Coronabonds are a pragmatic response to a crisis – and are not about cross-EU transfers or solidarity

Common debt instruments created by the European Union, of which coronabonds are currently the most urgent and salient example, evoke in some countries the fear that the Eurozone may be heading towards a ‘transfer union’. Some advocates also misleadingly justify these innovations by an appeal to European ‘solidarity’. Yet, in practice, Michael Paetz and Patrick Kaczmarczyk argue that such instruments require only a dose of pragmatism. We need to fundamentally reframe the debate around ‘debt mutualisation’ in Europe on more evidence-based and realistic lines if the Eurozone is to survive

Modelling and simulation of a stationary high-rise elevator system to predict the dynamic interactions between its components

In a high-rise elevator system lateral vibrations of the suspension and compensating ropes, coupled with vertical motions of the car and counterweight are induced by the building structure motions. When the frequency of the building coincides with the fundamental natural frequency of the ropes, large resonance whirling motions of the ropes result. This phenomenon leads to impacts of the ropes on the elevator walls, large displacements of the car and counterweight making the building and elevator system unsafe. This paper presents a comprehensive mathematical model of a high-rise elevator system taking into account the combined lateral stiffness of the roller guides and guide rails. The results and analysis presented in the paper demonstrate frequency curve veering phenomena and a wide range of resonances that occur in the system. A case study is presented when the car is parked at a landing level where the fundamental natural frequencies of the car, suspension and compensating rope system coincide with one of the natural frequencies of the high-rise building. The results show a range of nonlinear dynamic interactions between the components of the elevator system that play a significant role in the operation of the entire installation

Knowledge and attitudes of men to prostate cancer

Objective: To ascertain the current level of understanding about prostate cancer (PCa), including treatment options and potential side effects of treatment, among older men. Design and Setting: Questionnaires administered by general practitioners (GPs) in 5 general practices in the Perth metropolitan and regional areas of Western Australia. Participants: Convenience sample of men aged 40-80 years (n=503) with or without prostate cancer presenting for routine consultations. Main outcome measures: Knowledge and attitudes of men to prostate cancer Results: Eighty percent of men did not know the function of the prostate and 48% failed to identify PCa as the most common internal cancer in men. Thirty-five percent had no knowledge of the treatments for PCa and 53% had no knowledge of the side effects of treatments. Asked how they would arrive at a decision about treatment, 70% stated they would ask the GP/specialist for all their options and then decide themselves. Conclusion: This study confirms a deficit in knowledge of the disease among men in the at risk age group. Lack of knowledge encompassed areas which could delay diagnosis and hence treatment. Overall the population preferred some GP/specialist involvement in treatment decision making

No association between major depression with and without childhood adversity and the stress hormone copeptin

Background: Adverse childhood experiences (ACE) are associated with an increased risk of major depressive disorder (MDD) and hypothalamic-pituitary-adrenal (HPA) axis dysregulation. Within the HPA axis, corticotropin-releasing hormone and vasopressin (AVP) synergistically stimulate the release of adrenocorticotropic hormone, which promotes cortisol release. The cleavage product copeptin is produced during AVP synthesis and is a surrogate marker of AVP release. Children with ACE and young adults with depressive symptoms have higher levels of copeptin than healthy controls. Objective: To uncover the effects of MDD and ACE on copeptin levels in adult females. Methods: We recruited 94 women (mean age: 34.0 +/- 3.6 years): 23 with MDD and ACE, 24 with MDD without ACE, 22 with ACE without MDD, and 25 healthy controls. ACE was defined as repeated sexual or physical abuse at least once a month over at least one year before the age of 18 years. MDD was defined by the DSM-IV criteria. Copeptin plasma levels were measured with an immunoluminometric assay. Results: The four groups did not differ in demographic variables. We found a significant negative correlation between body mass index (BMI) and copeptin plasma levels (r = -.21; p = .045). Copeptin plasma levels did not differ between the four groups after controlling for BMI. Conclusion: Neither MDD nor ACE was associated with altered plasma copeptin levels. Thus, copeptin does not seem to play a major role in MDD and ACE in adult females

Steroid hormone secretion after stimulation of mineralocorticoid and NMDA receptors and cardiovascular risk in patients with depression

Major depressive disorder (MDD) is associated with altered mineralocorticoid receptor (MR) and glucocorticoid receptor function, and disturbed glutamatergic signaling. Both systems are closely intertwined and likely contribute not only to the pathophysiology of MDD, but also to the increased cardiovascular risk in MDD patients. Less is known about other steroid hormones, such as aldosterone and DHEA-S, and how they affect the glutamatergic system and cardiovascular disease risk in MDD. We examined salivary cortisol, aldosterone, and DHEA-S secretion after stimulation of MR and glutamatergic NMDA receptors in 116 unmedicated depressed patients, and 116 age- and sex-matched healthy controls. Patients (mean age = 34.7 years, SD = ±13.3; 78% women) and controls were randomized to four conditions: (a) control condition (placebo), (b) MR stimulation (0.4 mg fludrocortisone), (c) NMDA stimulation (250 mg D-cycloserine (DCS)), and (d) combined MR/NMDA stimulation (fludrocortisone + DCS). We additionally determined the cardiovascular risk profile in both groups. DCS had no effect on steroid hormone secretion, while cortisol secretion decreased in both fludrocortisone conditions across groups. Independent of condition, MDD patients showed (1) increased cortisol, increased aldosterone, and decreased DHEA-S concentrations, and (2) increased glucose levels and decreased high-density lipoprotein cholesterol levels compared with controls. Depressed patients show profound alterations in several steroid hormone systems that are associated both with MDD pathophysiology and increased cardiovascular risk. Prospective studies should examine whether modulating steroid hormone levels might reduce psychopathology and cardiovascular risk in depressed patients

Cognitive and emotional empathy after stimulation of brain mineralocorticoid and NMDA receptors in patients with major depression and healthy controls

Mineralocorticoid receptors (MR) are predominantly expressed in the hippocampus and prefrontal cortex. Both brain areas are associated with social cognition, which includes cognitive empathy (ability to understand others’ emotions) and emotional empathy (ability to empathize with another person). MR stimulation improves memory and executive functioning in patients with major depressive disorder (MDD) and healthy controls, and leads to glutamate-mediated N-methyl-D-aspartate receptor (NMDA-R) signaling. We examined whether the beneficial effects of MR stimulation can be extended to social cognition (empathy), and whether DCS would have additional beneficial effects. In this double-blind placebo-controlled single-dose study, we randomized 116 unmedicated MDD patients (mean age 34 years, 78% women) and 116 age-, sex-, and education years-matched healthy controls to four conditions: MR stimulation (fludrocortisone (0.4 mg) + placebo), NMDA-R stimulation (placebo + D-cycloserine (250 mg)), MR and NMDA-R stimulation (both drugs), or placebo. Cognitive and emotional empathy were assessed by the Multifaceted Empathy Test. The study was registered on clinicaltrials.gov (NCT03062150). MR stimulation increased cognitive empathy across groups, whereas NMDA-R stimulation decreased cognitive empathy in MDD patients only. Independent of receptor stimulation, cognitive empathy did not differ between groups. Emotional empathy was not affected by MR or NMDA-R stimulation. However, MDD patients showed decreased emotional empathy compared with controls but, according to exploratory analyses, only for positive emotions. We conclude that MR stimulation has beneficial effects on cognitive empathy in MDD patients and healthy controls, whereas NMDA-R stimulation decreased cognitive empathy in MDD patients. It appears that MR rather than NMDA-R are potential treatment targets to modulate cognitive empathy in MDD

Postocclusive Hyperemia Measured with Laser Doppler Flowmetry and Transcutaneous Oxygen Tension in the Diagnosis of Primary Raynaud’s Phenomenon: A Prospective, Controlled Study

The aim of this study was to measure the sensitivity and specificity of transcutaneous oxygen tension and postocclusive hyperemia testing using laser Doppler flowmetry in patients with primary Raynaud’s phenomenon. One hundred patients and one hundred controls were included in the study. Baseline microvascular blood flow and then time to peak flow following occlusion were measured using laser Doppler flowmetry. Afterwards, the transcutaneous oxygen tension was recorded. The sensitivities of baseline microvascular blood flow, postocclusive time to peak flow, and transcutaneous oxygen tension were 79%, 79%, and 77%, respectively. The postocclusive time peak flow had a superior specificity of 90% and area under the curve of 0.92 as compared to 66% and 0.80 for baseline microvascular flow and 64% and 0.76 for transcutaneous oxygen tension. Time to postocclusive peak blood flow measured by laser Doppler flowmetry is a highly accurate test for differentiating patients with primary Raynaud’s phenomenon from healthy controls

Simvastatin add-on to escitalopram in patients with comorbid obesity and major depression (SIMCODE): study protocol of a multicentre, randomised, double-blind, placebo-controlled trial

Introduction: Major depressive disorder (MDD) and obesity are both common disorders associated with significant burden of disease worldwide. Importantly, MDD and obesity often co-occur, with each disorder increasing the risk for developing the other by about 50%-60%. Statins are among the most prescribed medications with well-established safety and efficacy. Statins are recommended in primary prevention of cardiovascular disease, which has been linked to both MDD and obesity. Moreover, statins are promising candidates to treat MDD because a meta-analysis of pilot randomised controlled trials has found antidepressive effects of statins as adjunct therapy to antidepressants. However, no study so far has tested the antidepressive potential of statins in patients with MDD and comorbid obesity. Importantly, this is a difficult-to-treat population that often exhibits a chronic course of MDD and is more likely to be treatment resistant. Thus, in this confirmatory randomised controlled trial, we will determine whether add-on simvastatin to standard antidepressant medication with escitalopram is more efficacious than add-on placebo over 12 weeks in 160 patients with MDD and comorbid obesity. Methods and analysis: This is a protocol for a randomised, placebo-controlled, double-blind multicentre trial with parallel-group design (phase II). One hundred and sixty patients with MDD and comorbid obesity will be randomised 1:1 to simvastatin or placebo as add-on to standard antidepressant medication with escitalopram. The primary outcome is change in the Montgomery-angstrom sberg Depression Rating Scale (MADRS) score from baseline to week 12. Secondary outcomes include MADRS response (defined as 50% MADRS score reduction from baseline), MADRS remission (defined as MADRS score <10), mean change in patients' self-reported Beck Depression Inventory (BDI-II) and mean change in high-density lipoprotein, low-density lipoprotein and total cholesterol from baseline to week 12. Ethics and dissemination: This protocol has been approved by the ethics committee of the federal state of Berlin (Ethik-Kommission des Landes Berlin, reference: 19/0226-EK 11) and by the relevant federal authority (Bundesinstitut fur Arzneimittel und Medizinprodukte (BfArM), reference: 4043387). Study findings will be published in peer-reviewed journals and will be presented at (inter)national conferences

Effekte der Mineralokortikoidrezeptor-Stimulation auf die kognitiven Funktionen bei depressiven und gesunden Probanden

