastic neoplasia (GTN) treatment outcomes in South America. The purpose of this study was to assess the clinical presentation, treatment outcomes, and factors associated with chemoresistance in low-risk postmolar GTN treated with first-line single-agent chemotherapy in three South American centers. Methods Multicentric, historical cohort study including women with International Federation of Gynecology and Obstetrics (FIGO)-staged low-risk postmolar GTN attending centers in Argentina, Brazil, and Colombia between 1990 and 2014. Data were obtained on patient characteristics, disease presentation, and treatment response. Logistic regression was used to assess the relationship between clinical factors and resistance to first-line single-agent treatment. A multivariate analysis of the clinical factors significant in univariate analysis was performed. Results A total of 163 women with low-risk GTN were included in the analysis. The overall rate of complete response to first-line chemotherapy was 80% (130/163). The rates of complete response to methotrexate or actinomycin-D as first-line treatment, and actinomycin-D as second-line treatment postmethotrexate failure were 79% (125/157), 83% (⅚), and 70% (23/33), respectively. Switching to second-line treatment due to chemoresistance occurred in 20.2% of cases (33/163). The multivariate analysis demonstrated that patients with a 5 to 6 FIGO risk score were 4.2-fold more likely to develop resistance to first-line single-agent treatment (p= 0.019). Conclusion 1) At presentation, most women showed clinical characteristics favorable to a good outcome, 2) the overall rate of sustained complete remission after first-line single-agent treatment was comparable to that observed in developed countries, 3) a FIGO risk score of 5 or 6 is associated with development of resistance to first-line single-agent chemotherapy.

Androgen deprivation therapy is a cornerstone of treatment for advanced prostate cancer, and the development of castrate-resistant prostate cancer (CRPC) is the primary cause of prostate cancer-related mortality. While CRPC typically develops through a gain in androgen receptor (AR) signaling, a subset of CRPC will lose reliance on the AR. This process involves genetic, epigenetic, and hormonal changes that promote cellular plasticity, leading to AR-indifferent disease, with neuroendocrine prostate cancer (NEPC) being the quintessential example. NEPC is enriched following treatment with second-generation anti-androgens and exhibits resistance to endocrine therapy. Loss of RB1, TP53, and PTEN expression and MYCN and AURKA amplification appear to be key drivers for NEPC differentiation. Epigenetic modifications also play an important role in the transition to a neuroendocrine phenotype. DNA methylation of specific gene promoters can regulate lineage commitment and differentiation. Histone methylation can suppress AR expression and promote neuroendocrine-specific gene expression. Emerging data suggest that EZH2 is a key regulator of this epigenetic rewiring. Several mechanisms drive AR-dependent castration resistance, notably AR splice variant expression, expression of the adrenal-permissive 3βHSD1 allele, and glucocorticoid receptor expression. Aberrant epigenetic regulation also promotes radioresistance by altering the expression of DNA repair- and cell cycle-related genes. Novel therapies are currently being developed to target these diverse genetic, epigenetic, and hormonal mechanisms promoting lineage plasticity-driven NEPC.

Data regarding dermatology residency interview patterns can better inform applicants regarding the application process as well as encourage further coordination among programs. Our objective was to describe dermatology residency interview date patterns over the past five applications cycles from 2012 to 2017. A retrospective review of dermatology online forums (the Dermatology Interest Group Association and Student Doctor Network) was performed from 2012 to 2017; these web-based public databases were reviewed for interview dates and interview offer dates. Data from 117 programs per year were obtained. The majority of interview offers arrived in early November (41.5%), followed by late November (40%). Interviews were conducted predominantly in December (25.7%) and January (66.3%). On average, programs scheduled 2.26 (range 1-13) interview dates. Most interviews were held on Thursday (23.9%) and Friday (28.7%). Our results suggest that there is an increasing trend of overlapping interview dates among programs. Being cognizant of dermatology residency interview date patterns can help prepare applicants for interview scheduling while avoiding scheduling conflicts.

