207 research outputs found

    The impact of satellite sensor viewing geometry on time-series analysis of volcanic emissions

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    Time-series analysis techniques are being increasingly used to process satellite observations of volcanic gas emissions and heat flux, with the aim of identifying cyclic behaviour that could inform hazard assessment or elucidate volcanic processes. However, it can be difficult to distinguish cyclic variations due to geophysical processes from those that are artefacts of the observation technique. Here, we conduct a comprehensive investigation into the origin of cyclicity in volcanic observations by analysing daily, global satellite measurements of volcanic SO2 loading by the Ozone Monitoring Instrument (OMI) and thermal infrared anomalies detected by the Moderate Resolution Imaging Spectroradiometer (MODIS). We use a fast Fourier Transform (FFT) multi-taper method (MTM) to analyse multiple phases of activity at 32 target volcanoes, utilising measurements obtained from three NASA satellite instruments (Aura – OMI, Aqua – MODIS and Terra – MODIS), and identify a common cycle (period of ~ 2.3 days), which is not considered to be of volcanic origin. Based on the presence of this cycle in multiple satellite datasets, we attribute it to variations in viewing angle during the 16-day orbit repeat cycle of sun-synchronous satellites maintained in Low Earth Orbit (LEO). A 5-point averaging correction procedure is tested on satellite observations from Kilauea volcano, Hawaii, and is found to reduce the impact of higher frequency cycles and reveal the presence of longer-period geophysical signals. In addition to the identification of a signal common to different measurement techniques, an underlying cyclical pattern was found in the OMI SO2 observations (periods of ~ 7.9 and 3.2 days) generated by the OMI Row Anomaly (ORA). We conclude that identification of the presence and magnitude of non-geophysical cyclic behaviour, which can suppress natural cycles in time-series data, and implementation of appropriate corrections, is crucial for accurate interpretation of satellite observations. The use of data averaging to suppress non-geophysical cycles imposes limits on the length of natural cycles that can be confidently identified in moderate resolution satellite observations from polar-orbiting spacecraft

    Enhancing the experience of carers in the chemotherapy outpatient setting: an exploratory randomised controlled trial to test impact, acceptability and feasibility of a complex intervention co-designed by carers and staff

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    PurposeSupporting someone through chemotherapy can be emotionally and physically demanding. However, research has yet to establish the type of support carers require or the best way to provide this. This study tested the feasibility and acceptability of a complex intervention for carers that was co-designed by staff and carers of patients starting chemotherapy.MethodsForty-seven carers were recruited, randomised between the intervention (n?=?24) and control (n?=?23) groups. A questionnaire was completed pre- and post-intervention measuring knowledge of chemotherapy and its side effects, experience of care, satisfaction with outpatient services, coping and emotional wellbeing. The intervention process was evaluated by carers and healthcare professionals (HCPs) in focus groups.ResultsRecruitment to the study was unproblematic and attrition from it was low, suggesting the intervention and study processes were acceptable to patients and carers. Carers in receipt of the ‘Take Care’ intervention reported statistically significantly better understanding of symptoms and side effects and their information needs being more frequently met than carers in the control. Confidence in coping improved between baseline and follow-up for the intervention group and declined for the control although differences were insufficient to achieve statistical significance. There was no significant difference between the two groups’ emotional wellbeing. HCP and carer focus groups confirmed the feasibility and acceptability of the intervention.ConclusionsThe ‘Take Care’ intervention proved acceptable to carers and HCPs and demonstrates considerable promise and utility in practice. Study findings support the conduct of a fully powered RCT to determine the intervention’s effectiveness and cost-effectiveness

    Step into My Mind Palace:Exploration of a Collaborative Paragogy Tool in VR

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    Virtual Reality (VR) can mediate remote collaborative learning and can support pedagogical processes like paragogy. Within education, methods such as spaced repetition and memory palaces exist to support the cognitive process of remembering. We identify an opportunity to enhance learner-led collaborative paragogy involving these methods through immersive VR experiences. We present CleVR, a VR-mediated collaboration-based system that supports the memory palace and spaced repetition techniques. As an exploratory study, we aim to identify the applicability, viability and user perception for such a system combining these two techniques in VR. CleVR is a novel implementation which provides a location-driven metaphor to populate and present multiple resources related to a topic for peer-led exploration. We discuss the design and provide a prototype implementation of CleVR. We conducted two studies, a targeted expert user review and a broader proof of concept survey. The results of the studies show interesting outcomes, with the system described as ‘engaging’, ‘useful’ and ‘fun’. Our findings provide insights to the potential of using Virtual Reality Learning Environments (VRLE) geared towards collaborative learner-led activities

    Emerging implications of policies on malaria treatment: genetic changes in the Pfmdr-1 gene affecting susceptibility to artemether-lumefantrine and artesunate-amodiaquine in Africa.

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    Artemether-lumefantrine (AL) and artesunate-amodiaquine (AS-AQ) are the most commonly used artemisinin-based combination therapies (ACT) for treatment of Plasmodium falciparum in Africa. Both treatments remain efficacious, but single nucleotide polymorphisms (SNPs) in the Plasmodium falciparum multidrug resistance 1 (Pfmdr1) gene may compromise sensitivity. AL and AS-AQ exert opposing selective pressures: parasites with genotype 86Y, Y184 and 1246Y are partially resistant to AS-AQ treatment, while N86, 184 F and D1246 are favoured by AL treatment. Through a systematic review, we identified 397 surveys measuring the prevalence of Pfmdr1 polymorphisms at positions 86 184 or 1246 in 30 countries in Africa. Temporal trends in SNP frequencies after introduction of AL or AS-AQ as first-line treatment were analysed in 32 locations, and selection coefficients estimated. We examined associations between antimalarial policies, consumption, transmission intensity and rate of SNP selection. 1246Y frequency decreased on average more rapidly in locations where national policy recommended AL (median selection coefficient(s) of -0.083), compared with policies of AS-AQ or both AL and AS-AQ (median s=-0.035 and 0.021, p<0.001 respectively). 86Y frequency declined markedly after ACT policy introduction, with a borderline significant trend for a more rapid decline in countries with AL policies (p=0.055). However, these trends could also be explained by a difference in initial SNP frequencies at the time of ACT introduction. There were non-significant trends for faster selection of N86 and D1246 in areas with higher AL consumption and no trend with transmission intensity. Recorded consumption of AS-AQ was low in the locations and times Pfmdr1 data were collected. SNP trends in countries with AL policies suggest a broad increase in sensitivity of parasites to AS-AQ, by 7-10 years after AL introduction. Observed rates of selection have implications for planning strategies to cycle drugs or use multiple first-line therapies to maintain drug efficacy

    PAK4 regulates stemness and progression in endocrine resistant ER-positive metastatic breast cancer

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    Despite the effectiveness of endocrine therapies to treat estrogen receptor-positive (ER+) breast tumours, two thirds of patients will eventually relapse due to de novo or acquired resistance to these agents. Cancer Stem-like Cells (CSCs), a rare cell population within the tumour, accumulate after anti-estrogen treatments and are likely to contribute to their failure. Here we studied the role of p21-activated kinase 4 (PAK4) as a promising target to overcome endocrine resistance and disease progression in ER+ breast cancers. PAK4 predicts for resistance to tamoxifen and poor prognosis in 2 independent cohorts of ER+ tumours. We observed that PAK4 strongly correlates with CSC activity in metastatic patient-derived samples irrespective of breast cancer subtype. However, PAK4-driven mammosphere-forming CSC activity increases alongside progression only in ER+ metastatic samples. PAK4 activity increases in ER+ models during acquired resistance to endocrine therapies. Targeting PAK4 with either CRT PAKi, a small molecule inhibitor of PAK4, or with specific siRNAs abrogates CSC activity/self-renewal in clinical samples and endocrine-resistant cells. Together, our findings establish that PAK4 regulates stemness during disease progression and that its inhibition reverses endocrine resistance in ER+ breast cancers

    Population sensitivity of acute flaccid paralysis and environmental surveillance for serotype 1 poliovirus in Pakistan: an observational study.

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    BACKGROUND: To support poliomyelitis eradication in Pakistan, environmental surveillance (ES) of wastewater has been expanded alongside surveillance for acute flaccid paralysis (AFP). ES is a relatively new method of surveillance, and the population sensitivity of detecting poliovirus within endemic settings requires estimation. METHODS: Data for wild serotype 1 poliovirus from AFP and ES from January 2011 to September 2015 from 14 districts in Pakistan were analysed using a multi-state model framework. This framework was used to estimate the sensitivity of poliovirus detection from each surveillance source and parameters such as the duration of infection within a community. RESULTS: The location and timing of poliomyelitis cases showed spatial and temporal variability. The sensitivity of AFP surveillance to detect serotype 1 poliovirus infection in a district and its neighbours per month was on average 30.0% (95% CI 24.8-35.8) and increased with the incidence of poliomyelitis cases. The average population sensitivity of a single environmental sample was 59.4% (95% CI 55.4-63.0), with significant variation in site-specific estimates (median varied from 33.3-79.2%). The combined population sensitivity of environmental and AFP surveillance in a given month was on average 98.1% (95% CI 97.2-98.7), assuming four samples per month for each site. CONCLUSIONS: ES can be a highly sensitive supplement to AFP surveillance in areas with converging sewage systems. As ES for poliovirus is expanded, it will be important to identify factors associated with variation in site sensitivity, leading to improved site selection and surveillance system performance

