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BACKGROUND: The microbiological diagnosis of infectious diarrhoea may take several days using conventional techniques. In order to determine whether flatus can be used to make a rapid diagnosis, the volatile organic compounds associated with diarrhoea were analysed. METHODS: Stool samples were collected from 35 patients with infectious diarrhoea and from six healthy controls. Gaseous compounds were extracted from a headspace using solid phase microextraction and analysed using gas chromatography and mass spectroscopy. RESULTS: Characteristic patterns of volatile gases were found for the main causes of infectious diarrhoea in hospitals. Furan species without indoles indicated Clostridium difficile, ethyl dodecanoate indicated rotavirus, ammonia without ethyl dodecanoate suggested other enteric viruses, and the absence of hydrocarbons and terpenes indicated Campylobacter infection. CONCLUSION: These results could be the basis of rapid near patient diagnosis of infectious diarrhoea. [ABSTRACT FROM AUTHOR]

Surveying seabirds in polar latitudes can be challenging due to sparse human populations, lack of infrastructure and the risk of disturbance to wildlife or damage to habitats. Counting populations using un-crewed aerial vehicles (UAVs) is a promising approach to overcoming these difficulties. However, a careful validation of the approach is needed to ensure comparability with counts collected using conventional methods. Here, we report on surveys of three Antarctic bird species breeding on Signy Island, South Orkney Islands; Chinstrap (Pygoscelis antarctica) and Gentoo (Pygoscelis papua) Penguins, and the South Georgia Shag (Leucocarbo atriceps georgianus). We show that images from low-altitude UAV surveys have sufficient resolution to allow separation of Chinstrap Penguins from contiguously breeding Adélie Penguins (Pygoscelis adéliae), which are very similar in appearance when viewed from overhead. We compare data from ground counts with manual counts of nesting birds on images collected simultaneously by low-altitude aerial photography from multi-rotor UAVs at the same colonies. Results at this long-term monitoring site confirmed a continued population decline for Chinstrap Penguins and increasing Gentoo Penguin population. Although both methods provided breeding pair counts that were generally within ~ 5%, there were significant differences at some locations. We examine these differences in order to highlight potential biases or methodological constraints that should be considered when analysing similar aerial census surveys and comparing them with ground counts. [ABSTRACT FROM AUTHOR]

Remote oceanic islands harbour unique biodiversity, especially of species that rely on the marine trophic resources around their breeding islands. Identifying marine areas used by such species is essential to manage and limit processes that threaten these species. The Tristan da Cunha territory in the South Atlantic Ocean hosts several endemic and globally threatened seabirds, and pinnipeds; how they use the waters surrounding the islands must be considered when planning commercial activities. To inform marine management in the Tristan da Cunha Exclusive Economic Zone (EEZ), we identified statistically significant areas of concentrated activity by collating animal tracking data from nine seabirds and one marine mammal. We first calculated the time that breeding adults of the tracked species spent in 10 × 10 km cells within the EEZ, for each of four seasons to account for temporal variability in space use. By applying a spatial aggregation statistic over these grids for each season, we detected areas that are used more than expected by chance. Most of the activity hotspots were either within 100 km of breeding colonies or were associated with seamounts, being spatially constant across several seasons. Our simple and effective approach highlights important areas for pelagic biodiversity that will benefit conservation planning and marine management strategies. [ABSTRACT FROM AUTHOR]

Background: Despite implementation of enhanced recovery after surgery (ERAS) and laparoscopic techniques, postoperative ileus (POI) remains frequent after colorectal surgery, impacting the patient, their recovery and health‐care resources. Presently there are no tests that reliably predict or enable early POI diagnosis. Volatile organic compounds (VC) are products of human and microbiota cellular metabolism and we hypothesised that a detectable alteration occurs in POI. Method: This was a prospective observational study of patients undergoing laparoscopic colorectal resection within an established ERAS programme. Standardized end‐expiratory breath sampling was performed on the morning of surgery and on the first three postoperative mornings. The concentrations of VCs commonly found in intestinal gas were analysed using selected ion flow tube mass spectrometry and GastroCH4ECK®. Feasibility data, bowel preparation, postoperative oral intake, POI and 30‐day morbidity were recorded. Results: Of the 75 potentially eligible patients, 58 (77%) agreed to participate. Per‐protocol breath sampling was successfully completed in 94%. There were no analytical failures. Baseline and postoperative concentrations of VCs were broadly comparable and were not altered by bowel preparation or postoperative oral intake. POI developed in 14 (29%) patients. Preoperative ammonia concentration was higher in patients who developed POI [830 parts per billion (ppb) vs 510 ppb, P = 0.027]. There was an increase in the concentration of acetic acid detected on day 2 in patients who developed POI (99 ppb vs 171 ppb, P = 0.021). Conclusion: Repeated VC breath sampling and analysis is feasible in the perioperative setting. An elevated ammonia concentration on the morning of surgery may be a potential predictor of POI. [ABSTRACT FROM AUTHOR]

Tracking individual marine predators can provide vital information to aid the identification of important activity (foraging, commuting, rafting, resting, etc.) hotspots and therefore also to delineate priority sites for conservation. However, in certain locations (e.g. Antarctica) many marine mammal or seabird colonies remain untracked due to logistical constraints, and the colonies that are studied may not be the most important in terms of conservation priorities. Using data for one of the most abundant seabirds in the Antarctic as a case study (the Chinstrap Penguin Pygoscelis antarcticus), we tested the use of correlative habitat models (used to predict distribution around untracked colonies) to overcome this limitation, and to enable the identification of important areas at-sea for colonies where tracking data are not available. First, marine Important Bird and Biodiversity Areas (IBA) were identified using a standardised, published approach using empirical data from birds tracked from colonies located in the South Orkney Islands. Subsequently, novel approaches using predicted distributions of Chinstrap Penguins derived from correlative habitat models were applied to identify important marine areas, and the results compared with the IBAs. Data were collected from four colonies over 4 years and during different stages of the breeding season. Results showed a high degree of overlap between the areas identified as important by observed data (IBAs) and by predicted distributions, revealing that habitat preference models can be used to identify marine IBAs for these penguins. We provide a new method for designating a network of marine IBAs for penguins in Antarctic waters, based on outputs from correlative habitat models when tracking data are not available. This can contribute to an evidence-based and precautionary approach to aid the management framework for Antarctic fisheries and for the protection of birds. [ABSTRACT FROM AUTHOR]