Studies of human spatial behavior increasingly rely on a combination of audiovisual and geospatial recordings. So far, however, few analytical environments have offered opportunities for integrated and expedient annotation and analysis of the two. Here we report the first study aimed at integrating geospatial data in an environment developed for time-aligned annotation of audiovisual media. By calibrating the audiovisual and geospatial signals on the timeline and inserting the geo data as a tier in the annotation tool ELAN, we innovatively generate an environment in which time-aligned annotations of audiovisually observed behavior can be linked and explored in relation to the corresponding geographical coordinates. We illustrate the technique with cultural and linguistic behavior recorded on the move among indigenous communities in Southeast Asia. Our methodological principle is of potential interest to any study or discipline concerned with linking the location and properties of observable behavior.

Events profoundly influence human-environment interactions. Through repetition, some events manifest and amplify collective behavioral traits, which significantly affects landscapes and their use, meaning, and value. However, the majority of research on reaction to events focuses on case studies, based on spatial subsets of data. This makes it difficult to put observations into context and to isolate sources of noise or bias found in data. As a result, inclusion of perceived aesthetic values, for example, in cultural ecosystem services, as a means to protect and develop landscapes, remains problematic. In this work, we focus on human behavior worldwide by exploring global reactions to sunset and sunrise using two datasets collected from Instagram and Flickr. By focusing on the consistency and reproducibility of results across these datasets, our goal is to contribute to the development of more robust methods for identifying landscape preference using geo-social media data, while also exploring motivations for photographing these particular events. Based on a four facet context model, reactions to sunset and sunrise are explored for Where, Who, What, and When. We further compare reactions across different groups, with the aim of quantifying differences in behavior and information spread. Our results suggest that a balanced assessment of landscape preference across different regions and datasets is possible, which strengthens representativity and exploring the How and Why in particular event contexts. The process of analysis is fully documented, allowing transparent replication and adoption to other events or datasets.

Abstract Background Patients with multiple myeloma (MM) were excluded from the original SARS-CoV-2 mRNA vaccine trials, which may influence vaccine hesitancy in this population. We prospectively characterized the safety and immunogenicity of two-dose SARS-CoV-2 mRNA vaccination in 44 patients with MM, who underwent vaccination from 12/17/2020 to 3/18/2021. Results Rates adverse reactions were low and consistent with those documented in vaccine trials. Among those on MM therapy, 93% developed detectable anti-receptor binding domain (RBD) antibodies after dose 2, while 94% of patients not on MM therapy seroconverted. Conclusions Two-dose SARS-CoV-2 mRNA vaccination is mildly reactogenic and leads to high rates of seroconversion in patients with MM. These findings can provide reassurance to MM patients who are hesitant to receive SARS-CoV-2 mRNA vaccines.

IntroductionEvidence of animal personality and behavioral syndromes is widespread across animals, yet the development of these traits remains poorly understood. Previous research has shown that exposure to predators, heterospecifics, and urbanized environments can influence personality and behavioral syndromes. Yet, to date, the influence of early social experiences with conspecifics on the development of adult behavioral traits is far less known. We use swordtail fish (Xiphophorus nigrensis), a species with three genetically-determined male mating strategies (courtship display, coercion, or mixed strategy) to assess how different early-life social experiences shape adult behavioral development.MethodsWe raised female swordtails from birth to adulthood in density-controlled sexual-social treatments that varied in the presence of the type of male mating tactics (coercers only, displayers only, coercers and displayers, and mixed-strategists only). At adulthood, we tested females’ boldness, shyness, aggression, sociality, and activity.ResultsWe found that the number of different mating strategies females were raised with (social complexity) shaped behavioral development more than any individual mating strategy. Females reared in complex environments with two male mating tactics were bolder, less shy, and less aggressive than females reared with a single male mating tactic (either courtship only or coercion only). Complex sexual-social environments produced females with behavioral syndromes (correlations between aggression and activity, shyness and aggression, and social interaction and activity), whereas simple environments did not.DiscussionImportantly, the characteristics of these socially-induced behavioral syndromes differ from those driven by predation, but converge on characteristics emerging from animals found in urban environments. Our findings suggest that complexity of the sexual-social environment shapes the development of personality and behavioral syndromes to facilitate social information gathering. Furthermore, our research highlights the previously overlooked influence of sexual selection as a significant contributing factor to diverse behavioral development.

