Using LiDAR to assess the effect of fire and floods on upland peat bogs, Waterfall Gully, Mount Lofty Ranges, South Australia

A flood exceeding the 100 year average recurrence interval in November 2005 led to the failure of an upland peat bog in Waterfall Gully. The area is prone to severe bushfire and flood events and the control dam at the base of First Falls was filled with sediment sourced from Wilson Bog. A resistant quartzite bar at Fourth Falls has formed a natural constriction point against which burnt logs and debris have collected following previous fire events forming a natural dam resulting in sediment/peat accumulation upstream. The failure of the bog was inevitable as the vegetative material in the log-jam progressively weakened and rotted. Intense flooding triggered the failure but it was augmented by the build up of a critical mass of sediment upstream of the restriction point. The downstream force of the flood waters and the weight of the saturated bog sediments was enough to overcome the basal frictional forces resulting in slumping and headward erosion. LiDAR data clearly shows an erosion channel scoured out by the flood. Approximately 5000 m3 of sediment (-10,100 tonnes) was washed downstream. LiDAR coupled with a tri-spectral scanner has the capacity to identify other upland peat bogs due to their high NDVI value and assess their stability on steep slopes or narrow valleys. Fire is another risk to the stability of these bogs as it has the potential to remove binding vegetation and expose unconsolidated sediments to erosion during subsequent rain events. Groundsurface and vegetation surface DEM\u27s generated from LiDAR combined with NDVI maps derived from a tri-spectral scanner provide an ideal tool to monitor and assess the risk of slumping in other upland peat bogs

Evaluating techniques for mapping island vegetation from unmanned aerial vehicle (UAV) images: Pixel classification, visual interpretation and machine learning approaches

We evaluate three approaches to mapping vegetation using images collected by an unmanned aerial vehicle (UAV) to monitor rehabilitation activities in the Five Islands Nature Reserve, Wollongong (Australia). Between April 2017 and July 2018, four aerial surveys of Big Island were undertaken to map changes to island vegetation following helicopter herbicide sprays to eradicate weeds, including the creeper Coastal Morning Glory (Ipomoea cairica) and Kikuyu Grass (Cenchrus clandestinus). The spraying was followed by a large scale planting campaign to introduce native plants, such as tussocks of Spiny-headed Mat-rush (Lomandra longifolia). Three approaches to mapping vegetation were evaluated, including: (i) a pixel-based image classification algorithm applied to the composite spectral wavebands of the images collected, (ii) manual digitisation of vegetation directly from images based on visual interpretation, and (iii) the application of a machine learning algorithm, LeNet, based on a deep learning convolutional neural network (CNN) for detecting planted Lomandra tussocks. The uncertainty of each approach was assessed via comparison against an independently collected field dataset. Each of the vegetation mapping approaches had a comparable accuracy; for a selected weed management and planting area, the overall accuracies were 82 %, 91 % and 85 % respectively for the pixel based image classification, the visual interpretation / digitisation and the CNN machine learning algorithm. At the scale of the whole island, statistically significant differences in the performance of the three approaches to mapping Lomandra plants were detected via ANOVA. The manual digitisation took a longer time to perform than others. The three approaches resulted in markedly different vegetation maps characterised by different digital data formats, which offered fundamentally different types of information on vegetation character. We draw attention to the need to consider how different digital map products will be used for vegetation management (e.g. monitoring the health individual species or a broader profile of the community). Where individual plants are to be monitored over time, a feature-based approach that represents plants as vector points is appropriate. The CNN approach emerged as a promising technique in this regard as it leveraged spatial information from the UAV images within the architecture of the learning framework by enforcing a local connectivity pattern between neurons of adjacent layers to incorporate the spatial relationships between features that comprised the shape of the Lomandra tussocks detected

Evaluating techniques for mapping island vegetation from unmanned aerial vehicle (UAV) images: Pixel classification, visual interpretation and machine learning approaches