Information is needed on how anomalous environmental conditions affect important Antarctic ecological sentinels during the winter. Using a non-invasive method (scats), the diet of non-breeding gentoo penguins Pygoscelis papua at Bird Island, South Georgia, was examined during the winter of 2009 when local environmental conditions were abnormal (e.g. warmer sea surface waters). Scats were collected every 2 weeks from May until October 2009 (N = 168); the diet was dominated by the amphipod Themisto gaudichaudii by frequency of occurrence (77.5% of the samples) and by number (70.5% of the total individuals). By mass, different species of crustaceans (T. gaudichaudii and Antarctic krill Euphausia superba) and fish (Champsocephalus gunnari, Lepidonotothen larseni and Pseudochaenichthys georgianus) were the most important in different periods. Numerically, prey switching occurred at the end of winter, when E. superba became more abundant in the penguins’ diets in late September and early October (austral spring), when sea surface temperatures became colder. T. gaudichaudii is sub-optimal prey for gentoo penguins and its consumption most likely reflects a lack of E. superba in local waters. The consumption of T. gaudichaudii and fish, in place of E. superba, was probably insufficient for the penguins to maintain a body condition suitable for reproduction, contributing to the observed late commencement of breeding (i.e. 2-3 weeks) that year. Our results highlight the sensitivity of gentoo penguin populations to variations in environmental conditions, particularly in terms of how these conditions affect the availability of preferred dietary items and potential follow-on effects in the subsequent breeding season. [ABSTRACT FROM AUTHOR]

Background Inflammatory bowel disease and irritable bowel syndrome may present in a similar manner. Measuring faecal calprotectin concentration is often recommended to rule out inflammatory bowel disease, however, there are no tests to positively diagnose irritable bowel syndrome and invasive tests are still used to rule out other pathologies. Aim To investigate a platform technology for diagnosing inflammatory bowel disease and irritable bowel syndrome based on faecal gas. Methods The platform technology is composed of a gas chromatography column coupled to a metal oxide gas sensor (OdoReader) and a computer algorithm. The OdoReader separates the volatile compounds from faecal gas and the computer algorithm identifies resistance patterns associated with specific medical conditions and builds classification models. This platform was applied to faecal samples from 152 patients: 33 patients with active inflammatory bowel disease; 50 patients with inactive inflammatory bowel disease; 28 patients with irritable bowel syndrome and 41 healthy donors (Control). Results The platform classified samples with accuracies from 75% to 100% using rigorous validation schemes: namely leave-one-out cross-validation, 10-fold cross-validation, double cross-validation and their Monte Carlo variations. The most clinically important findings, after double cross-validation, were the accuracy of active Crohn's disease vs. irritable bowel syndrome (87%; CI 84-89%) and irritable bowel syndrome vs. controls (78%; CI 76-80%). These schemes provide an estimate of out-of-sample predictive accuracy for similar populations. Conclusions This is the first description of an investigation for the positive diagnosis of irritable bowel syndrome, and for diagnosing inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Background The aetiology of inflammatory bowel disease ( IBD) remains poorly understood. Recent evidence suggests an important role of gut microbial dysbiosis in IBD, and this may be associated with changes in faecal volatile organic metabolites ( VOMs). Aim To describe the changes in the faecal VOMs of patients with IBD and establish their diagnostic potential as non-invasive biomarkers. Methods Faecal samples were obtained from 117 people with Crohn's disease ( CD), 100 with ulcerative colitis ( UC), and 109 healthy controls. Faecal VOMs were extracted using solid-phase micro-extraction and analysed by gas chromatography mass spectrometry. Data analysis was carried out using partial least squares-discriminate analysis ( PLS- DA) to determine class membership based on distinct metabolomic profiles. Results The PLS- DA model showed clear separation of active CD from inactive disease and healthy controls ( P < 0.001). Heptanal, 1-octen-3-ol, 2-piperidinone and 6-methyl-2-heptanone were up-regulated in the active CD group [variable important in projection ( VIP) score 2.8, 2.7, 2.6 and 2.4, respectively], while methanethiol, 3-methyl-phenol, short-chain fatty acids and ester derivatives were found to be less abundant ( VIP score of 3.5, 2.6, 1.5 and 1.2, respectively). The PLS- DA model also separated patients with small bowel CD from healthy controls and those with colonic CD from UC ( P < 0.001). In contrast, less distinct separation was observed between active UC, inactive UC and healthy controls. Conclusions Analysis of faecal volatile organic metabolites can provide an understanding of gut metabolomic changes in IBD. It has the potential to provide a non-invasive means of diagnosing IBD, and can differentiate between UC and CD. [ABSTRACT FROM AUTHOR]

The Falkland Islands currently supports one of the largest Southern Rockhopper Penguin ( Eudyptes c. chrysocome) populations. Archipelago-wide censuses conducted in 2000 and 2005 revealed that the number of breeding pairs had declined by 30 % during this period. To establish whether the breeding population continued to decline, an archipelago-wide census was conducted in 2010. We report a conservative estimate of 319,163 ±SD 24,820 pairs breeding at the Falkland Islands in 2010. This represents a 51 % increase when compared with the number counted in 2005. A simple stochastic population model was developed to investigate the extent to which changes in demographic parameters between 2005 and 2010 could account for the increase in breeding pairs. The population model predicted a 38 % increase in the number of breeding pairs over a 5-year period (289,431 ±SD 24,615). The increase in the number of breeding pairs was therefore probably attributed to improved vital rates in the period between the 2005 and 2010 archipelago-wide censuses in combination with other factors such as a reduction in the proportion of adult birds that abstained from breeding. Based on the 2010 Falkland Islands estimate, the global population of the subspecies E. c. chrysocome is now closer to 870,000 breeding pairs of which the Falkland Islands accounts for approximately 36 %, the second largest proportion after Chile. We conclude that despite fluctuations, the number of Southern Rockhopper Penguins breeding at the Falkland Islands has increased over the last 15 years and suggest that the 'Vulnerable' conservation status of the species be re-assessed. [ABSTRACT FROM AUTHOR]