This study proposes a method that can help in identifying potential locations for improvements of cycling infrastructures. It addresses the need for simple and effective methods to support decision-making in bicycle planning. The city of Paris is used as a case study area because it has made considerable efforts to improve cycling infrastructures and to become more bicycle-friendly in recent years. The method (1) identifies potential locations for improvements of bicycle infrastructures on a street level and (2) on a city level considering accessibility to important destinations. The main data used in this project is street data from OpenStreetMap (OSM) and cycling infrastructure data from the Atelier parisien d’urbanisme (Apur). The proposed method can be applied with commonly available data, has clear outcomes, is reproducible, and can be applied to different case study areas. We produced a map of bicycle suitability across all of Paris, and validated it for the 30 longest segments in the city with lower bike suitability. Our validation showed that combining OSM and Apur data led to a reliable dataset, with which we modelled bikeability using the underlying network overlain on a 250 m resolution grid and destinations representing leisure activities, education, shopping, city functions and public transport. The resulting map identifies regions of the city with poor bikeability, where improvements to cycling infrastructure should be investigated.

Computing trajectory similarity is a fundamental operation in movement analytics, required in search, clustering, and classification of trajectories, for example. Yet the range of different but interrelated trajectory similarity measures can be bewildering for researchers and practitioners alike. This paper describes a systematic comparison and methodical exploration of trajectory similarity measures. Specifically, this paper compares five of the most important and commonly used similarity measures: dynamic time warping (DTW), edit distance (EDR), longest common subsequence (LCSS), discrete Fréchet distance (DFD), and Fréchet distance (FD). The paper begins with a thorough conceptual and theoretical comparison. This comparison highlights the similarities and differences between measures in connection with six different characteristics, including their handling of a relative versus absolute time and space, tolerance to outliers, and computational efficiency. The paper further reports on an empirical evaluation of similarity in trajectories with contrasting properties: data about constrained bus movements in a transportation network, and the unconstrained movements of wading birds in a coastal environment. A set of four experiments: a. creates a measurement baseline by comparing similarity measures to a single trajectory subjected to various transformations; b. explores the behavior of similarity measures on network-constrained bus trajectories, grouped based on spatial and on temporal similarity; c. assesses similarity with respect to known behavioral annotations (flight and foraging of oystercatchers); and d. compares bird and bus activity to examine whether they are distinguishable based solely on their movement patterns. The results show that in all instances both the absolute value and the ordering of similarity may be sensitive to the choice of measure. In general, all measures were more able to distinguish spatial differences in trajectories than temporal differences. The paper concludes with a high-level summary of advice and recommendations for selecting and using trajectory similarity measures in practice, with conclusions spanning our three complementary perspectives: conceptual, theoretical, and empirical.

This article reviews a hermeneutic phenomenological study of five beginning teachers who were introduced to mindfulness during their initial teacher education programme. The participants kept fortnightly journals and engaged in three interviews with the researcher to assess the benefits of using mindfulness during the first year of teaching. The participants in this study discovered through their lived experiences of using mindfulness in their first year of teaching that their personal wellbeing was enhanced, stress was reduced, and they could focus greater attention on their lesson planning and their students. They responded rather than reacted emotionally to student needs. The results of this study suggest that introducing mindfulness in teacher education could enhance the wellbeing of student teachers and beginning teachers and enhance job retention.

