Predicting fracture outcomes from clinical registry data using artificial intelligence supplemented models for evidence-informed treatment (PRAISE) study protocol

BackgroundDistal radius (wrist) fractures are the second most common fracture admitted to hospital. The anatomical pattern of these types of injuries is diverse, with variation in clinical management, guidelines for management remain inconclusive, and the uptake of findings from clinical trials into routine practice limited. Robust predictive modelling, which considers both the characteristics of the fracture and patient, provides the best opportunity to reduce variation in care and improve patient outcomes. This type of data is housed in unstructured data sources with no particular format or schema. The “Predicting fracture outcomes from clinical Registry data using Artificial Intelligence (AI) Supplemented models for Evidence-informed treatment (PRAISE)” study aims to use AI methods on unstructured data to describe the fracture characteristics and test if using this information improves identification of key fracture characteristics and prediction of patient-reported outcome measures and clinical outcomes following wrist fractures compared to prediction models based on standard registry data.Methods and designAdult (16+ years) patients presenting to the emergency department, treated in a short stay unit, or admitted to hospital for >24h for management of a wrist fracture in four Victorian hospitals will be included in this study. The study will use routine registry data from the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR), and electronic medical record (EMR) information (e.g. X-rays, surgical reports, radiology reports, images). A multimodal deep learning fracture reasoning system (DLFRS) will be developed that reasons on EMR information. Machine learning prediction models will test the performance with/without output from the DLFRS.DiscussionThe PRAISE study will establish the use of AI techniques to provide enhanced information about fracture characteristics in people with wrist fractures. Prediction models using AI derived characteristics are expected to provide better prediction of clinical and patient-reported outcomes following distal radius fracture

Portuguese-Brazilian Evidence-Based Guideline on the Management of Hyperglycemia in Type 2 Diabetes Mellitus

Background: In current management of type 2 diabetes (T2DM), cardiovascular and renal prevention have become important targets to be achieved. In this context, a joint panel of four endocrinology societies from Brazil and Portugal was established to develop an evidence-based guideline for treatment of hyperglycemia in T2DM. Methods: MEDLINE (via PubMed) was searched for randomized clinical trials, meta-analyses, and observational studies related to diabetes treatment. When there was insufficient high-quality evidence, expert opinion was sought. Updated positions on treatment of T2DM patients with heart failure (HF), atherosclerotic CV disease (ASCVD), chronic kidney disease (CKD), and patients with no vascular complications were developed. The degree of recommendation and the level of evidence were determined using predefined criteria. Results and conclusions: In non-pregnant adults, the recommended HbA1c target is below 7%. Higher levels are recommended in frail older adults and patients at higher risk of hypoglycemia. Lifestyle modification is recommended at all phases of treatment. Metformin is the first choice when HbA1c is 6.5-7.5%. When HbA1c is 7.5-9.0%, dual therapy with metformin plus an SGLT2i and/or GLP-1RA (first-line antidiabetic agents, AD1) is recommended due to cardiovascular and renal benefits. If an AD1 is unaffordable, other antidiabetic drugs (AD) may be used. Triple or quadruple therapy should be considered when HbA1c remains above target. In patients with clinical or subclinical atherosclerosis, the combination of one AD1 plus metformin is the recommended first-line therapy to reduce cardiovascular events and improve blood glucose control. In stable heart failure with low ejection fraction ( 30 mL/min/1.73 m2, metformin plus an SGLT-2i is recommended to reduce cardiovascular mortality and heart failure hospitalizations and improve blood glucose control. In patients with diabetes-associated chronic kidney disease (CKD) (eGFR 30-60 mL/min/1.73 m2 or eGFR 30-90 mL/min/1.73 m2 with albuminuria > 30 mg/g), the combination of metformin and an SGLT2i is recommended to attenuate loss of renal function, reduce albuminuria and improve blood glucose control. In patients with severe renal failure, insulin-based therapy is recommended to improve blood glucose control. Alternatively, GLP-1RA, DPP4i, gliclazide MR and pioglitazone may be considered to reduce albuminuria. In conclusion, the current evidence supports individualizing anti-hyperglycemic treatment for T2DM.info:eu-repo/semantics/publishedVersio

Formyl Peptide Receptor as a Novel Therapeutic Target for Anxiety-Related Disorders