Background Maggot therapy, utilizing the larvae of Lucilia sericata, has been reported to reduce the bacterial load within wounds and also to enhance wound healing. Maggot excretions/secretions (ES) have been shown to have a role in the success of maggot therapy. While the protein content of ES has been investigated, to date little research has focused on the small metabolites present in ES and their potential contribution to the therapy. Study of the molecular composition of the secretions and the potential bioactivities present will allow for a more detailed evaluation of the efficacy of maggot therapy. Objectives We studied the amino acid-like compounds present in ES of L. sericata larvae in order to determine the compounds present and their potential role in the wound healing process. Methods These included thin-layer chromatography/mass spectrometric analysis of ES to identify amino acid-like components, a turbidometric assay to investigate their potential antibacterial activity and cell proliferation studies to investigate their potential mitogenic ability. Results Three prominent compounds were detected and identified as histidine, valinol and 3-guanidinopropionic acid. While these amino acids were not shown to exhibit antibacterial activity, a proliferative effect on the growth of human endothelial cells, but not fibroblasts, was noted. Conclusions The demonstrated proliferative effect, selectively on endothelial cells, suggests that the amino acid-like compounds present in maggot ES may have a role in wound healing, by stimulating angiogenesis. [ABSTRACT FROM AUTHOR]

We report a simple set of chemical reactions based on the reaction of a range of metal salts with potassium ferricyanide loaded gels that spontaneously produce complex and colorful tessellations of the plane. These reactions provide a great resource for scientific demonstrations, whilst also constituting an important class of nonlinear pattern forming reaction. [ABSTRACT FROM AUTHOR]

Volatile organic compounds (VOCs) collected from potato tubers inoculated with Phytophthora infestans (late blight), Fusarium coeruleum (dry rot) or sterilized distilled water (as a control) were analysed using gas chromatography–mass spectrometry (GC–MS) and gas chromatography–flame ionization detection (GC–FID). A total of 52 volatiles were identified by GC–MS in the headspaces above P. infestans- and F. coeruleum-inoculated tubers after incubation for 42 days in the dark at 10°C. Of these VOCs, the six most abundant were common to both pathogens. These were benzothiazole (highest abundance), 2-ethyl-1-hexanol (second highest abundance), and at approximately equal third abundance, hexanal, 2-methylpropanoic acid-2,2-dimethyl-1-(2-hydroxy-1-methylethyl)-propyl ester, 2-methylpropanoic acid-3-hydroxy-2,4,4-trimethyl-pentyl ester and phenol. In addition, styrene also occurred at approximately equal third abundance in the headspace of F. coeruleum-inoculated tubers, but at lower abundance in the headspace of P. infestans-inoculated tubers. Some VOCs were specific to each pathogen. Butanal, 3-methylbutanal, undecane and verbenone were found at low levels only in the headspace of tubers inoculated with P. infestans, while 2-pentylfuran and copaene were found only in the headspace of tubers inoculated with F. coeruleum. Additionally GC–FID analysis identified ethanol and 2-propanol in the liquid exudate from both P. infestans- and F. coeruleum-inoculated tubers after incubation for 35 days, and in the headspace after incubation for 42 days. These data provide key information for developing a sensor-based early warning system for the detection of postharvest diseases in stored potato tubers. [ABSTRACT FROM AUTHOR]

A response from the author of the article "Investigation of faecal volatile organic metabolites as novel diagnostic biomarkers in inflammatory bowel disease" published in the previous issue is presented.

Background: Accurate falls reporting is important in the management of Parkinson's disease. One way in which to improve accuracy is by providing a smartphone app to log fall events. This qualitative study sought to gain insights from healthcare professionals based in the United Kingdom on a novel smartphone application co-developed by people with Parkinson's (PwP) disease for falls reporting. Research Methods: A purposive sample of n=11 healthcare professionals with expertise in Parkinson's were recruited to take part in a focus group to explore their views on the smartphone app. Framework analysis was utilised to interpret the data. Results: Participants discussed the applications role in clinical practice, research, and provided recommendations for future improvements. Within the overarching theme of implementation of iFall in clinical and research practice, three subthemes emerged: (1) applicability to clinical practice, (2) the future of iFall in research and (3) future developments. The application was viewed positively, exhibiting potential to address important contemporary issues within falls reporting and research, whilst being clear, simple and easy to use. Implementation challenges of the application, such as IT integration were highlighted, while enhancements such as voice recognition were suggested. Conclusions: Incorporating suggestions from healthcare professionals and piloting of the application with PwP will increase the likelihood of successful implementation of the iFall app into clinical practice and research., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: RM and JM developed the iFall app.

Background: Fatigue is a prominent symptom in many diseases and is strongly associated with impaired daily function. The measurement of daily function is currently almost always done with questionnaires, which are subjective and imprecise. With the recent advances of digital wearable technologies, novel approaches to evaluate daily function quantitatively and objectively in real-life conditions are increasingly possible. This also creates new possibilities to measure fatigue-related changes of daily function using such technologies., Summary: This review examines which digitally assessable parameters in immune-mediated inflammatory and neurodegenerative diseases may have the greatest potential to reflect fatigue-related changes of daily function., Key Messages: Results of a standardized analysis of the literature reporting about perception-, capacity-, and performance-evaluating assessment tools indicate that changes of the following parameters: physical activity, independence of daily living, social participation, working life, mental status, cognitive and aerobic capacity, and supervised and unsupervised mobility performance have the highest potential to reflect fatigue-related changes of daily function. These parameters thus hold the greatest potential for quantitatively measuring fatigue in representative diseases in real-life conditions, e.g., with digital wearable technologies. Furthermore, to the best of our knowledge, this is a new approach to analysing evidence for the design of performance-based digital assessment protocols in human research, which may stimulate further systematic research in this area., Competing Interests: Meenakshi Chatterjee received stock from employer from Johnson and Johnson and is a full-time employee and shareholder of Johnson and Johnson. Lori Ann Warring is a full-time employee of Johnson and Johnson. Geert van Gassen is a full-time employee of Takeda Belgium. Teemu Ahmaniemi is a full-time employee of VTT Technical Research Centre of Finland Ltd. Michael Chambers received contract funding for all activities related to IDEA-FAST, including contribution to this study/manuscript. Joaquim Ferreira received grants from Angelini, BIAL and AbbVie, and consulting fees or honoraria from Lundbeck, BIAL, Biogen, AbbVie ONO, SK Chemicals, and Zambon. Janneke van der Woude holds grants from AbbVie, Takeda, Pfizer, Galapagos, and Celltrion, and received consulting fees or honoraria from ZonMw, Tramedico, Falk Benelux, and Pfizer. Wan-Fai Ng has provided consultation services for Novartis, GlaxoSmithKline, AbbVie, BMS, Sanofi, MedImmune, argenx, Janssen, Resolve Therapeutics, and UCB., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Objective: The purpose of this study was to coproduce a smart-phone application for digital falls reporting in people with Parkinson disease (PD) and to determine usability using an explanatory mixed-methods approach., Methods: This study was undertaken in 3 phases. Phase 1 was the development phase, in which people with PD were recruited as co-researchers to the project. The researchers, alongside a project advisory group, coproduced the app over 6 months. Phase 2 was the implementation phase, in which 15 people with PD were invited to test the usability of the app. Phase 3 was the evaluation phase, in which usability was assessed using the systems usability scale by 2 focus groups with 10 people with PD from phase 2., Results: A prototype was successfully developed by researchers and the project advisory group. The usability of the app was determined as good (75.8%) by people with PD when rating using the systems usability scale. Two focus groups (n = 5 per group) identified themes of 1) usability, 2) enhancing and understanding management of falls, and 3) recommendations and future developments., Conclusions: A successful prototype of the iFall app was developed and deemed easy to use by people with PD. The iFall app has potential use as a self-management tool for people with PD alongside integration into clinical care and research studies., Impact: This is the first digital outcome tool to offer reporting of falls and near-miss fall events. The app may benefit people with PD by supporting self-management, aiding clinical decisions in practice, and providing an accurate and reliable outcome measure for future research., Lay Summary: A smartphone application designed in collaboration with people who have PD to record their falls was acceptable and easy to use by people with PD., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Physical Therapy Association.)

Aim: This work describes the synthesis and antimicrobial evaluation of 6-aminated 1,4-benzoquinones (6-AQs) against seven resistant pathogens. Materials & methods: The 6-AQs, synthesized via a Michael addition reaction between bromoquinone and p -substituted anilines, were assessed for their antimicrobial activity through both in vitro and in silico analyses. Results: Bromoquinone and 6-AQs with electron-withdrawing groups demonstrated activity against Pseudomonas aeruginosa , with minimum inhibitory concentrations ranging from 16 to 128 μg/ml, comparable to standard antimicrobials. Two derivatives exhibited minimum inhibitory concentrations values against methicillin-resistant Staphylococcus aureus ranging from 64 to 128 μg/ml. These compounds demonstrated both bacteriostatic and bactericidal effects, and antibiofilm features. Conclusion: The 6-AQs 19g and 19f showed a promising antimicrobial profile, indicating their potential as new therapeutic options.

Background: Patient and public involvement and engagement (PPIE) in the design of trials is important, as participant experience critically impacts delivery. The Edmond J Safra Accelerating Clinical Trials in PD (EJS ACT-PD) initiative is a UK consortium designing a platform trial for disease modifying therapies in PD., Objective: The integration of PPIE in all aspects of trial design and its evaluation throughout the project., Methods: PwP and care partners were recruited to a PPIE working group (WG) via UK Parkinson's charities, investigator patient groups and participants of a Delphi study on trial design. They are supported by charity representatives, trial delivery experts, researchers and core project team members. PPIE is fully embedded within the consortium's five other WGs and steering group. The group's terms of reference, processes for effective working and PPIE evaluation were co-developed with PPIE contributors., Results: 11 PwP and 4 care partners have supported the PPIE WG and contributed to the development of processes for effective working. A mixed methods research-in-action study is ongoing to evaluate PPIE within the consortium. This includes the Patient Engagement in Research Scale -a quantitative PPIE quality measure; semi-structured interviews -identifying areas for improvement and overall impressions of involvement; process fidelity- recording adherence; project documentation review - identifying impact of PPIE on project outputs., Conclusions: We provide a practical example of PPIE in complex projects. Evaluating feasibility, experiences and impact of PPIE involvement in EJS ACT-PD will inform similar programs on effective strategies. This will help enable future patient-centered research.

