Learning-by-Doing with Spillovers in Competitive Industries, Free Entry, and Regulatory Policy

We study the impact of learning-by-doing with spillovers in competitive markets with free market entry. Within a two period model, we consider first the case where fixed costs are incurred only once, and entry is once and for all. In the second case fixed costs are incurred in each period, and both market exit after the first period and late entry in the second period is possible. For the first case first best allocations can only be decentralized by subsidizing output in the first period and additionally paying an entry premium. If exit and late entry are possible and if market exit by some firms is socially optimal, the optimal policy scheme requires a nonlinear output subsidy which serves to discriminate between exiting and staying firms. We further investigate the comparative statics effects of the different policy instruments. --learning-by-doing,spillovers,regulatory policy

The association between thyroid function biomarkers and attention deficit hyperactivity disorder

The relation between thyroid function biomarkers and attention deficit hyperactivity disorder (ADHD) in children and adolescents is currently unclear. Cross-sectional data from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS Baseline) was analyzed to assess the association between thyroid function biomarkers and ADHD in a population-based, nationally representative sample. The study cohort included 11,588 children and adolescents with 572 and 559 having an ADHD diagnosis or symptoms, respectively. ADHD symptoms were assessed through the Inattention/Hyperactivity subscale of the Strength and Difficulties Questionnaire. ADHD diagnosis was determined by a physician or psychologist. Serum thyroid stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) concentrations were determined enzymatically. Adjusted regression models were used to relate serum TSH, fT3, and fT4 with risk for ADHD diagnosis or symptoms. In children, a 1 mIU/l higher TSH was related to a 10% lower risk (odds ratio [OR] 0.90; 95% confidence interval [CI] 0.81–1.00) of ADHD diagnosis. We found a significant positive association between fT3 and continuously assessed ADHD symptoms in children (β 0.08; 95% CI 0.03–0.14). Our results suggest that physical maturity may influence the association between thyroid function biomarkers and risk for ADHD

Staphylococcal Peptidoglycan Co-Localizes with Nod2 and TLR2 and Activates Innate Immune Response via Both Receptors in Primary Murine Keratinocytes

In mammalian host cells staphylococcal peptidoglycan (PGN) is recognized by Nod2. Whether PGN is also recognized by TLR2 is disputed. Here we carried out PGN co-localization and stimulation studies with TLR2 and Nod2 in wild type and mutant host cells. To exclude contamination with lipoproteins, polymeric staphylococcal PGN (PGNpol) was isolated from Staphylococcus aureus Δlgt (lacking lipidated prelipoproteins). PGNpol was biotinylated (PGN-Bio) for fluorescence monitoring with specific antibodies. Keratinocytes from murine oral epithelium (MK) readily internalized PGN-Bio in an endocytosis-like process. In wt MK, PGNpol induced intracellular accumulation of Nod2 and TLR2 and co-localized with Nod2 and TLR2, but not with TLR4. In TLR2-deficient MK Nod2 and in Nod2-deficient MK TLR2 was induced, indicating that PGNpol recognition by Nod2 is independent of TLR2 and vice versa. In both mutants IL-6 and IL-1B release was decreased by approximately 50% compared to wt MK, suggesting that the immune responses induced by Nod2 and TLR2 are comparable and that the two receptors act additively in MK. In TLR2-tranfected HEK293 cells PGNpol induced NFkB-promoter fused luciferase expression. To support the data, co-localization and signaling studies were carried out with SHL-PGN, a lipase protein covalently tethered to PGN-fragments of varying sizes at its C-terminus. SHL-PGN also co-localized with Nod2 or TLR2 and induced their accumulation, while SHL without PGN did not. The results show that staphylococcal PGN not only co-localizes with Nod2 but also with TLR2. PGN is able to stimulate the immune system via both receptors

Where is the 'global' in the European Union's Health Research and Innovation Agenda?

Global Health has not featured as prominently in the European Union (EU) research agenda in recent years as it did in the first decade of the new millennium, and participation of low-income and middle-income countries (LMICs) in EU health research has declined substantially. The Horizon Europe Research and Innovation Framework adopted by the European Parliament in April 2019 for the period 2021-2027 will serve as an important funding instrument for health research, yet the proposed health research budget to be finalised towards the end of 2019 was reduced from 10% in the current framework, Horizon 2020, to 8% in Horizon Europe. Our analysis takes the evolvement of Horizon Europe from the initial framework of June 2018 to the framework agreed on in April 2019 into account. It shows that despite some improvements in terms of Global Health and reference to the Sustainable Development Goals, European industrial competitiveness continues to play a paramount role, with Global Health research needs and relevant health research for LMICs being only partially addressed. We argue that the globally interconnected nature of health and the transdisciplinary nature of health research need to be fully taken into account and acted on in the new European Research and Innovation Framework. A facilitated global research collaboration through Horizon Europe could ensure that Global Health innovations and solutions benefit all parts of the world including EU countries

From disgusting and complicated to simple and brilliant: Implementation perspectives and lessons learned from users and rejectors of mail-in SARS-CoV-2 gargle tests

