Landmark Tracking in Liver US images Using Cascade Convolutional Neural Networks with Long Short-Term Memory

This study proposed a deep learning-based tracking method for ultrasound (US) image-guided radiation therapy. The proposed cascade deep learning model is composed of an attention network, a mask region-based convolutional neural network (mask R-CNN), and a long short-term memory (LSTM) network. The attention network learns a mapping from a US image to a suspected area of landmark motion in order to reduce the search region. The mask R-CNN then produces multiple region-of-interest (ROI) proposals in the reduced region and identifies the proposed landmark via three network heads: bounding box regression, proposal classification, and landmark segmentation. The LSTM network models the temporal relationship among the successive image frames for bounding box regression and proposal classification. To consolidate the final proposal, a selection method is designed according to the similarities between sequential frames. The proposed method was tested on the liver US tracking datasets used in the Medical Image Computing and Computer Assisted Interventions (MICCAI) 2015 challenges, where the landmarks were annotated by three experienced observers to obtain their mean positions. Five-fold cross-validation on the 24 given US sequences with ground truths shows that the mean tracking error for all landmarks is 0.65+/-0.56 mm, and the errors of all landmarks are within 2 mm. We further tested the proposed model on 69 landmarks from the testing dataset that has a similar image pattern to the training pattern, resulting in a mean tracking error of 0.94+/-0.83 mm. Our experimental results have demonstrated the feasibility and accuracy of our proposed method in tracking liver anatomic landmarks using US images, providing a potential solution for real-time liver tracking for active motion management during radiation therapy

Full-dose PET Synthesis from Low-dose PET Using High-efficiency Diffusion Denoising Probabilistic Model

To reduce the risks associated with ionizing radiation, a reduction of radiation exposure in PET imaging is needed. However, this leads to a detrimental effect on image contrast and quantification. High-quality PET images synthesized from low-dose data offer a solution to reduce radiation exposure. We introduce a diffusion-model-based approach for estimating full-dose PET images from low-dose ones: the PET Consistency Model (PET-CM) yielding synthetic quality comparable to state-of-the-art diffusion-based synthesis models, but with greater efficiency. There are two steps: a forward process that adds Gaussian noise to a full dose PET image at multiple timesteps, and a reverse diffusion process that employs a PET Shifted-window Vision Transformer (PET-VIT) network to learn the denoising procedure conditioned on the corresponding low-dose PETs. In PET-CM, the reverse process learns a consistency function for direct denoising of Gaussian noise to a clean full-dose PET. We evaluated the PET-CM in generating full-dose images using only 1/8 and 1/4 of the standard PET dose. Comparing 1/8 dose to full-dose images, PET-CM demonstrated impressive performance with normalized mean absolute error (NMAE) of 1.233+/-0.131%, peak signal-to-noise ratio (PSNR) of 33.915+/-0.933dB, structural similarity index (SSIM) of 0.964+/-0.009, and normalized cross-correlation (NCC) of 0.968+/-0.011, with an average generation time of 62 seconds per patient. This is a significant improvement compared to the state-of-the-art diffusion-based model with PET-CM reaching this result 12x faster. In the 1/4 dose to full-dose image experiments, PET-CM is also competitive, achieving an NMAE 1.058+/-0.092%, PSNR of 35.548+/-0.805dB, SSIM of 0.978+/-0.005, and NCC 0.981+/-0.007 The results indicate promising low-dose PET image quality improvements for clinical applications

Radiation, Immune Checkpoint Blockade and the Abscopal Effect: A Critical Review on Timing, Dose and Fractionation

The combination of radiation and immunotherapy is currently an exciting avenue of pre-clinical and clinical investigation. The synergy between these two treatment modalities has the potential to expand the role of radiation from a purely local therapy, to a role in advanced and metastatic disease. Tumor regression outside of the irradiated field, known as the abscopal effect, is a recognized phenomenon mediated by lymphocytes and enhanced by checkpoint blockade. In this review, we summarize the known mechanistic data behind the immunostimulatory effects of radiation and how this is enhanced by immunotherapy. We also provide pre-clinical data supporting specific radiation timing and optimal dose/fractionation for induction of a robust anti-tumor immune response with or without checkpoint blockade. Importantly, these data are placed in a larger context of understanding T-cell exhaustion and the impact of immunotherapy on this phenotype. We also include relevant pre-clinical studies done in non-tumor systems. We discuss the published clinical trials and briefly summarize salient case reports evaluating the abscopal effect. Much of the data discussed here remains at the preliminary stage, and a number of interesting avenues of research remain under investigation

Measurements of ψ(2S) and X(3872) → J/ψπ+π− production in pp collisions at √s=8 TeV with the ATLAS detector