Abstract A mouse model of human Familial Adenomatous Polyposis responds favorably to pharmacological inhibition of 5′-methylthioadenosine phosphorylase (MTAP). Methylthio-DADMe-Immucillin-A (MTDIA) is an orally available, transition state analogue inhibitor of MTAP. 5′-Methylthioadenosine (MTA), the substrate for MTAP, is formed in polyamine synthesis and is recycled by MTAP to S-adenosyl-l-methionine (SAM) via salvage pathways. MTDIA treatment causes accumulation of MTA, which inhibits growth of human head and neck (FaDu) and lung (H359, A549) cancers in immunocompromised mouse models. We investigated the efficacy of oral MTDIA as an anti-cancer therapeutic for intestinal adenomas in immunocompetent APCMin/+ mice, a murine model of human Familial Adenomatous Polyposis. Tumors in APCMin/+ mice were decreased in size by MTDIA treatment, resulting in markedly improved anemia and doubling of mouse lifespan. Metabolomic analysis of treated mice showed no changes in polyamine, methionine, SAM or ATP levels when compared with control mice but indicated an increase in MTA, the MTAP substrate. Generation of an MTDIA-resistant cell line in culture showed a four-fold amplification of the methionine adenosyl transferase (MAT2A) locus and expression of this enzyme. MAT2A is downstream of MTAP action and catalyzes synthesis of the SAM necessary for methylation reactions. Immunohistochemical analysis of treated mouse intestinal tissue demonstrated a decrease in symmetric dimethylarginine, a PRMT5-catalyzed modification. The anti-cancer effects of MTDIA indicate that increased cellular MTA inhibits PRMT5-mediated methylations resulting in attenuated tumor growth. Oral dosing of MTDIA as monotherapy has potential for delaying the onset and progression of colorectal cancers in Familial Adenomatous Polyposis (FAP) as well as residual duodenal tumors in FAP patients following colectomy. MTDIA causes a physiologic inactivation of MTAP and may also have efficacy in combination with inhibitors of MAT2A or PRMT5, known synthetic-lethal interactions in MTAP −/− cancer cell lines.

Abstract Background Larvae of the Australian sheep blowfly, Lucilia cuprina, parasitise sheep by feeding on skin excretions, dermal tissue and blood, causing severe damage known as flystrike or myiasis. Recent advances in -omic technologies and bioinformatic data analyses have led to a greater understanding of blowfly biology and should allow the identification of protein families involved in host-parasite interactions and disease. Current literature suggests that proteins of the SCP (Sperm-Coating Protein)/TAPS (Tpx-1/Ag5/PR-1/Sc7) (SCP/TAPS) superfamily play key roles in immune modulation, cross-talk between parasite and host as well as developmental and reproductive processes in parasites. Methods Here, we employed a bioinformatics workflow to curate the SCP/TAPS protein gene family in L. cuprina. Protein sequence, the presence and number of conserved CAP-domains and phylogeny were used to group identified SCP/TAPS proteins; these were compared to those found in Drosophila melanogaster to make functional predictions. In addition, transcription levels of SCP/TAPS protein-encoding genes were explored in different developmental stages. Results A total of 27 genes were identified as belonging to the SCP/TAPS gene family: encoding 26 single-domain proteins each with a single CAP domain and a solitary double-domain protein containing two conserved cysteine-rich secretory protein/antigen 5/pathogenesis related-1 (CAP) domains. Surprisingly, 16 SCP/TAPS predicted proteins formed an extended tandem array spanning a 53 kb region of one genomic region, which was confirmed by MinION long-read sequencing. RNA-seq data indicated that these 16 genes are highly transcribed in all developmental stages (excluding the embryo). Conclusions Future work should assess the potential of selected SCP/TAPS proteins as novel targets for the control of L. cuprina and related parasitic flies of major socioeconomic importance.