BackgroundDespite the important role of testing as a measure against the COVID-19 pandemic, user perspectives on SARS-CoV-2 tests remain scarce, inhibiting an improvement of testing approaches. As the world enters the third year of the pandemic, more nuanced perspectives of testing, and opportunities to expand testing in a feasible and affordable manner merit consideration.MethodsConducted amid the second pandemic wave (late 2020–early 2021) during and after a multi-arm trial evaluating SARS-CoV-2 surveillance strategies in the federal state Baden-Württemberg, Germany, this qualitative sub-study aimed to gain a deeper understanding of how test users and test rejectors perceived mail-in SARS-CoV-2 gargle tests. We conducted 67 semi-structured in-depth interviews (mean duration: 60 min) via telephone or video call. Interviews were audio-recorded, transcribed verbatim and analyzed inductively using thematic analysis. The Consolidated Framework for Implementation Research guided the findings' presentation.ResultsRespondents generally described gargle sampling as simple and comfortable. However, individual perceptions of the testing method and its feasibility varied widely from disgusting and complicated to simple and brilliant. Self-sampling was appreciated for lowering infection risks during testing, but also considered more complex. Gargle-sampling increased participants' self-efficacy to sample correctly. Communication (first contact, quantity and content of information, reminders, support system) and trust (in the study, its institutional affiliation and test method) decisively influenced the intervention's acceptability.ConclusionUser-driven insights on how to streamline testing include: consider communication, first impressions of tests and information as key for successful mail-in testing; pay attention to the role of mutual trust between those taking and administering tests; implement gargle self-sampling as a pleasant alternative to swab testing; offer multiple test methods to increase test up-take

Hamburg's Spaces of Danger: Race, Violence and Memory in a Contemporary Global City

Germany today is experiencing the strongest upsurge of right-wing populism since the second world war, most notably with the rise of Pegida and Alternative für Deutschland. Yet wealthy global cities like Hamburg continue to present themselves as the gatekeepers of liberal progress and cosmopolitan openness. This article argues that Hamburg’s urban boosterism relies on, while simultaneously obscuring, the same structures of racial violence that embolden reactionary movements. Drawing on the work of Walter Benjamin and Allan Pred, we present an archaeology of Hamburg’s landscape, uncovering some of its ‘spaces of danger’––sites layered with histories of violence, many of which lie buried and forgotten. We find that these spaces, when they become visible, threaten to undermine Hamburg’s cosmopolitan narrative. They must, as a result, be continually erased or downplayed in order to secure the city as an attractive site for capital investment. To illustrate this argument, we give three historical examples: Hamburg’s role in the Hanseatic League during the medieval and early modern period; the city under the Nazi regime; and the recent treatment of Black African refugees. The article’s main contribution is to better situate issues of historical landscape, collective memory and racialized violence within the political economy of today’s global city

Sarcoma classification by DNA methylation profiling

Sarcomas are malignant soft tissue and bone tumours affecting adults, adolescents and children. They represent a morphologically heterogeneous class of tumours and some entities lack defining histopathological features. Therefore, the diagnosis of sarcomas is burdened with a high inter-observer variability and misclassification rate. Here, we demonstrate classification of soft tissue and bone tumours using a machine learning classifier algorithm based on array-generated DNA methylation data. This sarcoma classifier is trained using a dataset of 1077 methylation profiles from comprehensively pre-characterized cases comprising 62 tumour methylation classes constituting a broad range of soft tissue and bone sarcoma subtypes across the entire age spectrum. The performance is validated in a cohort of 428 sarcomatous tumours, of which 322 cases were classified by the sarcoma classifier. Our results demonstrate the potential of the DNA methylation-based sarcoma classification for research and future diagnostic applications

Framework and baseline examination of the German National Cohort (NAKO)

The German National Cohort (NAKO) is a multidisciplinary, population-based prospective cohort study that aims to investigate the causes of widespread diseases, identify risk factors and improve early detection and prevention of disease. Specifically, NAKO is designed to identify novel and better characterize established risk and protection factors for the development of cardiovascular diseases, cancer, diabetes, neurodegenerative and psychiatric diseases, musculoskeletal diseases, respiratory and infectious diseases in a random sample of the general population. Between 2014 and 2019, a total of 205,415 men and women aged 19–74 years were recruited and examined in 18 study centres in Germany. The baseline assessment included a face-to-face interview, self-administered questionnaires and a wide range of biomedical examinations. Biomaterials were collected from all participants including serum, EDTA plasma, buffy coats, RNA and erythrocytes, urine, saliva, nasal swabs and stool. In 56,971 participants, an intensified examination programme was implemented. Whole-body 3T magnetic resonance imaging was performed in 30,861 participants on dedicated scanners. NAKO collects follow-up information on incident diseases through a combination of active follow-up using self-report via written questionnaires at 2–3 year intervals and passive follow-up via record linkages. All study participants are invited for re-examinations at the study centres in 4–5 year intervals. Thereby, longitudinal information on changes in risk factor profiles and in vascular, cardiac, metabolic, neurocognitive, pulmonary and sensory function is collected. NAKO is a major resource for population-based epidemiology to identify new and tailored strategies for early detection, prediction, prevention and treatment of major diseases for the next 30 years. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10654-022-00890-5