Background: People suffering from major depression often show impaired cognitive function while cortisol secretion is increased. Being predominantly expressed in the hippocampus and prefrontal cortex, mineralocorticoid receptors (MRs) are linked to cognitive function and cortisol inhibition. Therefore, we investigated whether specific fludrocortisone-induced stimulation of MRs 1) improves cognitive functions and 2) decreases cortisol levels in participants with major depression and healthy controls. Methods: In this randomized, double-blind, within-subject, cross-over study design, twenty-four drug-free depressed patients and twenty-four age-, sex- and education-matched healthy controls were treated with either 0.4 mg fludrocortisone or placebo. Cognitive functions were assessed between 2:00 and 5:00 pm; cortisol secretion was measured during cognitive testing using saliva samples. Results: 1) Fludrocortisone-induced stimulation of central MRs improved verbal memory and executive function across groups. No treatment effect on other cognitive domains emerged. In verbal memory and psychomotor speed tests, people with major depression achieved worse results than their healthy counterparts did. 2) Fludrocortisone-induced stimulation of MRs decreased cortisol secretion across groups. We found a significant correlation between cortisol inhibition and verbal memory performance. Conclusions: In conclusion, MR stimulation reveals a possibility to improve cognitive functions in depressed and in healthy participants, which might be partly explained by cortisol inhibition.Hintergrund: Depressive Störungen gehen häufig mit Beeinträchtigungen der kognitiven Leistungsfähigkeit und gesteigerter Kortisolsekretion einher. Zentrale Mineralokortikoidrezeptoren (MR) spielen eine wichtige Rolle bei kognitiven Funktionen und der Regulation des Kortisolhaushalts. Im Gehirn werden MR überwiegend im Hippocampus und im präfrontalen Kortex exprimiert, zwei Hirnareale, die eng mit der kognitiven Leistungsfähigkeit und der Hemmung der Kortisolsekretion assoziiert sind. Wir untersuchten die Effekte von Fludrokortison, einem MR-Agonisten, auf die kognitive Leistungsfähigkeit und Kortisolsekretion. Unsere primäre Fragestellung war, 1) ob durch die Stimulation der MR die kognitiven Funktionen verbessert und 2) die Konzentration des freien Kortisols gesenkt werden können. Methodik: In dieser randomisierten, doppelblinden, intraindividuellen Cross-Over-Studie erhielten 24 unmedizierte depressive und 24 gesunde alters-, geschlechts- und bildungsparallelisierte Probanden 0,4 mg Fludrokortison oder ein Plazebo. Zwischen 14:00 und 17:00 Uhr wurde zum einen die kognitive Leistungsfähigkeit mit Hilfe standardisierter Testverfahren und zum anderen die Kortisolsekretion mittels Speichelproben und anschließender Speichelkortisolbestimmung erfasst. Ergebnisse: 1) Die Fludrokortison-induzierte Stimulation zentraler MR verbesserte die verbale Gedächtnisleistung und die Exekutivfunktionen sowohl bei depressiven Patienten als auch gesunden Kontrollprobanden. Weitere kognitive Domänen wurden durch die MR- Stimulation nicht beeinflusst. Bezüglich der verbalen Gedächtnisleistung und der psychomotorischen Geschwindigkeit erzielten die depressiven Teilnehmer schlechtere Ergebnisse als die gesunden Kontrollprobanden. 2) Die Fludrokortison-induzierte Stimulation zentraler MR reduzierte die Kortisolsekretion sowohl bei depressiven Patienten als auch gesunden Kontrollprobanden. Darüber hinaus bestand über beide Gruppen hinweg eine signifikante Korrelation zwischen der Inhibition der Kortisolsekretion und der verbalen Gedächtnisleistung. Zusammenfassung: Die gezielte Stimulation zentraler MR eröffnet eine neue Möglichkeit zur Verbesserung der kognitiven Funktionen bei depressiven und gesunden Probanden. Dieser Effekt könnte unter anderem auch auf die Absenkung der Kortisolkonzentration zurückgeführt werden

Identifying Important and Difficult Concepts in Introductory Computing Courses using a Delphi Process

A Delphi process is a structured multi-step process that uses a group of experts to achieve a consensus opinion. We present the results of three Delphi processes to identify topics that are important and difficult in each of three introductory computing subjects: discrete math, programming fundamentals, and logic design. The topic rankings can be used to guide both the coverage of student learning assessments (i.e., concept inventories) and can be used by instructors to identify what topics merit emphasis