Neuropsychological Testing and Machine Learning Distinguish Alzheimer’s Disease from Other Causes for Cognitive Impairment

With promising results in recent treatment trials for Alzheimer’s disease (AD), it becomes increasingly important to distinguish AD at early stages from other causes for cognitive impairment. However, existing diagnostic methods are either invasive (lumbar punctures, PET) or inaccurate Magnetic Resonance Imaging (MRI). This study investigates the potential of neuropsychological testing (NPT) to specifically identify those patients with possible AD among a sample of 158 patients with Mild Cognitive Impairment (MCI) or dementia for various causes. Patients were divided into an early stage and a late stage group according to their Mini Mental State Examination (MMSE) score and labeled as AD or non-AD patients based on a post-mortem validated threshold of the ratio between total tau and beta amyloid in the cerebrospinal fluid (CSF; Total tau/Aβ(1–42) ratio, TB ratio). All patients completed the established Consortium to Establish a Registry for Alzheimer’s Disease—Neuropsychological Assessment Battery (CERAD-NAB) test battery and two additional newly-developed neuropsychological tests (recollection and verbal comprehension) that aimed at carving out specific Alzheimer-typical deficits. Based on these test results, an underlying AD (pathologically increased TB ratio) was predicted with a machine learning algorithm. To this end, the algorithm was trained in each case on all patients except the one to predict (leave-one-out validation). In the total group, 82% of the patients could be correctly identified as AD or non-AD. In the early group with small general cognitive impairment, classification accuracy was increased to 89%. NPT thus seems to be capable of discriminating between AD patients and patients with cognitive impairment due to other neurodegenerative or vascular causes with a high accuracy, and may be used for screening in clinical routine and drug studies, especially in the early course of this disease

A proposed new definition of mental health

The authors propose a new approach to the definition of mental health, different than the definition proposed by the World Health Organization, which is established around issues of person's well-being and productivity. It is supposed to reflect the complexity of human life experience

Endovascular Therapy for Acute Stroke

Stroke is the most common cause of permanent disability, the second most common cause of dementia, and the fourth most common cause of death in the Western world. Recently, based on positive multicenter randomized clinical trials, endovascular therapy for acute stroke has undergone a revolution. Routine mechanical thrombectomy in addition to intravenous thrombolysis has been shown to provide excellent outcomes for patients with proximal anterior circulation occlusions. This procedure reduces disability and benefits are seen across a wide range of age and initial stroke severity. Important features that affect treatment decisions include time of presentation, the patient's clinical status, imaging characteristics, and lab tests. Under optimal conditions, it should be available to patients 24/7, similar to systems offering prompt percutaneous coronary interventions to patients with acute ST-segment elevation myocardial infarctions

Selektion und Evolution: Ein Schülersimulationsexperiment zur selektiven Wirkung der Räuber-Beute-Beziehung

In dieser Unterrichtseinheit wird am Beispiel des Birkenspanners das Phänomen der gerichteten Selektion erarbeitet und mit einem Selektions-Simulations-Experiment veranschaulicht. Dabei erfolgt eine Verknüpfung der genetischen (Vererbbarkeit und Variabilität von Merkmalen), ökologischen (Räuber-Beute-Beziehung und negative Rückkoppelung in Ökosystemen) und evolutiven (Selektion und Anpassung) Aspekte des Phänomens. Auf der methodischen Ebene ermöglicht dieses Simulationsexperiment die Anwendung aller in den vorherigen Experimenten erlernten Kompetenzen

Knowledge acquisition and knowledge structuring for sustainable management in the food trade through concept maps

Die Berufsbildung für eine nachhaltige Entwicklung zielt darauf ab, die Bereitschaft und die Kompetenzen für nachhaltigkeitsorientiertes berufliches Handeln zu fördern. Bedingung dafür ist ein handlungswirksames Wissen. Der Beitrag beleuchtet vor diesem Hintergrund die Potenziale von Concept Maps zum Wissenserwerb und zur -strukturierung und in diesem Zuge Ergebnisse der Zusatzqualifikation für nachhaltiges Wirtschaften im Lebensmittelhandwerk „mach.werk“. (DIPF/Orig.)Vocational education and training for sustainable development aims to promote the readiness and competencies for sustainability-oriented professional action. A prerequisite for this is actionable knowledge. Against this background, the article highlights the potential of concept maps for knowledge acquisition and structuring and, in this context, the results of the additional qualification for sustainable management in the food trade “mach.werk”. (DIPF/Orig.

Symmetry based determination of space-time functions in nonequilibrium growth processes

We study the space-time correlation and response functions in nonequilibrium growth processes described by linear stochastic Langevin equations. Exploiting exclusively the existence of space and time dependent symmetries of the noiseless part of these equations, we derive expressions for the universal scaling functions of two-time quantities which are found to agree with the exact expressions obtained from the stochastic equations of motion. The usefulness of the space-time functions is illustrated through the investigation of two atomistic growth models, the Family model and the restricted Family model, which are shown to belong to a unique universality class in 1+1 and in 2+1 space dimensions. This corrects earlier studies which claimed that in 2+1 dimensions the two models belong to different universality classes.Comment: 18 pages, three figures included, submitted to Phys. Rev.

Retention and Functional Effect of Adipose-Derived Stromal Cells Administered in Alginate Hydrogel in a Rat Model of Acute Myocardial Infarction

Background. Cell therapy for heart disease has been proven safe and efficacious, despite poor cell retention in the injected area. Improving cell retention is hypothesized to increase the treatment effect. In the present study, human adipose-derived stromal cells (ASCs) were delivered in an in situ forming alginate hydrogel following acute myocardial infarction (AMI) in rats. Methods. ASCs were transduced with luciferase and tested for ASC phenotype. AMI was inducted in nude rats, with subsequent injection of saline (controls), 1 × 106 ASCs in saline or 1 × 106 ASCs in 1% (w/v) alginate hydrogel. ASCs were tracked by bioluminescence and functional measurements were assessed by magnetic resonance imaging (MRI) and 82rubidium positron emission tomography (PET). Results. ASCs in both saline and alginate hydrogel significantly increased the ejection fraction (7.2% and 7.8% at 14 days and 7.2% and 8.0% at 28 days, resp.). After 28 days, there was a tendency for decreased infarct area and increased perfusion, compared to controls. No significant differences were observed between ASCs in saline or alginate hydrogel, in terms of retention and functional salvage. Conclusion. ASCs improved the myocardial function after AMI, but administration in the alginate hydrogel did not further improve retention of the cells or myocardial function

Direct intramyocardial plasmid vascular endothelial growth factor-A165gene therapy in patients with stable severe angina pectoris A randomized double-blind placebo-controlled study: The Euroinject One trial

ObjectivesIn the Euroinject One phase II randomized double-blind trial, therapeutic angiogenesis of percutaneous intramyocardial plasmid gene transfer of vascular endothelial growth factor (phVEGF-A165) on myocardial perfusion, left ventricular function, and clinical symptoms was assessed.BackgroundEvidence for safety and treatment efficacy have been presented in phase I therapeutic angiogenesis trials.MethodsEighty “no-option” patients with severe stable ischemic heart disease, Canadian Cardiovascular Society functional class 3 to 4, were assigned randomly to receive, via the NOGA-MyoStar system (Cordis Corp., Miami Lakes, Florida), either 0.5 mg of phVEGF-A165(n = 40) or placebo plasmid (n = 40) in the myocardial region showing stress-induced myocardial perfusion defects on 99mTc sestamibi/tetrofosmin single-photon emission computed tomography.ResultsNo differences among the groups were recorded at baseline with respect to clinical, perfusion, and wall motion characteristics. After three months, myocardial stress perfusion defects did not differ significantly between the VEGF gene transfer and placebo groups (38 ± 3% and 44 ± 2%, respectively). Similarly, semiquantitative analysis of the change in perfusion in the treated region of interest did not differ significantly between the two groups. Compared with placebo, VEGF gene transfer improved the local wall motion disturbances, assessed both by NOGA (p = 0.04) and contrast ventriculography (p = 0.03). Canadian Cardiovascular Society functional class classification of angina pectoris improved significantly in both groups but without difference between the groups. No phVEGF-A165-related adverse events were observed; however, NOGA procedure-related adverse events occurred in five patients.ConclusionsThe VEGF gene transfer did not significantly improve stress-induced myocardial perfusion abnormalities compared with placebo; however, improved regional wall motion, as assessed both by NOGA and by ventriculography, may indicate a favorable anti-ischemic effect. This result should encourage more studies within the field. Transient VEGF overexpression seems to be safe

Angiogenesis PET Tracer Uptake (⁶⁸Ga-NODAGA-E[(cRGDyK)]₂) in Induced Myocardial Infarction and Stromal Cell Treatment in Minipigs

Angiogenesis is considered integral to the reparative process after ischemic injury. The αvβ3 integrin is a critical modulator of angiogenesis and highly expressed in activated endothelial cells. 68Ga-NODAGA-E[(cRGDyK)]2 (RGD) is a positron-emission-tomography (PET) ligand targeted towards αvβ3 integrin. The aim was to present data for the uptake of RGD and correlate it with histology and to further illustrate the differences in angiogenesis due to porcine adipose-derived mesenchymal stromal cell (pASC) or saline treatment in minipigs after induction of myocardial infarction (MI). Three minipigs were treated with direct intra-myocardial injection of pASCs and two minipigs with saline. MI was confirmed by 82Rubidium (82Rb) dipyridamole stress PET. Mean Standardized Uptake Values (SUVmean) of RGD were higher in the infarct compared to non-infarct area one week and one month after MI in both pASC-treated (SUVmean: 1.23 vs. 0.88 and 1.02 vs. 0.86, p < 0.05 for both) and non-pASC-treated minipigs (SUVmean: 1.44 vs. 1.07 and 1.26 vs. 1.04, p < 0.05 for both). However, there was no difference in RGD uptake, ejection fractions, coronary flow reserves or capillary density in histology between the two groups. In summary, indications of angiogenesis were present in the infarcted myocardium. However, no differences between pASC-treated and non-pASC-treated minipigs could be demonstrated