Background: In support of UCB pharmaceutical research programs, the aim of this research was to implement a novel process for patient involvement in a multidisciplinary research group to co-create a clinical outcome assessment strategy to accurately reflect the experience of people living with early-stage Parkinson's. Patient experts were an integral part of the decision-making process for patient-reported outcome (PRO) research and instrument development., Methods: In partnership with two patient organizations (Parkinson's UK and the Parkinson's Foundation), 6 patient experts were recruited into a multidisciplinary research group alongside clinical, patient engagement and involvement, regulatory science, and outcome measurement experts. The group was involved across two phases of research; the first phase identified what symptoms are cardinal to the experience of living with early-stage Parkinson's and the second phase involved the development of PRO instruments to better assess the symptoms that are important to people living with early-stage Parkinson's. Patient experts were important in performing a variety of roles, in particular, qualitative study protocol design, conceptual model development, and subsequent co-creation of two PRO instruments., Results: Involving people with Parkinson's in PRO research ensured that the expertise of these representatives from the Parkinson's community shaped and drove the research; as such, PRO instruments were being developed with the patient at the forefront. Working with patient experts required considerable resource and time allocation for planning, communication, document development, and organizing meetings; however, their input enriched the development of PRO instruments and was vital in developing PRO instruments that are more meaningful for people with Parkinson's and clinicians., Conclusions: Conducting PRO research, in the context of clinical development involving pharmaceutical companies, requires balancing regulatory and scientific rigor with tight time constraints. Incorporating a multi-stakeholder perspective, which included patient experts as joint investigators, had a strong positive impact on our research, despite the logistical complexities of their involvement. Due to the input of patient experts, the innovative clinical outcome assessment strategy and the co-created novel PRO instruments were more relevant and holistic to the patient experience of early-stage Parkinson's., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Previous research on concepts that are important to people living with early-stage Parkinson's indicated that 'functional' slowness, fine motor skills, and subtle gait abnormalities are cardinal concepts that are not comprehensively captured by existing patient-reported outcome (PRO) instruments that are used in clinical practice and research to assess symptoms and daily functioning within this patient population. We sought to develop novel PRO instruments to address this unmet need., Methods: PRO instrument development was led by a multidisciplinary research group, including people living with Parkinson's (termed 'patient experts'), as well as patient engagement and involvement, regulatory science, clinical, and outcome measurement experts. A first set of PRO instruments, termed Early Parkinson's Function Slowness (42 items) and Early Parkinson's Mobility (26 items), were drafted to capture 'functional' slowness, fine motor skills, and subtle gait abnormalities. These PRO instruments were used in cognitive debriefing interviews with people living with early-stage Parkinson's (who were not involved with the multidisciplinary research group) to identify issues with relevance, clarity, ease of completion, conceptual overlap, or missing concepts., Results: Sixty people living with early-stage Parkinson's were interviewed, which led to refining the items to 45 for the Early Parkinson's Functional Slowness and 23 for the Early Parkinson's Mobility PRO instruments. Refinement included rewording items to address clarity issues, merging or splitting items to address overlap issues, and adding new items to address missing concepts. The Early Parkinson's Function Slowness PRO instrument resulted in a multidimensional instrument covering upper limb, complex/whole body, general activity, and cognitive functional slowness. The Early Parkinson's Mobility PRO instrument resulted in comprehensive coverage of everyday mobility tasks, with a focus on gait concepts, plus complex/whole body, balance, and lower limb mobility., Conclusions: The Early Parkinson's Function Slowness and Early Parkinson's Mobility PRO instruments aim to address gaps in existing PRO instruments to measure meaningful symptoms and daily functioning in people living with early-stage Parkinson's. Utilizing a meticulous study design led by a multidisciplinary research group that included patient experts helped to ensure that the PRO instruments were patient-centric, content valid, and meaningful from a clinical and measurement perspective., (© 2023. The Author(s).)

Anthropogenic climate change is resulting in spatial redistributions of many species. We assessed the potential effects of climate change on an abundant and widely distributed group of diving birds, Eudyptes penguins, which are the main avian consumers in the Southern Ocean in terms of biomass consumption. Despite their abundance, several of these species have undergone population declines over the past century, potentially due to changing oceanography and prey availability over the important winter months. We used light-based geolocation tracking data for 485 individuals deployed between 2006 and 2020 across 10 of the major breeding locations for five taxa of Eudyptes penguins. We used boosted regression tree modelling to quantify post-moult habitat preference for southern rockhopper (E. chrysocome), eastern rockhopper (E. filholi), northern rockhopper (E. moseleyi) and macaroni/royal (E. chrysolophus and E. schlegeli) penguins. We then modelled their redistribution under two climate change scenarios, representative concentration pathways RCP4.5 and RCP8.5 (for the end of the century, 2071-2100). As climate forcings differ regionally, we quantified redistribution in the Atlantic, Central Indian, East Indian, West Pacific and East Pacific regions. We found sea surface temperature and sea surface height to be the most important predictors of current habitat for these penguins; physical features that are changing rapidly in the Southern Ocean. Our results indicated that the less severe RCP4.5 would lead to less habitat loss than the more severe RCP8.5. The five taxa of penguin may experience a general poleward redistribution of their preferred habitat, but with contrasting effects in the (i) change in total area of preferred habitat under climate change (ii) according to geographic region and (iii) the species (macaroni/royal vs. rockhopper populations). Our results provide further understanding on the regional impacts and vulnerability of species to climate change., (© 2022 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

Density-dependent prey depletion around breeding colonies has long been considered an important factor controlling the population dynamics of colonial animals. 1-4 Ashmole proposed that as seabird colony size increases, intraspecific competition leads to declines in reproductive success, as breeding adults must spend more time and energy to find prey farther from the colony. 1 Seabird colony size often varies over several orders of magnitude within the same species and can include millions of individuals per colony. 5 , 6 As such, colony size likely plays an important role in determining the individual behavior of its members and how the colony interacts with the surrounding environment. 6 Using tracking data from murres (Uria spp.), the world's most densely breeding seabirds, we show that the distribution of foraging-trip distances scales to colony size 0 .33 during the chick-rearing stage, consistent with Ashmole's halo theory. 1 , 2 This pattern occurred across colonies varying in size over three orders of magnitude and distributed throughout the North Atlantic region. The strong relationship between colony size and foraging range means that the foraging areas of some colonial species can be estimated from colony sizes, which is more practical to measure over a large geographic scale. Two-thirds of the North Atlantic murre population breed at the 16 largest colonies; by extrapolating the predicted foraging ranges to sites without tracking data, we show that only two of these large colonies have significant coverage as marine protected areas. Our results are an important example of how theoretical models, in this case, Ashmole's version of central-place-foraging theory, can be applied to inform conservation and management in colonial breeding species., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Body re-sizing illusions can profoundly alter perception of our own body. We investigated whether creating the illusion of a muscled and fit-looking back (Strong) influenced perceived back size, body ownership, and attitudes towards self-capacity during a lifting task. Twenty-four healthy male volunteers performed a standardised lifting task while viewing real-time (delay < 20 ms) video of their own back through a head-mounted display under four different conditions (Normal size, Strong, Reshaped, Large; order randomised). The MIRAGE-mediated reality system was used to modify the shape, size, and morphology of the back. Participants were poor at recognizing the correct appearance of their back, for both implicit (perceived width of shoulders and hips) and explicit (questionnaire) measures of back size. Visual distortions of body shape (Reshaped condition) altered implicit back size measures. However, viewing a muscled back (Strong condition) did not result in a sense of agency or ownership and did not update implicit perception of the back. No conditions improved perceptions/attitudes of self-capacity (perceived back strength, perceived lifting confidence, and perceived back fitness). The results lend support for the importance of the embodiment of bodily changes to induce changes in perception. Further work is warranted to determine whether increased exposure to illusory changes would alter perceptions and attitudes towards self-capacity or whether different mechanisms are involved., (© 2021. The Author(s).)

Introduction: Qualitative research on patient experiences in early-stage Parkinson's disease (PD) is limited. It is increasingly acknowledged that clinical outcome assessments used in trials do not fully capture the range of symptoms/impacts that are meaningful to people with early-stage PD. We aimed to conceptualize the patient experience in early-stage PD and identify, from the patient perspective, those cardinal symptoms/impacts which might be more useful to measure in clinical trials., Methods: In a mixed-methods analysis, 50 people with early-stage PD and nine relatives were interviewed. Study design and results interpretation were led by a multidisciplinary group of patient, clinical, regulatory, and outcome measurements experts, and patient organization representatives. Identification of the cardinal concepts was informed by the relative frequency of reported concepts combined with insights from patient experts and movement disorder specialists., Results: A conceptual model of the patient experience of early-stage PD was developed. Concept elicitation generated 145 unique concepts mapped across motor and non-motor symptoms, function, and impacts. Bradykinesia/slowness (notably in the form of "functional slowness"), tremor, rigidity/stiffness, mobility (particularly fine motor dexterity and subtle gait abnormalities), fatigue, depression, sleep/dreams, and pain were identified as cardinal in early-stage PD. "Functional slowness" (related to discrete tasks involving the upper limbs, complex mobility tasks, and general activities) was deemed to be more relevant than "difficulty" to patients with early-stage PD, who report being slower at completing tasks rather than encountering significant impairment with task completion., Conclusion: Patient experiences in early-stage PD are complex and wide-ranging, and the currently available patient-reported outcome (PRO) instruments do not evaluate many early-stage PD concepts such as functional slowness, fine motor skills, and subtle gait abnormalities. The development of a new PRO instrument, created in conjunction with people with PD, that fully assesses symptoms and the experience of living with early-stage PD, is required., (© 2022. The Author(s).)

Background: The diagnosis and surveillance of urothelial bladder cancer (UBC) require cystoscopy. There is a need for biomarkers to reduce the frequency of cystoscopy in surveillance; urinary volatile organic compound (VOC) analysis could fulfil this role. This cross-sectional study compared the VOC profiles of patients with and without UBC, to investigate metabolomic signatures as biomarkers., Methods: Urine samples were collected from haematuria clinic patients undergoing diagnostic cystoscopy and UBC patients undergoing surveillance. Urinary headspace sampling utilised solid-phase microextraction and VOC analysis applied gas chromatography-mass spectrometry; the output underwent metabolomic analysis., Results: The median participant age was 70 years, 66.2% were male. Of the haematuria patients, 21 had a new UBC diagnosis, 125 had no cancer. In the surveillance group, 75 had recurrent UBC, 84 were recurrence-free. A distinctive VOC profile was observed in UBC patients compared with controls. Ten VOCs had statistically significant abundances useful to classify patients (false discovery rate range 1.9 × 10 -7 -2.8 × 10 -2 ). Two prediction models were evaluated using internal validation. An eight-VOC diagnostic biomarker panel achieved AUROC 0.77 (sensitivity 0.71, specificity 0.72). A six-VOC surveillance biomarker panel obtained AUROC 0.80 (sensitivity 0.71 and specificity 0.80)., Conclusions: Urinary VOC analysis could aid the diagnosis and surveillance of UBC., (© 2022. The Author(s).)

Background: Pain in Parkinson's is problematic but under treated in clinical practice. Healthcare professionals must understand the impact of pain in Parkinson's and patient preferences for management., Objective: To understand the impact of pain in Parkinson's and to understand current management and preferences for pain management., Methods: We conducted a national survey with 115 people with Parkinson's (PwP) and 10 carers. Both closed and open questions were used. The questions focused on how pain affected the individual, healthcare professional involvement in supporting pain management, current pain management strategies and views on future pain management interventions. We used descriptive statistics to summarize closed responses and thematic analysis to summarize open question responses., Results: 70% of participants reported pain impacted their daily life. Pain had a multifactorial impact on participants, affecting movement, mood and quality of life. Improved pain management was viewed to have the potential to address each of these challenges. Pain affected a number of different sites, with low back pain and multiple sites being most frequently reported. Exercise was the most frequently noted strategy (38%) recommended by healthcare professionals for pain management. PwP would value involvement from healthcare professionals for future pain management, but also would like to self-manage the condition. Medication was not suggested as a first line strategy., Conclusions: Despite reporting engagement in some strategies to manage pain, pain still has a wide-ranging impact on the daily life of PwP. Results from this survey highlight the need to better support PwP to manage the impact of pain.

Changes in phenology and distribution are being widely reported for many migratory species in response to shifting environmental conditions. Understanding these changes and the situations in which they occur can be aided by understanding consistent individual differences in phenology and distribution and the situations in which consistency varies in strength or detectability. Studies tracking the same individuals over consecutive years are increasingly reporting migratory timings to be a repeatable trait, suggesting that flexible individual responses to environmental conditions may contribute little to population-level changes in phenology and distribution. However, how this varies across species and sexes, across the annual cycle and in relation to study (tracking method, study design) and/or ecosystem characteristics is not yet clear. Here, we take advantage of the growing number of publications in movement ecology to perform a phylogenetic multilevel meta-analysis of repeatability estimates for avian migratory timings to investigate these questions. Of 2,433 reviewed studies, 54 contained suitable information for meta-analysis, resulting in 177 effect sizes from 47 species. Individual repeatability of avian migratory timings averaged 0.414 (95% confidence interval: 0.3-0.5) across landbirds, waterbirds and seabirds, suggesting consistent individual differences in migratory timings is a common feature of migratory systems. Timing of departure from the non-breeding grounds was more repeatable than timings of arrival at or departure from breeding grounds, suggesting that conditions encountered on migratory journeys and outcome of breeding attempts can influence individual variation. Population-level shifts in phenology could arise through individual timings changing with environmental conditions and/or through shifts in the numbers of individuals with different timings. Our findings suggest that, in addition to identifying the conditions associated with individual variation in phenology, exploring the causes of between-individual variation will be key in predicting future rates and directions of changes in migratory timings. We therefore encourage researchers to report the within- and between- individual variance components underpinning the reported repeatability estimates to aid interpretation of migration behaviour. In addition, the lack of studies in the tropics means that levels of repeatability in less strongly seasonal environments are not yet clear., (© 2022 The Authors. Journal of Animal Ecology published by John Wiley & Sons Ltd on behalf of British Ecological Society.)

Colorectal symptoms are common but only infrequently represent serious pathology, including colorectal cancer (CRC). A large number of invasive tests are presently performed for reassurance. We investigated the feasibility of urinary volatile organic compound (VOC) testing as a potential triage tool in patients fast-tracked for assessment for possible CRC. A prospective, multi-center, observational feasibility study was performed across three sites. Patients referred to NHS fast-track pathways for potential CRC provided a urine sample that underwent Gas Chromatography-Mass Spectrometry (GC-MS), Field Asymmetric Ion Mobility Spectrometry (FAIMS), and Selected Ion Flow Tube Mass Spectrometry (SIFT-MS) analysis. Patients underwent colonoscopy and/or CT colonography and were grouped as either CRC, adenomatous polyp(s), or controls to explore the diagnostic accuracy of VOC output data supported by an artificial neural network (ANN) model. 558 patients participated with 23 (4%) CRC diagnosed. 59% of colonoscopies and 86% of CT colonographies showed no abnormalities. Urinary VOC testing was feasible, acceptable to patients, and applicable within the clinical fast track pathway. GC-MS showed the highest clinical utility for CRC and polyp detection vs. controls (sensitivity = 0.878, specificity = 0.882, AUROC = 0.896) but it is labour intensive. Urinary VOC testing and analysis are feasible within NHS fast-track CRC pathways. Clinically meaningful differences between patients with cancer, polyps, or no pathology were identified suggesting VOC analysis may have future utility as a triage tool.

Background: In migratory species, the extent of within- and between-individual variation in migratory strategies can influence potential rates and directions of responses to environmental changes. Quantifying this variation requires tracking of many individuals on repeated migratory journeys. At temperate and higher latitudes, low levels of within-individual variation in migratory behaviours are common and may reflect repeated use of predictable resources in these seasonally-structured environments. However, variation in migratory behaviours in the tropics, where seasonal predictability of food resources can be weaker, remains largely unknown., Methods: Round Island petrels (Pterodroma sp.) are tropical, pelagic seabirds that breed all year round and perform long-distance migrations. Using multi-year geolocator tracking data from 62 individuals between 2009 and 2018, we quantify levels of within- and between-individual variation in non-breeding distributions and timings., Results: We found striking levels of between-individual variation in at-sea movements and timings, with non-breeding migrations to different areas occurring across much of the Indian Ocean and throughout the whole year. Despite this, repeat-tracking of individual petrels revealed remarkably high levels of spatial and temporal consistency in within-individual migratory behaviour, particularly for petrels that departed at similar times in different years and for those departing in the austral summer. However, while the same areas were used by individuals in different years, they were not necessarily used at the same times during the non-breeding period., Conclusions: Even in tropical systems with huge ranges of migratory routes and timings, our results suggest benefits of consistency in individual migratory behaviours. Identifying the factors that drive and maintain between-individual variation in migratory behaviour, and the consequences for breeding success and survival, will be key to understanding the consequences of environmental change across migratory ranges., (© 2022. The Author(s).)

Background: COVID-19 has placed unprecedented demands on hospitals. A clinical service, COVID-19 Oximetry @home (CO@h) was launched in November 2020 to support remote monitoring of COVID-19 patients in the community. Remote monitoring through CO@h aims to identify early patient deterioration and provide timely escalation for cases of silent hypoxia, while reducing the burden on secondary care., Methods: We conducted a retrospective service evaluation of COVID-19 patients onboarded to CO@h from November 2020 to March 2021 in the North Hampshire (UK) community led service (a collaboration of 15 General Practitioner (GP) practices covering 230 000 people). We have compared outcomes for patients admitted to Basingstoke and North Hampshire Hospital who were CO@h patients (COVID-19 patients with home monitoring of oxygen saturation (SpO 2 ; n=115), with non-CO@h patients (those directly admitted without being monitored by CO@h (n=633)). Crude and adjusted OR analysis was performed to evaluate the effects of CO@h on patient outcomes of 30-day mortality, Intensive care unit (ICU) admission and hospital length of stay greater than 3, 7, 14 and 28 days., Results: Adjusted ORs for CO@h show an association with a reduction for several adverse patient outcome: 30-day hospital mortality (p<0.001, OR 0.21, 95% CI 0.08 to 0.47), hospital length of stay larger than 3 days (p<0.05, OR 0.62, 95% CI 0.39 to 1.00), 7 days (p<0.001, OR 0.35, 95% CI 0.22 to 0.54), 14 days (p<0.001, OR 0.22 95% CI, 0.11 to 0.41), and 28 days (p<0.05, OR 0.21, 95% CI 0.05 to 0.59). No significant reduction ICU admission was observed (p>0.05, OR 0.43, 95% CI 0.15 to 1.04). Within 30 days of hospital admission, there were no hospital readmissions for those on the CO@h service as opposed to 8.7% readmissions for those not on the service., Conclusions: We have demonstrated a significant association between CO@h and better patient outcomes; most notably a reduction in the odds of hospital lengths of stays longer than 7, 14 and 28 days and 30-day hospital mortality., Competing Interests: Competing interests: MI-K is National Clinical Lead Deterioration & National Specialist Advisor Sepsis, NHS England and NHS Improvement., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Mechanisms promoting coexistence between closely related species are fundamental for maintaining species diversity. Mechanisms of niche differentiation include allochrony which offsets the peak timing of resource utilisation between species. Many studies focus on spatial and temporal niche partitioning during the breeding season, few have investigated the role allochrony plays in influencing interspecific segregation of foraging distribution and ecology between congeneric species during the non-breeding season. We investigated the non-breeding migrations of Snares (Eudyptes robustus) and Fiordland penguins (Eudyptes pachyrhynchus), closely related species breeding between 100-350 km apart whose migration phenology differs by two months. Using light geolocation tracking, we examined the degree of overlap given the observed allochrony and a hypothetical scenario where the species commence migration simultaneously. We found that Fiordland penguins migrated to the Sub-Antarctic Frontal Zone and Polar Frontal Zone in the austral autumn whereas Snares penguins disperse westwards staying north of the Sub-Tropical Front in the austral winter. Our results suggest that allochrony is likely to be at the root of segregation because the relative profitability of the different water masses that the penguins forage in changes seasonally which results in the two species utilising different areas over their core non-breeding periods. Furthermore, allochrony reduces relatively higher levels of spatiotemporal overlap during the departure and arrival periods, when the close proximity of the two species' colonies would cause the birds to congregate in similar areas, resulting in high interspecific competition just before the breeding season. Available evidence from other studies suggests that the shift in phenology between these species has arisen from adaptive radiation and phenological matching to the seasonality of local resource availability during the breeding season and reduced competitive overlap over the non-breeding season is likely to be an incidental outcome., Competing Interests: The authors have declared that no competing interests exist. The commercial affiliations of authors KP, PGB and KWM does not alter our adherence to PLOS ONE policies on sharing data and materials.

