Associations of specific-age and decade recall body mass index trajectories with obesity-related cancer.

From Europe PMC via Jisc Publications RouterHistory: ppub 2021-05-01, epub 2021-05-05Publication status: PublishedFunder: Manchester Biomedical Research Centre; Grant(s): IS-BRC-1215-20007BackgroundExcess body fatness, commonly approximated by a one-off determination of body mass index (BMI), is associated with increased risk of at least 13 cancers. Modelling of longitudinal BMI data may be more informative for incident cancer associations, e.g. using latent class trajectory modelling (LCTM) may offer advantages in capturing changes in patterns with time. Here, we evaluated the variation in cancer risk with LCTMs using specific age recall versus decade recall BMI.MethodsWe obtained BMI profiles for participants from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We developed gender-specific LCTMs using recall data from specific ages 20 and 50 years (72,513 M; 74,837 W); decade data from 30s to 70s (42,113 M; 47,352 W) and a combination of both (74,106 M, 76,245 W). Using an established methodological framework, we tested 1:7 classes for linear, quadratic, cubic and natural spline shapes, and modelled associations for obesity-related cancer (ORC) incidence using LCTM class membership.ResultsDifferent models were selected depending on the data type used. In specific age recall trajectories, only the two heaviest classes were associated with increased risk of ORC. For the decade recall data, the shapes appeared skewed by outliers in the heavier classes but an increase in ORC risk was observed. In the combined models, at older ages the BMI values were more extreme.ConclusionsSpecific age recall models supported the existing literature changes in BMI over time are associated with increased ORC risk. Modelling of decade recall data might yield spurious associations

Utilising eDNA methods and interactive data dashboards for managing sustainable drinking water

Generating rapid, easy-to-interpret community data for drinking reservoirs as a means of tackling water quality management is of increasing demand within the water industry. Taste and odour (T&O) is one of many increasing concerns to water companies worldwide, incurring huge costs as customer complaints accumulate and additional treatment and resource management are required. However, there remains a two-fold issue in addressing T&O management: firstly, predicting the initial onset of a T&O event relies on a highly complex understanding of environmental considerations and their interaction with T&O-related taxa, and secondly, there remains a lag between the notification of a T&O event and the resolution of the issue by reservoir management staff. This is partly due to slow, low-resolution methods of detecting and reliably identifying problem taxa in samples. These methods are unable to provide information on the huge plethora of taxa related to T&O metabolite production and often cannot provide data in a timely enough manner for an opportune management response. This means the water industry is often forced to use a reactive, rather than proactive, approach to water quality monitoring. Here, we present methods for implementing a high-throughput sequencing approach to monitoring drinking reservoirs for water quality and improving the sustainability of water supplies, as well as methods for presenting these data on easy-to-interpret data dashboards that can be updated rapidly as new data are generated. Our methods and dashboarding approaches are currently being trialled and tested within the UK water industry, and so here, we show anonymised examples of those data presentations. We propose that these methods can greatly aid reservoir management teams in their approach to T&O monitoring and can be used to implore more sustainable management pipelines, safeguarding future water sources

Inflammation drives thrombosis after Salmonella infection via CLEC-2 on platelets

Thrombosis is a common, life-threatening consequence of systemic infection; however, the underlying mechanisms that drive the formation of infection-associated thrombi are poorly understood. Here, using a mouse model of systemic Salmonella Typhimurium infection, we determined that inflammation in tissues triggers thrombosis within vessels via ligation of C-type lectin-like receptor-2 (CLEC-2) on platelets by podoplanin exposed to the vasculature following breaching of the vessel wall. During infection, mice developed thrombi that persisted for weeks within the liver. Bacteria triggered but did not maintain this process, as thrombosis peaked at times when bacteremia was absent and bacteria in tissues were reduced by more than 90% from their peak levels. Thrombus development was triggered by an innate, TLR4-dependent inflammatory cascade that was independent of classical glycoprotein VI-mediated (GPVI-mediated) platelet activation. After infection, IFN-ã release enhanced the number of podoplanin-expressing monocytes and Kupffer cells in the hepatic parenchyma and perivascular sites and absence of TLR4, IFN-ã, or depletion of monocytic-lineage cells or CLEC-2 on platelets markedly inhibited the process. Together, our data indicate that infection-driven thrombosis follows local inflammation and upregulation of podoplanin and platelet activation. The identification of this pathway offers potential therapeutic opportunities to control the devastating consequences of infection-driven thrombosis without increasing the risk of bleeding

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Using theories of behaviour to understand transfusion prescribing in three clinical contexts in two countries: Development work for an implementation trial

<p>Abstract</p> <p>Background</p> <p>Blood transfusion is an essential part of healthcare and can improve patient outcomes. However, like most therapies, it is also associated with significant clinical risks. In addition, there is some evidence of overuse. Understanding the potential barriers and enablers to reduced prescribing of blood products will facilitate the selection of intervention components likely to be effective, thereby reducing the number of costly trials evaluating different implementation strategies. Using a theoretical basis to understand behaviours targeted for change will contribute to a 'basic science' relating to determinants of professional behaviour and how these inform the selection of techniques for changing behaviour. However, it is not clear which theories of behaviour are relevant to clinicians' transfusing behaviour. The aim of this study is to use a theoretical domains framework to identify relevant theories, and to use these theories to identify factors that predict the decision to transfuse.</p> <p>Methods</p> <p>The study involves two steps: interview study and questionnaire study. Using a previously identified framework, we will conduct semi-structured interviews with clinicians to elicit their views about which factors are associated with waiting and further monitoring the patient rather than transfusing red blood cells. Interviews will cover the following theoretical domains: knowledge; skills; social/professional role and identity; beliefs about capabilities; beliefs about consequences; motivation and goals; memory, attention, and decision processes; environmental context and resources; social influences; emotion; behavioural regulation; nature of the behaviour. The interviews will take place independently in Canada and the UK and involve two groups of physicians in each country (UK: adult and neonatal intensive care physicians; Canada: intensive care physicians and orthopaedic surgeons). We will: analyse interview transcript content to select relevant theoretical domains; use consensus processes to map these domains on to theories of behaviour; develop questionnaires based on these theories; and mail them to each group of physicians in the two countries. From our previous work, it is likely that the theories will include: theory of planned behaviour, social cognitive theory and the evidence-based strategy, implementation intention. The questionnaire data will measure predictor variables (theoretical constructs) and outcome variables (intention and clinical decision), and will be analysed using multiple regression analysis. We aim to achieve 150 respondents in each of the four groups for each postal survey.</p

The management of desmoid tumours: A joint global consensus-based guideline approach for adult and paediatric patients

Abstract Desmoid tumor (DT; other synonymously used terms: Desmoid-type fibromatosis, aggressive fibromatosis) is a rare and locally aggressive monoclonal, fibroblastic proliferation characterised by a variable and often unpredictable clinical course. Previously surgery was the standard primary treatment modality; however, in recent years a paradigm shift towards a more conservative management has been introduced and an effort to harmonise the strategy amongst clinicians has been made. We present herein an evidence-based, joint global consensus guideline approach to the management of this disease focussing on: molecular genetics, indications for an active treatment, and available systemic therapeutic options. This paper follows a one-day consensus meeting held in Milan, Italy, in June 2018 under the auspices of the European Reference Network for rare solid adult cancers, EURACAN, the European Organisation for Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group (STBSG) as well as Sarcoma Patients EuroNet (SPAEN) and The Desmoid tumour Research Foundation (DTRF). The meeting brought together over 50 adult and pediatric sarcoma experts from different disciplines, patients and patient advocates from Europe, North America and Japan