Recurrent policy gradients

Reinforcement learning for partially observable Markov decision problems (POMDPs) is a challenge as it requires policies with an internal state. Traditional approaches suffer significantly from this shortcoming and usually make strong assumptions on the problem domain such as perfect system models, state-estimators and a Markovian hidden system. Recurrent neural networks (RNNs) offer a natural framework for dealing with policy learning using hidden state and require only few limiting assumptions. As they can be trained well using gradient descent, they are suited for policy gradient approaches. In this paper, we present a policy gradient method, the Recurrent Policy Gradient which constitutes a model-free reinforcement learning method. It is aimed at training limited-memory stochastic policies on problems which require long-term memories of past observations. The approach involves approximating a policy gradient for a recurrent neural network by backpropagating return-weighted characteristic eligibilities through time. Using a ‘‘Long Short-Term Memory'' RNN architecture, we are able to outperform previous RL methods on three important benchmark tasks. Furthermore, we show that using history-dependent baselines helps reducing estimation variance significantly, thus enabling our approach to tackle more challenging, highly stochastic environment

Patient experiences during the COVID-19 pandemic:A qualitative study in Dutch primary care

Background Changes in primary care provision during the COVID-19 pandemic could have affected patient experience of primary care both positively and negatively. Aim To assess the experiences of patients in primary care during the COVID-19 pandemic. Design & setting A qualitative study of patients from regions with high and low COVID-19 prevalence in the Netherlands. Method A qualitative study using a phenomenological framework was performed among purposively sampled patients. Individual semi-structured interviews were performed and transcribed. Data were thematically analysed by means of an inductive approach. Results Twenty-eight patients were interviewed (13 men and 15 women, aged 27–91 years). After thematic analysis, two main themes emerged: accessibility and continuity of primary care. Changes considered positive during the pandemic regarding accessibility and continuity of primary care included having a quieter practice, having more time for consultations, and the use of remote care for problems with low complexity. However, patients also experienced decreases in both care accessibility and continuity, such as feeling unwelcome, the GP postponing chronic care, seeing unfamiliar doctors, and care being segregated. Conclusion Despite bringing several benefits, patients indicated that the changes to primary care provision during the COVID-19 pandemic could have threatened care accessibility and continuity, which are core values of primary care. These insights can guide primary care provision not only in this and future pandemics, but also when implementing permanent changes to care provision in primary care

Deep learning-based breast region segmentation in raw and processed digital mammograms:generalization across views and vendors

Purpose: We developed a segmentation method suited for both raw (for processing) and processed (for presentation) digital mammograms (DMs) that is designed to generalize across images acquired with systems from different vendors and across the two standard screening views. Approach: A U-Net was trained to segment mammograms into background, breast, and pectoral muscle. Eight different datasets, including two previously published public sets and six sets of DMs from as many different vendors, were used, totaling 322 screen film mammograms (SFMs) and 4251 DMs (2821 raw/processed pairs and 1430 only processed) from 1077 different women. Three experiments were done: first training on all SFM and processed images, second also including all raw images in training, and finally testing vendor generalization by leaving one dataset out at a time. Results: The model trained on SFM and processed mammograms achieved a good overall performance regardless of projection and vendor, with a mean (±std. dev.) dice score of 0.96 0.06 for all datasets combined. When raw images were included in training, the mean (±std. dev.) dice score for the raw images was 0.95 0.05 and for the processed images was 0.96 0.04. Testing on a dataset with processed DMs from a vendor that was excluded from training resulted in a difference in mean dice varying between −0.23 to þ0.02 from that of the fully trained model. Conclusions: The proposed segmentation method yields accurate overall segmentation results for both raw and processed mammograms independent of view and vendor. The code and model weights are made available.</p

Science-based GHG emissions targets for agriculture and forestry commodities

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Non-Q wave myocardial infarction: Identification of high and low risk subsets by clinical variables

[This corrects the article DOI: 10.1371/journal.pone.0160243.]