Climate change alters species distributions by shifting their fundamental niche in space through time. Such effects may be exacerbated by increased inter-specific competition if climate alters species dominance where competitor ranges overlap. This study used census data, telemetry and stable isotopes to examine the population and foraging ecology of a pair of Arctic and temperate congeners across an extensive zone of sympatry in Iceland, where sea temperatures varied substantially. The abundance of Arctic Brünnich's guillemot Uria lomvia declined with sea temperature. Accessibility of refugia in cold water currents or fjords helped support higher numbers and reduce rates of population decline. Competition with temperate Common guillemots Uria aalge did not affect abundance, but similarities in foraging ecology were sufficient to cause competition when resources are limiting. Continued warming is likely to lead to further declines of Brünnich's guillemot, with implications for conservation status and ecosystem services., (© 2021. The Author(s).)

Background: Microbial resistance has become a worldwide public health problem and may lead to morbidity and mortality in affected patients., Objectives: Therefore, this work aimed to evaluate the antibacterial activity of quinone-4- oxoquinoline derivatives., Methods: These derivatives were evaluated against Gram-positive and Gram-negative bacteria by their antibacterial activity, anti-biofilm, and hemolytic activities and in silico assays., Results: The quinone-4-oxoquinoline derivatives presented broad-spectrum antibacterial activities and, in some cases, were more active than commercially available reference drugs. These compounds also inhibited bacterial adhesion, and the assays revealed seven non-hemolytic derivatives. The derivatives seem to cause damage to the bacterial cell membrane, and those containing the carboxyl group at the C-3 position of the 4-quinolonic nucleus were more active than those containing a carboxyethyl group., Conclusion: The isoquinoline-5,8-dione nucleus also favored antimicrobial activity. The study showed that the target of the derivatives must be a non-conventional hydrophobic allosteric binding pocket on the DNA gyrase enzyme., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Static (fixed-boundary) protected areas are key ocean conservation strategies, and marine higher predator distribution data can play a leading role toward identifying areas for conservation action. The Falkland Islands are a globally significant site for colonial breeding marine higher predators (i.e., seabirds and pinnipeds). However, overlap between marine predators and Falkland Islands proposed Marine Managed Areas (MMAs) has not been quantified. Hence, to provide information required to make informed decisions regarding the implementation of proposed MMAs, our aims were to objectively assess how the proposed MMA network overlaps with contemporary estimates of marine predator distribution. We collated tracking data (1999-2019) and used a combination of kernel density estimation and model-based predictions of spatial usage to quantify overlap between colonial breeding marine predators and proposed Falkland Islands MMAs. We also identified potential IUCN Key Biodiversity Areas (pKBAs) using (1) kernel density based methods originally designed to identify Important Bird and Biodiversity Areas (IBAs) and (2) habitat preference models. The proposed inshore MMA, which extends three nautical miles from the Falkland Islands, overlapped extensively with areas used by colonial breeding marine predators. This reflects breeding colonies being distributed throughout the Falklands archipelago, and use being high adjacent to colonies due to central-place foraging constraints. Up to 45% of pKBAs identified via kernel density estimation were located within the proposed MMAs. In particular, the proposed Jason Islands Group MMA overlapped with pKBAs for three marine predator species, suggesting it is a KBA hot spot. However, tracking data coverage was incomplete, which biased pKBAs identified using kernel density methods, to colonies tracked. Moreover, delineation of pKBA boundaries were sensitive to the choice of smoothing parameter used in kernel density estimation. Delineation based on habitat model predictions for both sampled and unsampled colonies provided less biased estimates, and revealed 72% of the Falkland Islands Conservation Zone was likely a KBA. However, it may not be practical to consider such a large area for fixed-boundary management. In the context of wide-ranging marine predators, emerging approaches such as dynamic ocean management could complement static management frameworks such as MMAs, and provide protection at relevant spatiotemporal scales., (© 2021 by the Ecological Society of America.)

Mass spectrometry (MS) is an analytical technique that can be used for various applications in a number of scientific areas including environmental, security, forensic science, space exploration, agri-food, and numerous others. MS is also continuing to offer new insights into the proteomic and metabolomic fields. MS techniques are frequently used for the analysis of volatile compounds (VCs). The detection of VCs from human samples has the potential to aid in the diagnosis of diseases, in monitoring drug metabolites, and in providing insight into metabolic processes. The broad usage of MS has resulted in numerous variations of the technique being developed over the years, which can be divided into hyphenated and real-time MS techniques. Hyphenated chromatographic techniques coupled with MS offer unparalleled qualitative analysis and high accuracy and sensitivity, even when analysing complex matrices (breath, urine, stool, etc.). However, these benefits are traded for a significantly longer analysis time and a greater need for sample preparation and method development. On the other hand, real-time MS techniques offer highly sensitive quantitative data. Additionally, real-time techniques can provide results in a matter of minutes or even seconds, without altering the sample in any way. However, real-time MS can only offer tentative qualitative data and suffers from molecular weight overlap in complex matrices. This review compares hyphenated and real-time MS methods and provides examples of applications for each technique for the detection of VCs from humans.