Differential cross sections are presented for the prompt and non-prompt production of the hidden-charm states X(3872) and ψ(2S), in the decay mode J/ψπ+π−, measured using 11.4 fb−1 of pp collisions at √s=8 TeV by the ATLAS detector at the LHC. The ratio of cross-sections X(3872)/ψ(2S) is also given, separately for prompt and non-prompt components, as well as the non-prompt fractions of X(3872) and ψ(2S). Assuming independent single effective lifetimes for non-prompt X(3872) and ψ(2S) production gives RB=B(B→X(3872)+any)B(X(3872)→J/ψπ+π−)B(B→ψ(2S)+any)B(ψ(2S)→J/ψπ+π−)=(3.95±0.32(stat)±0.08(sys))×10−2RB=B(B→X(3872)+any)B(X(3872)→J/ψπ+π−)B(B→ψ(2S)+any)B(ψ(2S)→J/ψπ+π−)=(3.95±0.32(stat)±0.08(sys))×10−2 separating short- and long-lived contributions, assuming that the short-lived component is due to Bc decays, gives RB = (3.57 ± 0.33(stat) ± 0.11(sys)) × 10−2, with the fraction of non-prompt X(3872) produced via Bc decays for pT(X(3872)) > 10 GeV being (25 ± 13(stat) ± 2(sys) ± 5(spin))%. The distributions of the dipion invariant mass in the X(3872) and ψ(2S) decays are also measured and compared to theoretical predictions

Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial

Background: Semaglutide, a GLP-1 receptor agonist, reduces the risk of major adverse cardiovascular events (MACE) in people with overweight or obesity, but the effects of this drug on outcomes in patients with atherosclerotic cardiovascular disease and heart failure are unknown. We report a prespecified analysis of the effect of once-weekly subcutaneous semaglutide 2·4 mg on ischaemic and heart failure cardiovascular outcomes. We aimed to investigate if semaglutide was beneficial in patients with atherosclerotic cardiovascular disease with a history of heart failure compared with placebo; if there was a difference in outcome in patients designated as having heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction; and if the efficacy and safety of semaglutide in patients with heart failure was related to baseline characteristics or subtype of heart failure. Methods: The SELECT trial was a randomised, double-blind, multicentre, placebo-controlled, event-driven phase 3 trial in 41 countries. Adults aged 45 years and older, with a BMI of 27 kg/m2 or greater and established cardiovascular disease were eligible for the study. Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo. In a prespecified analysis, we examined the effect of semaglutide compared with placebo in patients with and without a history of heart failure at enrolment, subclassified as heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, or unclassified heart failure. Endpoints comprised MACE (a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death); a composite heart failure outcome (cardiovascular death or hospitalisation or urgent hospital visit for heart failure); cardiovascular death; and all-cause death. The study is registered with ClinicalTrials.gov, NCT03574597. Findings: Between Oct 31, 2018, and March 31, 2021, 17 604 patients with a mean age of 61·6 years (SD 8·9) and a mean BMI of 33·4 kg/m2 (5·0) were randomly assigned to receive semaglutide (8803 [50·0%] patients) or placebo (8801 [50·0%] patients). 4286 (24·3%) of 17 604 patients had a history of investigator-defined heart failure at enrolment: 2273 (53·0%) of 4286 patients had heart failure with preserved ejection fraction, 1347 (31·4%) had heart failure with reduced ejection fraction, and 666 (15·5%) had unclassified heart failure. Baseline characteristics were similar between patients with and without heart failure. Patients with heart failure had a higher incidence of clinical events. Semaglutide improved all outcome measures in patients with heart failure at random assignment compared with those without heart failure (hazard ratio [HR] 0·72, 95% CI 0·60-0·87 for MACE; 0·79, 0·64-0·98 for the heart failure composite endpoint; 0·76, 0·59-0·97 for cardiovascular death; and 0·81, 0·66-1·00 for all-cause death; all pinteraction>0·19). Treatment with semaglutide resulted in improved outcomes in both the heart failure with reduced ejection fraction (HR 0·65, 95% CI 0·49-0·87 for MACE; 0·79, 0·58-1·08 for the composite heart failure endpoint) and heart failure with preserved ejection fraction groups (0·69, 0·51-0·91 for MACE; 0·75, 0·52-1·07 for the composite heart failure endpoint), although patients with heart failure with reduced ejection fraction had higher absolute event rates than those with heart failure with preserved ejection fraction. For MACE and the heart failure composite, there were no significant differences in benefits across baseline age, sex, BMI, New York Heart Association status, and diuretic use. Serious adverse events were less frequent with semaglutide versus placebo, regardless of heart failure subtype. Interpretation: In patients with atherosclerotic cardiovascular diease and overweight or obesity, treatment with semaglutide 2·4 mg reduced MACE and composite heart failure endpoints compared with placebo in those with and without clinical heart failure, regardless of heart failure subtype. Our findings could facilitate prescribing and result in improved clinical outcomes for this patient group. Funding: Novo Nordisk

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema