Delicate Debates on Islam. Policymakers and Academics Speaking with Each Other: an Introduction

Rule of Law and Development: Formation, Implementation and Improvement of Law and Governance in Developing Countrie

Short-, medium-, and long-term follow-up after percutaneous transluminal coronary angioplasty for stable and unstable angina pectoris

The first 840 consecutive patients who underwent percutaneous transluminal coronary angioplasty (PTCA) performed in the same institution were retrospectively assessed at an average follow-up period of 25 months after the initial procedure. The study population consisted of 506 patients with stable angina pectoris (group 1) and 334 patients with unstable angina pectoris (group 2). Clinical end points were death, nonfatal myocardial infarction, recurrent angina pectoris necessitating bypass surgery or repeat PTCA, and event-free survival. The two groups were comparable with respect to age, sex, previous myocardial infarction, ejection fraction, and number of diseased vessels. PTCA was successful in 83.0% of group 1 and 87.1% of group 2. Follow-up rates were expressed as events per attempted PTCA in a patient group. No difference in survival was observed between the two groups, the mortality rate being approximately 2.8% at 25 months. In the group with stable angina pectoris there was a lower incidence of nonfatal myocardial infarction within the first 24 hours after angioplasty; 4.3% vs 9.0% (p less than 0.01). During long-term follow-up the increase in the incidence of nonfatal myocardial infarction was similar, resulting in an overall long-term follow-up infarction rate of 8.3% and 14.2%, respectively (p less than 0.01). A higher event-free survival was observed in group 1 within 24 hours after PTCA: 93.7% vs 84.2% (p less than 0.01). During subsequent follow-up the difference in event-free survival between the two groups was no longer significant: 68.5% vs 61.2%.(ABSTRACT TRUNCATED AT 250 WORDS

Machine learning-based analysis of [¹⁸F]DCFPyL PET radiomics for risk stratification in primary prostate cancer

PURPOSE: Quantitative prostate-specific membrane antigen (PSMA) PET analysis may provide for non-invasive and objective risk stratification of primary prostate cancer (PCa) patients. We determined the ability of machine learning-based analysis of quantitative [18F]DCFPyL PET metrics to predict metastatic disease or high-risk pathological tumor features. METHODS: In a prospective cohort study, 76 patients with intermediate- to high-risk PCa scheduled for robot-assisted radical prostatectomy with extended pelvic lymph node dissection underwent pre-operative [18F]DCFPyL PET-CT. Primary tumors were delineated using 50-70% peak isocontour thresholds on images with and without partial-volume correction (PVC). Four hundred and eighty standardized radiomic features were extracted per tumor. Random forest models were trained to predict lymph node involvement (LNI), presence of any metastasis, Gleason score ≥ 8, and presence of extracapsular extension (ECE). For comparison, models were also trained using standard PET features (SUVs, volume, total PSMA uptake). Model performance was validated using 50 times repeated 5-fold cross-validation yielding the mean receiver-operator characteristic curve AUC. RESULTS: The radiomics-based machine learning models predicted LNI (AUC 0.86 ± 0.15, p < 0.01), nodal or distant metastasis (AUC 0.86 ± 0.14, p < 0.01), Gleason score (0.81 ± 0.16, p < 0.01), and ECE (0.76 ± 0.12, p < 0.01). The highest AUCs reached using standard PET metrics were lower than those of radiomics-based models. For LNI and metastasis prediction, PVC and a higher delineation threshold improved model stability. Machine learning pre-processing methods had a minor impact on model performance. CONCLUSION: Machine learning-based analysis of quantitative [18F]DCFPyL PET metrics can predict LNI and high-risk pathological tumor features in primary PCa patients. These findings indicate that PSMA expression detected on PET is related to both primary tumor histopathology and metastatic tendency. Multicenter external validation is needed to determine the benefits of using radiomics versus standard PET metrics in clinical practice

Increasing incidence of cancer and stage migration towards advanced disease in children and young adolescents in the Netherlands, 1990–2017

Background: This is the first national study on trends in cancer incidence for children and young adolescents in the Netherlands,

Myeloid ATP citrate lyase regulates macrophage inflammatory responses in vitro without altering inflammatory disease outcomes

Macrophages are highly plastic, key regulators of inflammation. Deregulation of macrophage activation can lead to excessive inflammation as seen in inflammatory disorders like atherosclerosis, obesity, multiple sclerosis and sepsis. Targeting intracellular metabolism is considered as an approach to reshape deranged macrophage activation and to dampen the progression of inflammatory disorders. ATP citrate lyase (Acly) is a key metabolic enzyme and an important regulator of macrophage activation. Using a macrophage-specific Acly-deficient mouse model, we investigated the role of Acly in macrophages during acute and chronic inflammatory disorders. First, we performed RNA sequencing to demonstrate that Acly-deficient macrophages showed hyperinflammatory gene signatures in response to acute LPS stimulation in vitro. Next, we assessed endotoxin-induced peritonitis in myeloid-specific Acly-deficient mice and show that, apart from increased splenic Il6 expression, systemic and local inflammation were not affected by Acly deficiency. Also during obesity, both chronic low-grade inflammation and whole-body metabolic homeostasis remained largely unaltered in mice with Acly-deficient myeloid cells. Lastly, we show that macrophage-specific Acly deletion did not affect the severity of experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis. These results indicate that, despite increasing inflammatory responses in vitro, macrophage Acly deficiency does not worsen acute and chronic inflammatory responses in vivo. Collectively, our results indicate that caution is warranted in prospective long-term treatments of inflammatory disorders with macrophage-specific Acly inhibitors. Together with our earlier observation that myeloid Acly deletion stabilizes atherosclerotic lesions, our findings highlight that therapeutic targeting of macrophage Acly can be beneficial in some, but not all, inflammatory disorders.Host-parasite interactio

The Earth: Plasma Sources, Losses, and Transport Processes

This paper reviews the state of knowledge concerning the source of magnetospheric plasma at Earth. Source of plasma, its acceleration and transport throughout the system, its consequences on system dynamics, and its loss are all discussed. Both observational and modeling advances since the last time this subject was covered in detail (Hultqvist et al., Magnetospheric Plasma Sources and Losses, 1999) are addressed