We evaluate three approaches to mapping vegetation using images collected by an unmanned aerial vehicle (UAV) to monitor rehabilitation activities in the Five Islands Nature Reserve, Wollongong (Australia). Between April 2017 and July 2018, four aerial surveys of Big Island were undertaken to map changes to island vegetation following helicopter herbicide sprays to eradicate weeds, including the creeper Coastal Morning Glory (Ipomoea cairica) and Kikuyu Grass (Cenchrus clandestinus). The spraying was followed by a large scale planting campaign to introduce native plants, such as tussocks of Spiny-headed Mat-rush (Lomandra longifolia). Three approaches to mapping vegetation were evaluated, including: (i) a pixel-based image classification algorithm applied to the composite spectral wavebands of the images collected, (ii) manual digitisation of vegetation directly from images based on visual interpretation, and (iii) the application of a machine learning algorithm, LeNet, based on a deep learning convolutional neural network (CNN) for detecting planted Lomandra tussocks. The uncertainty of each approach was assessed via comparison against an independently collected field dataset. Each of the vegetation mapping approaches had a comparable accuracy; for a selected weed management and planting area, the overall accuracies were 82 %, 91 % and 85 % respectively for the pixel based image classification, the visual interpretation / digitisation and the CNN machine learning algorithm. At the scale of the whole island, statistically significant differences in the performance of the three approaches to mapping Lomandra plants were detected via ANOVA. The manual digitisation took a longer time to perform than others. The three approaches resulted in markedly different vegetation maps characterised by different digital data formats, which offered fundamentally different types of information on vegetation character. We draw attention to the need to consider how different digital map products will be used for vegetation management (e.g. monitoring the health individual species or a broader profile of the community). Where individual plants are to be monitored over time, a feature-based approach that represents plants as vector points is appropriate. The CNN approach emerged as a promising technique in this regard as it leveraged spatial information from the UAV images within the architecture of the learning framework by enforcing a local connectivity pattern between neurons of adjacent layers to incorporate the spatial relationships between features that comprised the shape of the Lomandra tussocks detected

Women with gestational diabetes in Vietnam: a qualitative study to determine attitudes and health behaviours

Extent: 10p.Background: Diabetes is increasing in prevalence globally, notably amongst populations from low- and middle- income countries. Gestational Diabetes Mellitus(GDM), a precursor for type 2 diabetes, is increasing in line with this trend. Few studies have considered the personal and social effects of GDM on women living in low and middle-income countries. The aim of this study was determine attitudes and health behaviours of pregnant women with GDM in Vietnam. Methods: This was a qualitative study using focus group methodology conducted in Ho Chi Minh City. Pregnant women, aged over 18 years, with GDM were eligible to participate. Women were purposely sampled to obtain a range of gestational ages and severity of disease. They were invited to attend a 1-hour focus group. Questions were semi structured around six themes. Focus groups were recorded, transcribed, translated and cross-referenced. Non-verbal and group interactions were recorded. Thematic analysis was performed using a theoretical framework approach. Results: From December 2010 to February 2011, four focus groups were conducted involving 34 women. Median age was 31.5 years (range 23 to 44), median BMI 21.8 kg/m2. Women felt confusion, anxiety and guilt about GDM. Many perceived their baby to be at increased risk of death. Advice to reduce dietary starch was confusing. Women reported being ‘hungry’ or ‘starving’ most of the time, unaware of appropriate food substitutions. They were concerned about transmission of GDM through breast milk. Several women planned not to breastfeed. All felt they needed more information. Current sources of information included friends, magazines, a health phone line or the Internet. Women felt small group sessions and information leaflets could benefit them. Conclusions: This study highlights the need for culturally appropriate clinical education and health promotion activities for women with GDM in Vietnam.Jane E Hirst, Thach Son Tran, My An Thi Do, Forsyth Rowena, Jonathan M Morris and Heather E Jeffer

Identification of a novel functional deletion variant in the 5'-UTR of the DJ-1 gene