Formyl peptide receptors (FPR) belong to a family of sensors of the immune system that detect microbe-associated molecules and inform various cellular and sensorial mechanisms to the presence of pathogens in the host. Here we demonstrate that Fpr2/3-deficient mice show a distinct profile of behaviour characterised by reduced anxiety in the marble burying and light-dark box paradigms, increased exploratory behaviour in an open-field, together with superior performance on a novel object recognition test. Pharmacological blockade with a formyl peptide receptor antagonist, Boc2, in wild type mice reproduced most of the behavioural changes observed in the Fpr2/3(-/-) mice, including a significant improvement in novel object discrimination and reduced anxiety in a light/dark shuttle test. These effects were associated with reduced FPR signalling in the gut as shown by the significant reduction in the levels of p-p38. Collectively, these findings suggest that homeostatic FPR signalling exerts a modulatory effect on anxiety-like behaviours. These findings thus suggest that therapies targeting FPRs may be a novel approach to ameliorate behavioural abnormalities present in neuropsychiatric disorders at the cognitive-emotional interface

Diffractive Higgs Production by AdS Pomeron Fusion

The double diffractive Higgs production at central rapidity is formulated in terms of the fusion of two AdS gravitons/Pomerons first introduced by Brower, Polchinski, Strassler and Tan in elastic scattering. Here we propose a simple self-consistent holographic framework capable of providing phenomenologically compelling estimates of diffractive cross sections at the LHC. As in the traditional weak coupling approach, we anticipate that several phenomenological parameters must be tested and calibrated through factorization for a self-consistent description of other diffractive process such as total cross sections, deep inelastic scattering and heavy quark production in the central region.Comment: 53 pages, 8 figure

Pan-european assessment, monitoring, and mitigation of stressors on the health of bees

Within the PoshBee Project we have tested three bee species – honey bees Apis mellifera, bumble bees Bombus terrestris and solitary bees Osmia bicornis – for their sensitivity to pesticides and analysed the clearance of pesticides from bees. For each species, all castes and sexes were studied. We synthesised the mortality data (LD50 or results of limit tests) with the toxicokinetic patterns and analysed this against the background of inter- and intraspecific variation in life-histories of the tested bees. The clearance of sulfoxaflor is relatively similar across all bee species tested and in females after contact treatment it tends to be retained. The toxicity increases over time independently of the clearance from the body. The clearance of azoxystrobin was rapid in Osmia and bumble bees, as well as in honey bee queens, but in honey bee workers there was very little clearance. Similar to sulfoxaflor the toxicity increased over time, although the residues were detected at very low levels. Glyphosate tended to be retained in bumble bees after contact treatment but cleared rapidly after oral treatment. For Osmia bees only in males after contact treatment was the glyphosate almost lost. The toxicity of a pesticide is dependent on the exact dosage, but also the exposure route and time, as well as the speed of detoxification and clearance from a body. The assessment for the hazard that a less toxic pesticide might pose, can be largely dependent on the exposure route. The effects of pesticide toxicity can increase even after the molecules have been cleared out of the body.Prepared under contract from the European Commission; Grant agreement No. 773921; EU Horizon 2020 Research and Innovation action.Prepared under contract from the European Commission; Grant agreement No. 773921; EU Horizon 2020 Research and Innovation action

Pan-european assessment, monitoring, and mitigation of stressors on the health of bees

Inter-individual differences in pesticide sensitivity may trigger variability in the risk posed by pesticides. Therefore, to better inform pesticide risk assessment for bees, we studied the variability of responses to several pesticides based on endogenous (developmental stage, genetic background, caste) and exogenous factors (pesticide co-exposure). We mainly investigated the toxicity of the insecticide sulfoxaflor, the fungicide azoxystrobin and the herbicide glyphosate. We first used LD50 tests to determine the acute oral and contact toxicity of these pesticides across the different bee species, developmental stages (larva vs adult in honey bees), castes (honey bee and bumble bee workers, queens and drones), and genetic backgrounds (honey bee subspecies). We then considered the risks posed by chronic and sublethal exposures to pesticides by implementing behavioural and reproductive endpoints in the screening of pesticide toxicity. Data showed that azoxystrobin and glyphosate under the test conditions were mildly toxic to bees. However, a large variability in bee sensitivity to sulfoxaflor was found, especially across species and individuals of different castes or sex. This variability is therefore important to consider for increasing the safety margin of the risk posed by insecticides in bees. Several effects induced by sublethal concentrations or doses of pesticides are also described, such as the occurrence of a Non-Monotonic Dose-Response (NMDR) and delayed effects in honey bees, impairment of reproductive performances in bumble bees, and a decreased longevity of Osmia adult females (although no effects were found on larval development). Finally, an interaction between pesticides was found when exposure was by contact, but not under oral exposure. In conclusion, the range of effects described here provides very useful insights for better understanding the toxicity of pesticides and therefore the risks they might pose to bees.Prepared under contract from the European Commission; Grant agreement No. 773921; EU Horizon 2020 Research and Innovation action.Prepared under contract from the European Commission; Grant agreement No. 773921; EU Horizon 2020 Research and Innovation action