Modular Design Patterns for Hybrid Learning and Reasoning Systems: a taxonomy, patterns and use cases

The unification of statistical (data-driven) and symbolic (knowledge-driven) methods is widely recognised as one of the key challenges of modern AI. Recent years have seen large number of publications on such hybrid neuro-symbolic AI systems. That rapidly growing literature is highly diverse and mostly empirical, and is lacking a unifying view of the large variety of these hybrid systems. In this paper we analyse a large body of recent literature and we propose a set of modular design patterns for such hybrid, neuro-symbolic systems. We are able to describe the architecture of a very large number of hybrid systems by composing only a small set of elementary patterns as building blocks. The main contributions of this paper are: 1) a taxonomically organised vocabulary to describe both processes and data structures used in hybrid systems; 2) a set of 15+ design patterns for hybrid AI systems, organised in a set of elementary patterns and a set of compositional patterns; 3) an application of these design patterns in two realistic use-cases for hybrid AI systems. Our patterns reveal similarities between systems that were not recognised until now. Finally, our design patterns extend and refine Kautz' earlier attempt at categorising neuro-symbolic architectures.Comment: 20 pages, 22 figures, accepted for publication in the International Journal of Applied Intelligenc

Risk of regional recurrence in triple-negative breast cancer patients: a Dutch cohort study

Triple-negative breast cancer is associated with early recurrence and low survival rates. Several trials investigate the safety of a more conservative approach of axillary treatment in clinically T1-2N0 breast cancer. Triple-negative breast cancer comprises only 15 % of newly diagnosed breast cancers, which might result in insufficient power for representative results for this subgroup. We aimed to provide a nationwide overview on the occurrence of (regional) recurrences in triple-negative breast cancer patients with a clinically T1-2N0 status. For this cohort study, 2548 women diagnosed between 2005 and 2008 with clinically T1-2N0 triple-negative breast cancer were selected from the Netherlands Cancer Registry. Follow-up data until 2014 were analyzed using Kaplan–Meier. Sentinel lymph node biopsy was performed in 2486 patients, and (completion) axillary lymph node dissection in 562 patients. Final pathologic nodal status was pN0 in 78.5 %, pN1mi in 4.5 %, pN1 in 12.3 %, pN2–3 in 3.6 %, and pNx in 1.1 %. During a follow-up of 5 years, regional recurrence occurred in 2.9 %, local recurrence in 4.2 % and distant recurrence in 12.2 %. Five-year disease-free survival was 78.7 %, distant disease-free survival 80.5 %, and 5-year overall survival 82.3 %. Triple-negative clinically T1-2N0 breast cancer patients rarely develop a regional recurrence. Their disease-free survival is more threatened by distant recurrence, affecting their overall survival. Consequently, it seems justified to include triple-negative breast cancer patients in randomized controlled trials investigating the safety of minimizing axillary staging and treatment

Mindfulness, Acceptance and Catastrophizing in Chronic Pain

OBJECTIVES: Catastrophizing is often the primary target of the cognitive-behavioral treatment of chronic pain. Recent literature on acceptance and commitment therapy (ACT) suggests an important role in the pain experience for the concepts mindfulness and acceptance. The aim of this study is to examine the influence of mindfulness and general psychological acceptance on pain-related catastrophizing in patients with chronic pain. METHODS: A cross-sectional survey was conducted, including 87 chronic pain patients from an academic outpatient pain center. RESULTS: The results show that general psychological acceptance (measured with the AAQ-II) is a strong predictor of pain-related catastrophizing, independent of gender, age and pain intensity. Mindfulness (measured with the MAAS) did not predict levels of pain-related catastrophizing. DISCUSSION: Acceptance of psychological experiences outside of pain itself is related to catastrophizing. Thus, acceptance seems to play a role in the pain experience and should be part of the treatment of chronic pain. The focus of the ACT treatment of chronic pain does not necessarily have to be on acceptance of pain per se, but may be aimed at acceptance of unwanted experiences in general. Mindfulness in the sense of "acting with awareness" is however not related to catastrophizing. Based on our research findings in comparisons with those of other authors, we recommend a broader conceptualization of mindfulness and the use of a multifaceted questionnaire for mindfulness instead of the unidimensional MAAS