    Evaluating the performance of malaria genomics for inferring changes in transmission intensity using transmission modelling

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    AbstractAdvances in genetic sequencing and accompanying methodological approaches have resulted in pathogen genetics being used in the control of infectious diseases. To utilise these methodologies for malaria we first need to extend the methods to capture the complex interactions between parasites, human and vector hosts, and environment. Here we develop an individual-based transmission model to simulate malaria parasite genetics parameterised using estimated relationships between complexity of infection and age from 5 regions in Uganda and Kenya. We predict that cotransmission and superinfection contribute equally to within-host parasite genetic diversity at 11.5% PCR prevalence, above which superinfections dominate. Finally, we characterise the predictive power of six metrics of parasite genetics for detecting changes in transmission intensity, before grouping them in an ensemble statistical model. The best performing model successfully predicted malaria prevalence with mean absolute error of 0.055, suggesting genetic tools could be used for monitoring the impact of malaria interventions.</jats:p

    The effect of polyploidy and hybridization on the evolution of floral colour in Nicotiana (Solanaceae)

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    Background and Aims: We investigate whether changes in floral colour accompany polyploid and homoploid hybridisation, important processes in angiosperm evolution. Potentially, changes in floral colour can facilitate speciation through pollinator shifts. Methods: We examined spectral reflectance of corolla tissue from 60 Nicotiana (Solanaceae) accessions (41 taxa) based on spectral shape (corresponding to pigmentation) as well as bee and hummingbird colour perception to assess patterns of floral colour evolution. We compared polyploid and homoploid hybrid spectra to those of their progenitors to evaluate whether hybridisation has resulted in floral colour shifts. Key Results: Floral colour categories in Nicotiana seem to have arisen multiple times independently during the evolution of the genus. Polyploid and homoploid hybrids can display a floral colour: 1) intermediate between progenitors, 2) like one or other progenitor, or 3) a transgressive or divergent colour not present in either progenitor. Conclusions: Floral colour evolution in Nicotiana is weakly constrained by phylogeny, but colour shifts occur and are sometimes associated with allopolyploid or homoploid speciation. Transgressive floral colour in N. tabacum has arisen by inheritance of anthocyanin pigmentation from its paternal progenitor while having a plastid phenotype like its maternal progenitor. Potentially, floral colour evolution has been driven by, or resulted in, pollinator shifts

    Associations of Early Childhood Manganese and Lead Coexposure with Neurodevelopment

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    Background: Most toxicologic studies focus on a single agent, although this does not reflect real-world scenarios in which humans are exposed to multiple chemicals

    Neurodegeneration and Epilepsy in a Zebrafish Model of CLN3 Disease (Batten Disease)

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    The neuronal ceroid lipofuscinoses are a group of lysosomal storage disorders that comprise the most common, genetically heterogeneous, fatal neurodegenerative disorders of children. They are characterised by childhood onset, visual failure, epileptic seizures, psychomotor retardation and dementia. CLN3 disease, also known as Batten disease, is caused by autosomal recessive mutations in the CLN3 gene, 80–85% of which are a ~1 kb deletion. Currently no treatments exist, and after much suffering, the disease inevitably results in premature death. The aim of this study was to generate a zebrafish model of CLN3 disease using antisense morpholino injection, and characterise the pathological and functional consequences of Cln3 deficiency, thereby providing a tool for future drug discovery. The model was shown to faithfully recapitulate the pathological signs of CLN3 disease, including reduced survival, neuronal loss, retinopathy, axonopathy, loss of motor function, lysosomal storage of subunit c of mitochondrial ATP synthase, and epileptic seizures, albeit with an earlier onset and faster progression than the human disease. Our study provides proof of principle that the advantages of the zebrafish over other model systems can be utilised to further our understanding of the pathogenesis of CLN3 disease and accelerate drug discovery
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