An Estimate of the Isopycnal Diffusion Tensor Based on Particle Statistics

The quality of eddy ux-gradient parametrizations in models with coarse resolution depends on whether the generated diffusivity is similar to that of reference solutions produced by eddy resolving models. It is therefore essential to accurately describe the transport properties of eddy resolving ocean models. This thesis is a survey of the lateral transport of passive tracers induced by mesoscale eddies in the velocity field of a 1/12° numerical model of the North Atlantic. Statistical tools are used to relate particle trajectories of Lagrangian floats to the effective eddy diffusivity: Both Taylor's theory of turbulent dispersion, which forms the foundation for the analysis, and further refinements thereof, are discussed and used for computations. The underlying theories rely on several restrictive assumptions about the statistics of the flow field, and one objective of this thesis is to make the reader aware of how difficult an interpretation of the results can be

Involvement of UDP-Glucuronosyltransferases and Sulfotransferases in the Excretion and Tissue Distribution of Resveratrol in Mice.

Resveratrol is a naturally occurring polyphenolic compound with various pharmacological activities. It is unknown whether the expression of metabolizing enzymes correlates with resveratrol levels in organs and tissues. Therefore, we investigated the metabolism and tissue distribution of resveratrol in mice and assessed its association with the expression of UDP-glucuronosyltransferase (Ugt) and sulfotransferase (Sult) genes. Plasma, urine, feces, and various organs were analyzed using high-performance liquid chromatography at up to 8 h after intragastric resveratrol administration. The metabolism of resveratrol was pronounced, leading to the formation of resveratrol glucuronides and sulfates. Concentrations of resveratrol and its metabolites were high in the gastrointestinal organs, urine, and feces, but low in the liver and kidneys. In lung, heart, thymus, and brain tissues, parent resveratrol levels exceeded the sulfate and glucuronide concentrations. The formation of resveratrol conjugates correlated with the expression of certain Ugt and Sult genes. Reverse transcription quantitative PCR (RT-qPCR) analysis revealed high mRNA expression of Ugt1a1 and Ugt1a6a in the liver, duodenum, jejunum, ileum, and colon, leading to high concentrations of resveratrol-3-O-glucuronide in these organs. Strong correlations of resveratrol-3-O-sulfate and resveratrol-3-O-4'-O-disulfate formation with Sult1a1 mRNA expression were also observed, particularly in the liver and colon. In summary, our data revealed organ-specific expression of Sults and Ugts in mice that strongly affects resveratrol concentrations; this may also be predictive in humans following oral uptake of dietary resveratrol

Severe Plasmodium knowlesi infection with multi-organ failure imported to Germany from Thailand/Myanmar

During the last two decades human infections with Plasmodium knowlesi are increasingly diagnosed in South East Asia and have also been reported in travellers. A severe case of imported P. knowlesi infection in a 73-year old German is presented, who had been travelling through Myanmar and Thailand for three weeks. Microscopy showed a parasitaemia of 3% and different parasite stages including band-forms resembling Plasmodium malariae. Due to the clinical picture of severe malaria and the microscopical aspect (combination of parasites resembling P. malariae and Plasmodium falciparum), P. knowlesi was suspected. The patient was treated with intravenous quinine; he was put on mechanical ventilation and catecholamines due to cardiorespiratory failure. Parasitaemia was cleared rapidly but renal function deteriorated resulting in intermittent haemodialysis. The patient was hospitalized for six weeks but he recovered completely without any physical sequelae. Plasmodium knowlesi mono-infection was confirmed by molecular methods later on. Plasmodium knowlesi infection has to be taken into account in feverish travellers returning from Thailand/Myanmar. Moreover this species can cause life-threatening or even lethal complications. Accordingly severe P. knowlesi infection should be treated like severe P. falciparum infections

Cross-sectional, descriptive study of Chagas disease among citizens of Bolivian origin living in Munich, Germany