Resistance to diet-induced adiposity in cannabinoid receptor-1 deficient mice is not due to impaired adipocyte function

Background: Overactivity and/or dysregulation of the endocannabinoid system (ECS) contribute to development of obesity. In vitro studies indicate a regulatory role for the cannabinoid receptor 1 (CB1) in adipocyte function and CB1-receptor deficient (CB1-/-) mice are resistant to high fat diet-induced obesity. Whether this phenotype of CB1-/- mice is related to altered fat metabolism in adipose tissue is unknown. Methods: We evaluated adipose tissue differentiation/proliferation markers and quantified lipogenic and lipolytic activities in fat tissues of CB1-/- and CB1+/+ mice fed a high-fat (HF) or a high-fat/fish oil (HF/FO) diet as compared to animals receiving a low-fat chow diet. Comparison between HF diet and HF/FO diet allowed to investigate the influence of dietary fat quality on adipose tissue biology in relation to CB1 functioning. Results: The adiposity-resistant phenotype of the CB1-/- mice was characterized by reduced fat mass and adipocyte size in HF and HF/FO-fed CB1-/- mice in parallel to a significant increase in energy expenditure as compared to CB1+/+ mice. The expression levels of adipocyte differentiation and proliferation markers were however maintained in these animals. Consistent with unaltered lipogenic gene expression, the fatty acid synthesis rates in adipose tissues from CB1-/- and CB1+/+ mice were unchanged. Whole-body and adipose-specific lipoprotein lipase (LPL) activities were also not altered in CB1-/- mice. Conclusions: These findings indicate that protection against diet-induced adiposity in CB1-deficient mice is not related to changes in adipocyte function per se, but rather results from increased energy dissipation by oxidative and non-oxidative pathways.

A retrospective in-depth analysis of continuous glucose monitoring datasets for patients with hepatic glycogen storage disease:Recommended outcome parameters for glucose management

Continuous glucose monitoring (CGM) systems have great potential for real-time assessment of glycemic variation in patients with hepatic glycogen storage disease (GSD). However, detailed descriptions and in-depth analysis of CGM data from hepatic GSD patients during interventions are scarce. This is a retrospective in-depth analysis of CGM parameters, acquired in a continuous, real-time fashion describing glucose management in 15 individual GSD patients. CGM subsets are obtained both in-hospital and at home, upon nocturnal dietary intervention (n = 1), starch loads (n = 11) and treatment of GSD Ib patients with empagliflozin (n = 3). Descriptive CGM parameters, and parameters reflecting glycemic variation and glycemic control are considered useful CGM outcome parameters. Furthermore, the combination of first and second order derivatives, cumulative sum and Fourier analysis identified both subtle and sudden changes in glucose management; hence, aiding assessment of dietary and medical interventions. CGM data interpolation for nocturnal intervals reduced confounding by physical activity and diet. Based on these analyses, we conclude that in-depth CGM analysis can be a powerful tool to assess glucose management and optimize treatment in individual hepatic GSD patients

Long-Term Type 1 Diabetes Enhances In-Stent Restenosis after Aortic Stenting in Diabetes-Prone BB Rats

Type 1 diabetic patients have increased risk of developing in-stent restenosis following endovascular stenting. Underlying pathogenetic mechanisms are not fully understood partly due to the lack of a relevant animal model to study the effect(s) of long-term autoimmune diabetes on development of in-stent restenosis. We here describe the development of in-stent restenosis in long-term (~7 months) spontaneously diabetic and age-matched, thymectomized, nondiabetic Diabetes Prone BioBreeding (BBDP) rats (n = 6-7 in each group). Diabetes was suboptimally treated with insulin and was characterized by significant hyperglycaemia, polyuria, proteinuria, and increased HbA1c levels. Stented abdominal aortas were harvested 28 days after stenting. Computerized morphometric analysis revealed significantly increased neointima formation in long-term diabetic rats compared with nondiabetic controls. In conclusion, long-term autoimmune diabetes in BBDP rats enhances in-stent restenosis. This model can be used to study the underlying pathogenetic mechanisms of diabetes-enhanced in-stent restenosis as well as to test new therapeutic modalities