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Preclinical Evaluation of the Neutralising Efficacy of Three Monospecific Antivenoms Against the Venoms of Five African Echis Species, Including the Recently Partitioned E. ocellatus and E. romani
Get PDFBackground: The genus Echis is of high medical importance across Africa. Recently the taxonomy of its most medically important species, Echis ocellatus, underwent a revision, resulting in a splitting of the species into E. romani and E. ocellatus, and leading to uncertainty of the efficacy of antivenoms indicated for treatment of ‘E. ocellatus’ envenomings against the two redefined species.Methods: We compared the in vitro and murine preclinical venom-neutralising efficacy of three antivenoms (EchiTAbG, SAIMR Echis and Echiven) raised against E. ocellatus sensu lato against the venoms of E. romani and E. ocellatus, and investigated cross-reactivity to E. coloratus, E. leucogaster, and E. pyramidum leakeyi.Findings: In preclinical assays of envenoming, all three antivenoms neutralised Nigerian E. romani venom, though all three were less protective against Cameroonian E. romani. SAIMR Echis and Echiven neutralised E. ocellatus venom whereas EchiTAbG was less protective. SAIMR Echis and Echiven showed strong cross-reactivity to E. p. leakeyi and E. leucogaster, whilst EchiTAbG showed weaker cross-reactivity. All three antivenoms exhibited poor neutralisation of E. coloratus venom.Interpretation: This represents the first detailed analysis of differences between E. ocellatus and E. romani venom bioactivities and the impact of antivenom on these two species. Our findings demonstrate that SAIMR Echis and Echiven antivenoms are preclinically efficacious against the lethal effects of several species of Echis. These products, in addition to EchiTAbG, seem likely to meet the WHO recommendation of three antivenoms required for treatment of Echis envenomings across sub-Saharan Africa, though clinical evidence is required to confirm these findings
Evaluating the effect of a digital health intervention to enhance physical activity in people with chronic kidney disease (Kidney BEAM): a multicentre, randomised controlled trial in the UK
Get PDFBackgroundRemote digital health interventions to enhance physical activity provide a potential solution to improve the sedentary behaviour, physical inactivity, and poor health-related quality of life that are typical of chronic conditions, particularly for people with chronic kidney disease. However, there is a need for high-quality evidence to support implementation in clinical practice. The Kidney BEAM trial evaluated the clinical effect of a 12-week physical activity digital health intervention on health-related quality of life.MethodsIn a single-blind, randomised controlled trial conducted at 11 centres in the UK, adult participants (aged ≥18 years) with chronic kidney disease were recruited and randomly assigned (1:1) to the Kidney BEAM physical activity digital health intervention or a waiting list control group. Randomisation was performed with a web-based system, in randomly permuted blocks of six. Outcome assessors were masked to treatment allocation. The primary outcome was the difference in the Kidney Disease Quality of Life Short Form version 1.3 Mental Component Summary (KDQoL-SF1.3 MCS) between baseline and 12 weeks. The trial was powered to detect a clinically meaningful difference of 3 arbitrary units (AU) in KDQoL-SF1.3 MCS. Outcomes were analysed by an intention-to-treat approach using an analysis of covariance model, with baseline measures and age as covariates. The trial was registered with ClinicalTrials.gov, NCT04872933.FindingsBetween May 6, 2021, and Oct 30, 2022, 1102 individuals were assessed for eligibility, of whom 340 participants were enrolled and randomly assigned to the Kidney BEAM intervention group (n=173) or the waiting list control group (n=167). 268 participants completed the trial (112 in the Kidney BEAM group and 156 in the waiting list control group). All 340 randomly assigned participants were included in the intention-to treat population. At 12 weeks, there was a significant improvement in KDQoL-SF.13 MCS score in the Kidney BEAM group (from mean 44·6 AU [SD 10·8] at baseline to 47·0 AU [10·6] at 12 weeks) compared with the waiting list control group (from 46·1 AU [10·5] to 45·0 AU [10·1]; between-group difference of 3·1 AU [95% CI 1·8–4·4]; p<0·0001).InterpretationThe Kidney BEAM physical activity platform is an efficacious digital health intervention to improve mental health-related quality of life in patients with chronic kidney disease. These findings could facilitate the incorporation of remote digital health interventions into clinical practice and offer a potential intervention worthy of investigation in other chronic conditions.FundingKidney Research UK.<br/
Physics-Based Modeling for Hybrid Data-Driven Models to Estimate SNR in WDM Systems
Get PDFRecently several machine learning methods have been proposed to estimate the SNR, based on launch data and other system factors. These data-driven methods typically require a large number of datasets for training and generally are not interpretable. In this paper, we propose an alternative approach that requires less data and is interpretable, specifically a hybrid algorithm combining a physical model with Gaussian process regression. We develop a measurement-informed physical model, systematically reducing the number of independent parameters based on the underpinning physics and improve the overall performance of the physical model marginally. The model is validated using measurements performed on a 15-channel wavelength-division multiplexed system propagating over 1,000 km of standard single-mode fiber. The proposed hybrid model is not only interpretable but also obtains better agreement with measurements than a Gaussian process regression model and a simple neural network model for a given number of training datapoints
Variation in farming damselfish behaviour creates a competitive landscape of risk on coral reefs
Get PDFInterspecific interactions are fundamental drivers of animal space use. Yet while non-consumptive effects of predation risk on prey space use are well-known, the risk of aggressive interactions on space use of competitors is largely unknown. We apply the landscape of risk framework to competition-driven space use for the first time, with the hypothesis that less aggressive competitors may alter their behaviour to avoid areas of high competitor density. Specifically, we test how aggressive risk from territorial algal-farming damselfishes can shape the spatial distribution of herbivore fish competitors. We found that only the most aggressive damselfish had fewer competitors in their surrounding area, demonstrating that individual-level behavioural variation can shape spatial distributions. In contradiction to the landscape of risk framework, abundances of farming damselfish and other fishes were positively associated. Our results suggest that reef fishes do not simply avoid areas of high damselfish abundance, but that spatial variation in aggressive behaviour, rather than of individuals, created a competitive landscape of risk. We emphasize the importance of individual-level behaviour in identifying patterns of space use and propose expanding the landscape of risk framework to non-predatory interactions to explore cascading behavioural responses to aggressive risk
The New Feminist Series: Cha(lle)nging the Representation of the Postfeminist Woman in Spanish Television (2015–2022)
Get PDFUnravelling the complexities of biotic homogenization and heterogenization in the British avifauna
Get PDFAbstract Biotic homogenization is a process whereby species assemblages become more similar through time. The standard way of identifying the process of biotic homogenization is to look for decreases in spatial beta?diversity. However, using a single assemblage-level metric to assess homogenization can mask important changes in the occupancy patterns of individual species. Here, we analysed changes in the spatial beta?diversity patterns (i.e. biotic heterogenization or homogenization) of British bird assemblages within 30?km???30?km regions between two periods (1988?1991 and 2008?2011). We partitioned the change in spatial beta?diversity into extirpation and colonization-resultant change (i.e. change in spatial beta?diversity within each region resulting from both extirpation and colonization). We used measures of abiotic change in combination with Bayesian modelling to disentangle the drivers of biotic heterogenization and homogenization. We detected both heterogenization and homogenization across the two time periods and three measures of diversity (taxonomic, phylogenetic, and functional). In addition, both extirpation and colonization contributed to the observed changes, with heterogenization mainly driven by extirpation and homogenization by colonization. These assemblage-level changes were primarily due to shifting occupancy patterns of generalist species. Compared to habitat generalists, habitat specialists had significantly (i) higher average contributions to colonization-resultant change (indicating heterogenization within a region due to colonization) and (ii) lower average contributions to extirpation-resultant change (indicating homogenization from extirpation). Generalists showed the opposite pattern. Increased extirpation-resultant homogenization within regions was associated with increased urban land cover and decreased habitat diversity, precipitation, and temperature. Changes in extirpation-resultant heterogenization and colonization-resultant heterogenization were associated with differences in elevation between regions and changes in temperature and land cover. Many of the ?winners? (i.e. species that increased in occupancy) were species that had benefitted from conservation action (e.g. buzzard (Buteo buteo)). The ?losers? (i.e. those that decreased in occupancy) consisted primarily of previously common species, such as cuckoo (Cuculus canorus). Our results show that focusing purely on changes in spatial beta?diversity over time may obscure important information about how changes in the occupancy patterns of individual species contribute to homogenization and heterogenization
Climatic zone effects of non-native plant invasion on CH4 and N2O emissions from natural wetland ecosystems
Get PDFPlant invasion can significantly alter the carbon and nitrogen cycles of wetlands, which potentially affects the emission of greenhouse gases (GHGs). The extent of these effects can vary depending on several factors, including the species of invasive plants, their growth patterns, and the climatic conditions prevailing in the wetland. Understanding the global effects of plant invasion on the emission of methane (CH4) and nitrous oxide (N2O) is crucial for the climate-smart management of wetlands. Here, we performed a global meta-analysis of 207 paired case studies that quantified the effect of non-native plant invasion on CH4 and N2O emissions in tropical/sub-tropical (TS) and temperate (TE) wetlands. The average emission rate of CH4 from the TS wetlands increased significantly from 337 to 577 kg CH4 ha-1 yr-1 in areas where native plants had been displaced by invasive plants. Similarly, in TE wetlands, the emission rates increased from 211 to 299 kg CH4 ha-1 yr-1 following the invasion of alien plant species. The increase in CH4 emissions at invaded sites was attributed to the increase in plant biomass, soil organic carbon (SOC), and soil moisture (SM). The effects of plant invasion on N2O emissions differed between TS and TE wetlands in that there was no significant effect in TS wetlands, whereas the N2O emissions reduced in TE wetlands. This difference in N2O emissions between climate zones was attributed to the depletion of NH4+ and NO3- in soils and the lower soil temperature in temperate regions. Overall, plant invasion increased the global net CH4 emissions from natural wetlands by 10.54 Tg CH4 yr-1. However, there were variations in CH4 emissions across different climatic zones, indicated by a net increase in CH4 emissions, of 9.97 and 0.57 Tg CH4 yr-1 in TS and TE wetlands, respectively. These findings highlight that plant invasion not only strongly stimulates the emission of CH4 from TS wetlands, but also suppresses N2O emissions from TE wetlands. These novel insights immensely improve our current understanding of the effects of climatic zones on biogeochemical controlling factors that influence the production of greenhouse gases (GHGs) from wetlands following plant invasion. By analyzing the specific mechanisms by which invasive plants affect GHG emissions in different climatic zones, effective strategies can be devised to reduce GHG emissions and preserve wetland ecosystems.</p
The effect of two speech and language approaches on speech problems in people with Parkinson's disease: the PD COMM RCT
Get PDFSpeech impairments are common with Parkinson's disease (reported prevalence 68%), increasing conversational demands, reliance on family and social withdrawal. The PD COMM trial compared the clinical and cost-effectiveness of two speech and language therapy approaches: Lee Silverman Voice Treatment LOUD and National Health Service speech and language therapy for the treatment of speech or voice problems in people with Parkinson's disease to no speech and language therapy (control) and against each other. PD COMM is a phase III, multicentre, three-arm, unblinded, randomised controlled trial. Participants were randomised in a 1 : 1 : 1 ratio to control, National Health Service speech and language therapy or Lee Silverman Voice Treatment LOUD via a central computer-generated programme, using a minimisation procedure with a random element, to ensure allocation concealment. Mixed-methods process and health economic evaluations were conducted. United Kingdom outpatient and home settings. People with idiopathic Parkinson's disease, with self-reported or carer-reported speech or voice problems. We excluded people with dementia, laryngeal pathology and those within 24 months of previous speech and language therapy. The Lee Silverman Voice Treatment LOUD intervention included maximum effort drills and high-effort speech production tasks delivered over four 50-minute therapist-led personalised sessions per week, for 4 weeks with prescribed daily home practice. National Health Service speech and language therapy content and dosage reflected local non-Lee Silverman Voice Treatment speech and language therapy practices, usually 1 hour, once weekly, for 6 weeks. Trained, experienced speech and language therapists or assistants provided interventions. The control was no speech and language therapy until the trial was completed. Primary outcome: Voice Handicap Index total score at 3 months. Secondary outcomes: Voice Handicap Index subscales, Parkinson's Disease Questionnaire-39; Questionnaire on Acquired Speech Disorders; EuroQol-5D-5L; ICEpop Capabilities Measure for Older Adults; Parkinson's Disease Questionnaire - Carers; resource utilisation; and adverse events. Assessments were completed pre-randomisation and at 3, 6 and 12 months post randomisation. Three hundred and eighty-eight participants were randomised to Lee Silverman Voice Treatment LOUD ( = 130), National Health Service speech and language therapy ( = 129) and control ( = 129). The impact of voice problems at 3 months after randomisation was lower for Lee Silverman Voice Treatment LOUD participants than control [-8.0 (99% confidence interval: -13.3, -2.6); = 0.001]. There was no evidence of improvement for those with access to National Health Service speech and language therapy when compared to control [1.7 (99% confidence interval: -3.8, 7.1); = 0.4]. Participants randomised to Lee Silverman Voice Treatment LOUD reported a lower impact of their voice problems than participants randomised to National Health Service speech and language therapy [99% confidence interval: -9.6 (-14.9, -4.4);
Phase Limitations of Multipliers for Nonlinearities With Monotone Bounds
Get PDFWe consider Lurye systems, whose nonlinear operator is characterized by a nonlinearity that is bounded above and below by monotone functions. Absolute stability can be established using a subclass of the O'Shea-Zames-Falb multipliers. We develop phase conditions for both continuous-time and discrete-time systems under which there can be no such suitable multiplier for the transfer function of a given plant. In discrete time the condition can be tested via a linear program, while in continuous time it can be tested efficiently by exploiting convex structure. Results provide useful insight into the dynamic behaviour of such systems and we illustrate the phase limitations with examples from the literature