What can we learn from experiences in general practice during the COVID-19 pandemic?:A qualitative study

Background: Experiences with organizational changes in daytime general practices and out-of-hours (OOH) services during the COVID-19 pandemic may help to address the challenges in general practice care that were already a concern before the crisis. This study aimed to describe these experiences and the potential usefulness of the organizational changes for future general practice care and any future pandemics.Methods: Semi-structured interviews were performed among 11 directors of OOH services, and 19 (locum) general practitioners (GPs) or practice managers, who were purposively sampled. Video or telephone interviews were performed in two rounds: between November 2020 and January 2021 and between May 2021 and August 2021. The data were analyzed using thematic analysis methods.Results: Three themes emerged from the data: (1) Changes in the triage procedures; in GP practices and OOH services, stricter triage criteria were implemented, and GPs were more actively involved in the triage process. These measures helped to reduce the number of ‘low urgency’ face-to-face consultations. (2) Changes in GP care; there was a shift towards video and telephone consultations, allowing GPs to spend more time with patients during the remaining face-to-face consultations. For chronic patients, the shift towards telemonitoring appeared to encourage self-care, and postponing face-to-face consultations for regular checkups appeared to be unproblematic for stable patients. (3) Coordination of GP care and information communication flow during the COVID-19 pandemic; OOH directors perceived a lack of consistency in the information from various governmental and non-governmental parties on containment measures and guidelines related to COVID-19, making it difficult to act on them. The COVID-19 pandemic intensified collaboration between GPs, OOH services, and other healthcare professionals.Conclusions: The results of this study indicate that some of the organizational changes, such as stricter triage, remote consultations, and changes in managed care of chronic patients, may help in tackling the pre-existing challenges in GP care from before the COVID-19 pandemic. However, more extensive research and continuous monitoring are necessary to establish the effects on patients and their health outcomes. To navigate future pandemics, the intensified collaboration between health professionals should be maintained, while there is considerable room for improvement in the provision of unambiguous information.</p

Imidazo[2,1-b] [1,3,4]thiadiazoles with antiproliferative activity against primary and gemcitabine-resistant pancreatic cancer cells

A new series of eighteen imidazo [2,1-b] [1,3,4]thiadiazole derivatives was efficiently synthesized and screened for antiproliferative activity against the National Cancer Institute (NCI-60) cell lines panel. Two out of eighteen derivatives, compounds 12a and 12h, showed remarkably cytotoxic activity with the half maximal inhibitory concentration values (IC50) ranging from 0.23 to 11.4 mM, and 0.29e12.2 mM, respectively. However, two additional compounds, 12b and 13g, displayed remarkable in vitro antiproliferative activity against pancreatic ductal adenocarcinoma (PDAC) cell lines, including immortalized (SUIT-2, Capan-1, Panc-1), primary (PDAC-3) and gemcitabine-resistant (Panc-1R), eliciting IC50 values ranging from micromolar to sub-micromolar level, associated with significant reduction of cell-migration and spheroid shrinkage. These remarkable results might be explained by modulation of key regulators of epithelial-to-mesenchymal transition (EMT), including E-cadherin and vimentin, and inhibition of metalloproteinase-2/-9. High-throughput arrays revealed a significant inhibition of the phosphorylation of 45 tyrosine kinases substrates, whose visualization on Cytoscape highlighted PTK2/FAK as an important hub. Inhibition of phosphorylation of PTK2/FAK was validated as one of the possible mechanisms of action, using a specific ELISA. In conclusion, novel imidazothiadiazoles show potent antiproliferative activity, mediated by modulation of EMT and PTK2/FAK

The clinical and prognostic value of late Gadolinium enhancement imaging in heart failure with mid-range and preserved ejection fraction

Heart failure (HF) with mid-range or preserved ejection fraction (HFmrEF; HFpEF) is a heterogeneous disorder that could benefit from strategies to identify subpopulations at increased risk. We tested the hypothesis that HFmrEF and HFpEF patients with myocardial scars detected with late gadolinium enhancement (LGE) are at increased risk for all-cause mortality. Symptomatic HF patients with left ventricular ejection fraction (LVEF) > 40%, who underwent cardiac magnetic resonance (CMR) imaging were included. The presence of myocardial LGE lesions was visually assessed. T1 mapping was performed to calculate extracellular volume (ECV). Multivariable logistic regression analyses were used to determine associations between clinical characteristics and LGE. Cox regression analyses were used to assess the association between LGE and all-cause mortality. A total of 110 consecutive patients were included (mean age 71 +/- 10 years, 49% women, median N-terminal brain natriuretic peptide (NT-proBNP) 1259 pg/ml). LGE lesions were detected in 37 (34%) patients. Previous myocardial infarction and increased LV mass index were strong and independent predictors for the presence of LGE (odds ratio 6.32, 95% confidence interval (CI) 2.07-19.31, p = 0.001 and 1.68 (1.03-2.73), p = 0.04, respectively). ECV was increased in patients with LGE lesions compared to those without (28.6 vs. 26.6%, p = 0.04). The presence of LGE lesions was associated with a fivefold increase in the incidence of all-cause mortality (hazards ratio 5.3, CI 1.5-18.1, p = 0.009), independent of age, sex, New York Heart Association (NYHA) functional class, NT-proBNP, LGE mass and LVEF. Myocardial scarring on CMR is associated with increased mortality in HF patients with LVEF > 40% and may aid in selecting a subpopulation at increased risk

Altered Gut Microbial Fermentation and Colonization with Methanobrevibacter smithii in Renal Transplant Recipients

Renal transplant recipients (RTRs) often suffer from posttransplant diarrhea. The observed dysbiosis in RTR may influence the fermentation processes in the gut. In this study, we aimed to investigate whether fermentation differs between RTRs and healthy controls (HCs), by measuring breath H2 and CH4 concentrations. Additionally, we determined the fecal presence of the methanogen Methanobrevibacter smithii (M. smithii), which plays a main role in the process of methanogenesis. Data from the TransplantLines Biobank and Cohort Study (NCT03272841) was used. A total of 142 RTRs and 77 HCs were included. Breath H2 concentrations in RTRs were not significantly different from HCs. Breath CH4 concentrations in RTRs were significantly lower compared with HCs (median [interquartile range (IQR)] 7.5 [3.9–10.6] ppm vs. 16.0 [8.0–45.5] ppm, p < 0.001). M. smithii was less frequently present in the feces of RTRs compared to HCs (28.6% vs. 86.4% resp., p < 0.001). Our findings regarding the altered methanogenesis in the gut of RTRs show similarities with previous results in inflammatory bowel disease patients. These findings provide novel insight into the alterations of fermentation after renal transplantation, which may contribute to understanding the occurrence of posttransplant diarrhea. View Full-Tex

Validation of separate multi-atlases for auto segmentation of cardiac substructures in CT-scans acquired in deep inspiration breath hold and free breathing

Background and purpose: Developing NTCP-models for cardiac complications after breast cancer (BC) radiotherapy requires cardiac dose-volume parameters for many patients. These can be obtained by using multi-atlas based automatic segmentation (MABAS) of cardiac structures in planning CT scans. We investigated the relevance of separate multi-atlases for deep inspiration breath hold (DIBH) and free breathing (FB) CT scans. Materials and methods: BC patients scanned in DIBH (n = 10) and in FB (n = 20) were selected to create separate multi-atlases consisting of expert panel delineations of the whole heart, atria and ventricles. The accuracy of atlas-generated contours was validated with expert delineations in independent datasets (n = 10 for DIBH and FB) and reported as Dice coefficients, contour distances and dose-volume differences in relation to interobserver variability of manual contours. Dependency of MABAS contouring accuracy on breathing technique was assessed by validation of a FB atlas in DIBH patients and vice versa (cross validation). Results: For all structures the FB and DIBH atlases resulted in Dice coefficients with their respective reference contours > 0.8 and average contour distances < 2 mm smaller than slice thickness of (CTs). No significant differences were found for dose-volume parameters in volumes receiving relevant dose levels (WH, LV and RV). Accuracy of the DIBH atlas was at least similar to, and for the ventricles better than, the interobserver variation in manual delineation. Cross-validation between breathing techniques showed a reduced MABAS performance. Conclusion: Multi-atlas accuracy was at least similar to interobserver delineation variation. Separate atlases for scans made in DIBH and FB could benefit atlas performance because accuracy depends on breathing technique