P193 USEFUL I: musculoskeletal ultrasound to identify patients with lupus arthritis with better response to therapy

Background In SLE, musculoskeletal manifestations have an impact on quality of life, disability and clinical trial outcomes, but are harder to assess than in RA and PsA. We previously showed that joint swelling lacks sensitivity, specificity and responsiveness compared to ultrasound. USEFUL was a multicentre longitudinal study to determine clinical features predicting ultrasound synovitis and whether patients with ultrasound synovitis respond better to therapy. Methods SLE patients were recruited if the referring physician deemed they had inflammatory pain warranting treatment. Swollen joints were not required. At baseline, physicians recorded the features that led them to diagnose inflammatory pain and features of concurrent fibromyalgia and osteoarthritis. Stable doses of prednisolone (≤5 mg/day), antimalarials or immunosuppressants were allowed. Participants received depomedrone 120 mg IM then were assessed at 0, 2 and 6 weeks for 66/68 swollen and tender joint counts, BILAG-2004, SLEDAI-2K, physician global and MSK-VAS, inflammatory markers, patient pain and disease activity-VAS, HAQ-DI, LupusQoL, ultrasound of hands and wrists (blinded to patient and clinical assessor). An internal pilot determined the primary endpoint: EMS-VAS at 2 weeks (adjusted for baseline) between patients with ultrasound-synovitis vs. normal ultrasound at baseline. Sensitivity analyses adjusted for prednisolone and immunosuppressants. Results 122/133 patients recruited completed all visits. There was significant disagreement between clinical examination and ultrasound. 78/133 had ultrasound synovitis; 68% of these had ≥1 swollen joint. Of 66/133 patients with ≥ 1 swollen joint, 20% had normal ultrasound. Ultrasound-synovitis was more likely with joint swelling, a symmetrical small joint distribution and active serology. Physician-determined EMS, other lupus features or prior response to therapy were not associated. Fibromyalgia or osteoarthritis did not reduce the probability of ultrasound synovitis. In the full analysis set (n=133) there was no difference in EMS VAS at 2 weeks according to ultrasound synovial status as baseline (difference -8 mm, 95% CI -19, 4 mm, p=0.178). 32 patients had fibromyalgia. After excluding these patients, we found a statistically and clinically significantly better clinical response to depomedrone in patients with ultrasound-synovitis at baseline (baseline-adjusted EMS VAS at 2 weeks -12 mm, 95% CI -24, 0 mm, p=0.049). This difference was greater in the treatment-adjusted sensitivity analysis (-12.8 (95% CI -22, -3 mm), p=0.007) and the per-protocol-adjusted sensitivity analysis (-14.8 mm (95% CI -20.8, -8.8 mm), p<0.001). Patient with ultrasound synovitis had higher rates of improvement in the musculoskeletal BILAG-2004 (56% vs. 26%, p=0.09) and SLEDAI-2K (37% vs. 15%, p=0.03). Conclusions In lupus arthritis distribution and serology, but not other features, help identify ultrasound-synovitis. Ultrasound-synovitis was independent of features of fibromyalgia, but fibromyalgia confounded assessment of response. Excluding fibromyalgia, response to therapy was better in patients with abnormal ultrasound compared to normal. Ultrasound should be used to select patients for therapy and clinical trials, especially when there are inflammatory symptoms without swollen joints

Current progress on removal of recalcitrance coloured particles from anaerobically treated effluent using coagulation–flocculation

The palm oil industry is the most important agro industries in Malaysia and most of the mills adopt anaerobic digestion as their primary treatment for palm oil mill effluent (POME). Due to the public concern, decolourisation of anaerobically treated POME (AnPOME) is becoming a great concern. Presence of recalcitrant-coloured particles hinders biological processes and coagulation–flocculation may able to remove these coloured particles. Several types of inorganic and polymers-based coagulant/flocculant aids for coagulation–flocculation of AnPOME have been reviewed. Researchers are currently interested in using natural coagulant and flocculant aids. Modification of the properties of natural coagulant and flocculant aids enhanced coagulation–flocculation performance. Modelling and optimization of the coagulation–flocculation process have also been reviewed. Chemical sludge has the potential for plant growth that can be evaluated through pot trials and phytotoxicity test

LPS unmasking of Shigella flexneri reveals preferential localisation of tagged outer membrane protease IcsP to septa and new poles

The Shigella flexneri outer membrane (OM) protease IcsP (SopA) is a member of the enterobacterial Omptin family of proteases which cleaves the polarly localised OM protein IcsA that is essential for Shigella virulence. Unlike IcsA however, the specific localisation of IcsP on the cell surface is unknown. To determine the distribution of IcsP, a haemagglutinin (HA) epitope was inserted into the non-essential IcsP OM loop 5 using Splicing by Overlap Extension (SOE) PCR, and IcsP(HA) was characterised. Quantum Dot (QD) immunofluorescence (IF) surface labelling of IcsP(HA) was then undertaken. Quantitative fluorescence analysis of S. flexneri 2a 2457T treated with and without tunicaymcin to deplete lipopolysaccharide (LPS) O antigen (Oag) showed that IcsP(HA) was asymmetrically distributed on the surface of septating and non-septating cells, and that this distribution was masked by LPS Oag in untreated cells. Double QD IF labelling of IcsP(HA) and IcsA showed that IcsP(HA) preferentially localised to the new pole of non-septating cells and to the septum of septating cells. The localisation of IcsP(HA) in a rough LPS S. flexneri 2457T strain (with no Oag) was also investigated and a similar distribution of IcsP(HA) was observed. Complementation of the rough LPS strain with rmlD resulted in restored LPS Oag chain expression and loss of IcsP(HA) detection, providing further support for LPS Oag masking of surface proteins. Our data presents for the first time the distribution for the Omptin OM protease IcsP, relative to IcsA, and the effect of LPS Oag masking on its detection.Elizabeth Ngoc Hoa Tran, Matthew Thomas Doyle, Renato Moron

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

fisheries and tourism social economic and ecological trade offs in coral reef systems

Coastal communities are exerting increasingly more pressure on coral reef ecosystem services in the Anthropocene. Balancing trade-offs between local economic demands, preservation of traditional values, and maintenance of both biodiversity and ecosystem resilience is a challenge for reef managers and resource users. Consistently, growing reef tourism sectors offer more lucrative livelihoods than subsistence and artisanal fisheries at the cost of traditional heritage loss and ecological damage. Using a systematic review of coral reef fishery reconstructions since the 1940s, we show that declining trends in fisheries catch and fish stocks dominate coral reef fisheries globally, due in part to overfishing of schooling and spawning-aggregating fish stocks vulnerable to exploitation. Using a separate systematic review of coral reef tourism studies since 2013, we identify socio-ecological impacts and economic opportunities associated to the industry. Fisheries and tourism have the potential to threaten the ecological stability of coral reefs, resulting in phase shifts toward less productive coral-depleted ecosystem states. We consider whether four common management strategies (unmanaged commons, ecosystem-based management, co-management, and adaptive co-management) fulfil ecological conservation and socioeconomic goals, such as living wage, job security, and maintenance of cultural traditions. Strategies to enforce resource exclusion and withhold traditional resource rights risk social unrest; thus, the coexistence of fisheries and tourism industries is essential. The purpose of this chapter is to assist managers and scientists in their responsibility to devise implementable strategies that protect local community livelihoods and the coral reefs on which they rely

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació