Geometrie virtuell fassbar gemacht : mehr Freude am Mathematik-Unterricht durch interaktive Computerprogramme

Computer haben im Mathematik-Unterricht bisher vor allem die Funktion, Abstraktes bildlich zu veranschaulichen. Neu sind interaktive Programme, mit denen Schüler experimentieren und spielerisch ein Gefühl für Zusammenhänge entwickeln können. Erste Versuche zeigen, dass dieses Angebot, »Mathematik erfahrbar zu machen«, die Schüler stark motiviert. Computer sind wichtige Mittler zwischen der realen Welt und den Abstraktionen ihrer mathematischen Beschreibung. Denn: Mathematik wohnt den Dingen nicht inne, man sieht sie mit dem »mathematischen Blick« in die Dinge hinein. Erst dadurch gliedert sich der Raum um uns in Punkte, Strecken, Ebenen und all die anderen geometrischen Objekte. Diese Objekte selbst sind nicht real, und materielle Modelle, die wir zu ihrer Veranschaulichung heranziehen, unterliegen Einschränkungen, von denen man abstrahieren muss. Wir zeigen anhand zweier aktueller Entwicklungs- und Forschungsprojekte, wie Computer helfen können, diese Kluft zu überbrücken. ..

The impact of heterogeneity and geometry on the proof complexity of random satisfiability

Satisfiability is considered the canonical NP-complete problem and is used as a starting point for hardness reductions in theory, while in practice heuristic SAT solving algorithms can solve large-scale industrial SAT instances very efficiently. This disparity between theory and practice is believed to be a result of inherent properties of industrial SAT instances that make them tractable. Two characteristic properties seem to be prevalent in the majority of real-world SAT instances, heterogeneous degree distribution and locality. To understand the impact of these two properties on SAT, we study the proof complexity of random -SAT models that allow to control heterogeneity and locality. Our findings show that heterogeneity alone does not make SAT easy as heterogeneous random -SAT instances have superpolynomial resolution size. This implies intractability of these instances for modern SAT-solvers. In contrast, modeling locality with underlying geometry leads to small unsatisfiable subformulas, which can be found within polynomial time

Complex regional pain syndrome in adults

Abstract Complex regional pain syndrome (CRPS) is a highly painful, limb-confined condition, which arises usually after trauma. It is associated with a particularly poor quality of life, and large health-care and societal costs. The causes of CRPS remain unknown. The condition's distinct combination of abnormalities includes limb-confined inflammation and tissue hypoxia, sympathetic dysregulation, small fibre damage, serum autoantibodies, central sensitization and cortical reorganization. These features place CRPS at a crossroads of interests of several disciplines including rheumatology, pain medicine and neurology. Significant scientific and clinical advances over the past 10 years hold promise both for an improved understanding of the causes of CRPS, and for more effective treatments. This review summarizes current concepts of our understanding of CRPS in adults. Based on the results from systematic reviews, treatment approaches are discussed within the context of these concepts. The treatment of CRPS is multidisciplinary and aims to educate about the condition, sustain or restore limb function, reduce pain and provide psychological intervention. Results from recent randomized controlled trials suggest that it is possible that some patients whose condition was considered refractory in the past can now be effectively treated, but confirmatory trials are required. The review concludes with a discussion of the need for additional research

Explainable Artificial Intelligence: Concepts, Applications, Research Challenges and Visions

The development of theory, frameworks and tools for Explainable AI (XAI) is a very active area of research these days, and articulating any kind of coherence on a vision and challenges is itself a challenge. At least two sometimes complementary and colliding threads have emerged. The first focuses on the development of pragmatic tools for increasing the transparency of automatically learned prediction models, as for instance by deep or reinforcement learning. The second is aimed at anticipating the negative impact of opaque models with the desire to regulate or control impactful consequences of incorrect predictions, especially in sensitive areas like medicine and law. The formulation of methods to augment the construction of predictive models with domain knowledge can provide support for producing human understandable explanations for predictions. This runs in parallel with AI regulatory concerns, like the European Union General Data Protection Regulation, which sets standards for the production of explanations from automated or semi-automated decision making. Despite the fact that all this research activity is the growing acknowledgement that the topic of explainability is essential, it is important to recall that it is also among the oldest fields of computer science. In fact, early AI was re-traceable, interpretable, thus understandable by and explainable to humans. The goal of this research is to articulate the big picture ideas and their role in advancing the development of XAI systems, to acknowledge their historical roots, and to emphasise the biggest challenges to moving forward

Sham controls in device trials for chronic pain – tricky in practice-a review article

BACKGROUND: Chronic pain affects one in four people and this figure is likely to increase further in line with an ageing population. Efforts to evaluate nonpharmacological interventions to support this patient population have become a priority for pain research. For device trials, the use of a sham control can add to the scientific validity and quality of a study. However, only a small proportion of pain trials include a sham control, and many are of poor quality. To facilitate the conduct of high-quality trials there is a need for a comprehensive overview to guide researchers within this area. The objective of this review was to synthesise the published data to address this need. METHODS: We identified studies that considered the evaluation, design, and conduct of sham-controlled trials in chronic pain by searching MEDLINE, CINAHL and Science Direct to November 2022. Studies that included sufficient content to inform the conduct/design of future research were included. An inductive thematic analysis approach was used to identify themes that require consideration when conducting sham-controlled trials. These are presented as a narrative review. RESULTS: 37 articles were included. Identified themes related to the type of sham device, sham design, bias, study population and ethics. CONCLUSIONS: To conduct good quality research the challenges surrounding the use of sham interventions need to be better considered. We highlight salient issues and provide recommendations for the conduct and reporting of sham-controlled device trials in chronic pain

Dermal nerve fibre and mast cell density, and proximity of mast cells to nerve fibres in the skin of patients with complex regional pain syndrome

An interaction between cutaneous nerves and mast cells may contribute to pain in complex regional pain syndrome (CRPS). To explore this, we investigated the density of dermal nerve fibres, and the density and proximity of mast cells to nerve fibres, in skin biopsies obtained from the affected and unaffected limbs of 57 patients with CRPS and 28 site-matched healthy controls. The percentage of the dermis stained by the pan-neuronal marker protein gene-product 9.5 was lower in the affected limb of patients than in controls (0.12 ± 0.01% versus 0.22 ± 0.04%, P \u3c 0.05), indicating a reduction in dermal nerve fibre density. This parameter did not correlate with CRPS duration. However, it was lower in the affected than unaffected limb of patients with warm CRPS. Dermal mast cell numbers were similar in patients and controls, but the percentage of mast cells less than 5 μm from nerve fibres was significantly lower in the affected and unaffected limbs of patients than in controls (16.8 ±1.7%, 16.5 ± 1.7% and 31.4 ± 2.3% respectively, P \u3c 0.05). We confirm previous findings of a mild neuropathy in CRPS. Our findings suggest that this either develops very early after injury or precedes CRPS onset. Loss of dermal nerve fibres in CRPS might result in loss of chemotactic signals, thus halting mast cell migration towards surviving nerve fibres. Failure of normal nerve fibre-mast cell interactions could contribute to the pathophysiology of CRPS

A randomised, patient-assessor blinded, sham-controlled trial of external noninvasive peripheral nerve stimulation for chronic neuropathic pain following peripheral nerve injury (EN-PENS trial):study protocol for a randomised controlled trial

BACKGROUND: Eight percent of people in the UK are estimated to have persistent (chronic) neuropathic pain, and for many there is no effective treatment. Medications are the most common first-line treatment but often have limited benefit or adverse events. Surgical treatments, such as spinal cord stimulation, are then often considered. External non-invasive peripheral nerve stimulation (EN-PENS) is a form of electrical stimulation that involves placing a pen-shaped electrode onto the skin, which can be easily self-administered by patients. Observational studies suggest that EN-PENS may relieve pain for people with localised neuropathic pain; however, there is currently no evidence from controlled trials to confirm the efficacy and confidently determine the effect size for patients with longstanding neuropathic pain. METHODS: EN-PENS is a single-site, blinded, randomised controlled parallel-group superiority add-on trial with a 1:1 allocation ratio, designed to evaluate the efficacy of treatment versus control treatment in 76 patients with longstanding neuropathic pain following peripheral nerve injury. Patients with moderate to -severe neuropathic pain following peripheral nerve injury will be randomised to receive either the active or control treatment, followed by an optional treatment extension or treatment switch to the alternative treatment arm. The primary outcome is average 24-h pain intensity recorded on an 11-point (0–10) numerical rating scale, averaged over the last 7 days of treatment. DISCUSSION: Study results will be used to inform potential treatment efficacy and cost-effectiveness of EN-PENS for this population group. TRIAL REGISTRATION: ISRCTN53432663. Registered on 7 July 2016

Proteomic Profiling Unravels a Key Role of Specific Macrophage Subtypes in Sporadic Inclusion Body Myositis

Unbiased proteomic profiling was performed toward the identification of biological parameters relevant in sIBM, thus giving hints about the pathophysiological processes and the existence of new reliable markers. For that purpose, skeletal muscle biopsies from 13 sIBM and 7 non-diseased control patients were analyzed with various methods, including liquid chromatography coupled to tandem mass spectrometry (four patients). Subsequent data analysis identified key molecules further studied in a larger cohort by qPCR, immunostaining, and immunofluorescence in situ. Proteomic signature of muscle biopsies derived from sIBM patients revealed the chaperone and cell surface marker CD74, the macrophage scavenger molecule CD163 and the transcription activator STAT1 to be among the highly and relevantly expressed proteins suggesting a significant contribution of immune cells among the myofibers expressing these markers. Moreover, in silico studies showed that 39% of upregulated proteins were involved in type I or mixed type I and type II interferon immunity. Indeed, further studies via immunohistochemistry clearly confirmed the prominent involvement of the key type I interferon signature-related molecules, ISG15 as well as IRF8 with MHC class II+ myofibers. Siglec1 colocalized with CD163+ macrophages and MHC class II molecules also co-localized with CD74 on macrophages. STAT1 co-localized with Siglec1+ macrophages in activemyofibremyophagocytosis while STAT6 colocalized with endomysial macrophages. These combined results show involvement of CD74, CD163, and STAT1 as key molecules of macrophage activation being crucially involved in mixed and specific type I interferon, and interferon gamma associated-pathways in sIBM. On a more general note, these results also highlight the type of immune-interaction between macrophages and myofibers in the etiopathology of sIBM