<p>Abstract</p> <p>Background</p> <p>DJ-1 forms part of the neuronal cellular defence mechanism against oxidative insults, due to its ability to undergo self-oxidation. Oxidative stress has been implicated in the pathogenesis of central nervous system damage in different neurodegenerative disorders including Alzheimer's disease and Parkinson's disease (PD). Various mutations in the <it>DJ-1 </it>(<it>PARK7</it>) gene have been shown to cause the autosomal recessive form of PD. In the present study South African PD patients were screened for mutations in <it>DJ-1 </it>and we aimed to investigate the functional significance of a novel 16 bp deletion variant identified in one patient.</p> <p>Methods</p> <p>The possible effect of the deletion on promoter activity was investigated using a Dual-Luciferase Reporter assay. The <it>DJ-1 </it>5'-UTR region containing the sequence flanking the 16 bp deletion was cloned into a pGL4.10-Basic luciferase-reporter vector and transfected into HEK293 and BE(2)-M17 neuroblastoma cells. Promoter activity under hydrogen peroxide-induced oxidative stress conditions was also investigated. Computational (<it>in silico</it>) <it>cis</it>-regulatory analysis of <it>DJ-1 </it>promoter sequence was performed using the transcription factor-binding site database, TRANSFAC via the PATCH™ and rVISTA platforms.</p> <p>Results</p> <p>A novel 16 bp deletion variant (g.-6_+10del) was identified in <it>DJ-1 </it>which spans the transcription start site and is situated 93 bp 3' from a Sp1 site. The deletion caused a reduction in luciferase activity of approximately 47% in HEK293 cells and 60% in BE(2)-M17 cells compared to the wild-type (<it>P </it>< 0.0001), indicating the importance of the 16 bp sequence in transcription regulation. The activity of both constructs was up-regulated during oxidative stress. Bioinformatic analysis revealed putative binding sites for three transcription factors AhR, ARNT, HIF-1 within the 16 bp sequence. The frequency of the g.-6_+10del variant was determined to be 0.7% in South African PD patients (2 heterozygotes in 148 individuals).</p> <p>Conclusion</p> <p>This is the first report of a functional <it>DJ-1 </it>promoter variant, which has the potential to influence transcript stability or translation efficiency. Further work is necessary to determine the extent to which the g.-6_+10del variant affects the normal function of the <it>DJ-1 </it>promoter and whether this variant confers a risk for PD.</p

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

The adverse impact of COVID-19 pandemic on cardiovascular disease prevention and management in England, Scotland and Wales: A population-scale analysis of trends in medication data

Objectives To estimate the impact of the COVID-19 pandemic on cardiovascular disease (CVD) and CVD management using routinely collected medication data as a proxy. Design Descriptive and interrupted time series analysis using anonymised individual-level population-scale data for 1.32 billion records of dispensed CVD medications across 15.8 million individuals in England, Scotland and Wales. Setting Community dispensed CVD medications with 100% coverage from England, Scotland and Wales, plus primary care prescribed CVD medications from England (including 98% English general practices). Participants 15.8 million individuals aged 18+ years alive on 1 st April 2018 dispensed at least one CVD medicine in a year from England, Scotland and Wales. Main outcome measures Monthly counts, percent annual change (1 st April 2018 to 31 st July 2021) and annual rates (1 st March 2018 to 28 th February 2021) of medicines dispensed by CVD/ CVD risk factor; prevalent and incident use. Results Year-on-year change in dispensed CVD medicines by month were observed, with notable uplifts ahead of the first (11.8% higher in March 2020) but not subsequent national lockdowns. Using hypertension as one example of the indirect impact of the pandemic, we observed 491,203 fewer individuals initiated antihypertensive treatment across England, Scotland and Wales during the period March 2020 to end May 2021 than would have been expected compared to 2019. We estimated that this missed antihypertension treatment could result in 13,659 additional CVD events should individuals remain untreated, including 2,281 additional myocardial infarctions (MIs) and 3,474 additional strokes. Incident use of lipid-lowering medicines decreased by an average 14,793 per month in early 2021 compared with the equivalent months prior to the pandemic in 2019. In contrast, the use of incident medicines to treat type-2 diabetes (T2DM) increased by approximately 1,642 patients per month. Conclusions Management of key CVD risk factors as proxied by incident use of CVD medicines has not returned to pre-pandemic levels in the UK. Novel methods to identify and treat individuals who have missed treatment are urgently required to avoid large numbers of additional future CVD events, further adding indirect cost of the COVID-19 pandemic

COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records

BACKGROUND: Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. METHODS: In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. FINDINGS: Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. INTERPRETATION: Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. FUNDING: British Heart Foundation Data Science Centre, led by Health Data Research UK

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society