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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.

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.

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.

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 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.

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 .