PURPOSE: Chagas disease (CD) has become a global health issue mainly due to migration. Germany lacks surveillance data and is home to a large Latin American immigrant population. Recognising that Bolivia is the country with the highest CD prevalence in Latin America, this cross-sectional, descriptive pilot study investigated CD and associated factors among citizens of Bolivian origin living in Munich, Germany. METHODS: Participants completed a questionnaire in order to collect socioeconomic and health-related data. In addition, serology was performed. In case of positive serological tests, PCR diagnostic and clinical staging together with disease management was initiated. Qualitative research was conducted to identify personal and community barriers as well as strategies to increase CD awareness among the population at risk. RESULTS: Between June 2013 and June 2014, 43 people from Bolivia (or descendants) were enrolled. A total of 9.3% (4/43), of whom two women were of childbearing age, tested seropositive (ELISA and IFAT), and one also by PCR. For 2/4 positive participants, clinical evaluation was performed and the indeterminate form of CD was diagnosed. Knowledge about CD symptoms and ways of transmission were completely absent among 55.8% (24/43, 2/4 with CD) and 30.2% (13/43, 1/4 with CD) of participants, respectively. A total of 27.9% (12/43, 0/4 with CD) of participants had donated blood prior to the study, whereas 62.8% (27/43, 3/4 with CD) were motivated to donate blood in the future. The qualitative research identified lack of knowledge as well as stigma and fears related to CD. CONCLUSIONS: Despite the small number of participants, the prevalence of CD as well as the potential risk of non-vectorial transmission was alarming. Campaigns adapted for Latin American migrants as well as control strategies should be developed and put in place in order to prevent non-vectorial transmission and actively detect cases of CD in Germany.This study was supported through the Clinical Leave Programme (TI 07.001, grant to MP) and the MD Programme (TI 07.003, grant to MP and MH) by the German Center for Infection Research (DZIF). The University of Munich (LMU) contributed through the programme ‘Lehre@LMU’ (grants to MP and CS), and Mundo Sano provided financial and human resources to plan the informational approach to reach the Bolivian community living in Munich and to design and perform the qualitative research.S

Doctoral Studies as part of an Innovative Training Network (ITN): Early Stage Researcher (ESR) experiences [version 2; peer review: 2 approved]

Background: The Marie-Skłodowska-Curie Actions’ (MSCA) Innovative Training Network (ITN) is a doctoral training programme jointly implemented by academic institutions and industries from countries across Europe and beyond. To our knowledge no study has examined the experience of students participating in MSCA-ITNs. This study aims to evaluate and report MSCA-ITN Early Stage Researcher (ESR) experiences. Methods: The Innovative Training Network - Evaluation Questionnaire (ITN-EQ) was developed to assess supervision, training, collaborations and experiences of ESRs and forwarded to two tinnitus-related ITNs and seven ITNs of other disciplines. Results: Key advantages identified included better career prospects, multidisciplinary research opportunities/collaborations, international exposure, personal/professional development, plus generous salaries and research budgets. However, lack of a common EU framework resulted in the experience being largely dependent on the host institution, country and supervisor. Moreover, managing the dual requirements of ITNs and host institutions while completing a three-year PhD seemed challenging for most ESRs. ESR involvement in workshop and training school planning was desirable. More than 80% of ESRs rated the overall ITN experience favourably and 98.3% would recommend the same to prospective PhD students. Conclusions: This report could provide valuable insights in planning and management of future ITNs and could assist prospective students in their decision of joining an ITN for their PhD

Doctoral Studies as part of an Innovative Training Network (ITN):Early Stage Researcher (ESR) experiences [version 2; peer review: 2 approved]

Background: The Marie-Skłodowska-Curie Actions’ (MSCA) Innovative Training Network (ITN) is a doctoral training programme jointly implemented by academic institutions and industries from countries across Europe and beyond. To our knowledge no study has examined the experience of students participating in MSCA-ITNs. This study aims to evaluate and report MSCA-ITN Early Stage Researcher (ESR) experiences. Methods: The Innovative Training Network - Evaluation Questionnaire (ITN-EQ) was developed to assess supervision, training, collaborations and experiences of ESRs and forwarded to two tinnitus-related ITNs and seven ITNs of other disciplines. Results: Key advantages identified included better career prospects, multidisciplinary research opportunities/collaborations, international exposure, personal/professional development, plus generous salaries and research budgets. However, lack of a common EU framework resulted in the experience being largely dependent on the host institution, country and supervisor. Moreover, managing the dual requirements of ITNs and host institutions while completing a three-year PhD seemed challenging for most ESRs. ESR involvement in workshop and training school planning was desirable. More than 80% of ESRs rated the overall ITN experience favourably and 98.3% would recommend the same to prospective PhD students. Conclusions: This report could provide valuable insights in planning and management of future ITNs and could assist prospective students in their decision of joining an ITN for their PhD

Corrigendum:Multidisciplinary Tinnitus Research: Challenges and Future Directions From the Perspective of Early Stage Researchers (Front. Aging Neurosci., (2021), 13, (647285), 10.3389/fnagi.2021.647285)

In the original article, there was an error. For the sentence “NMDA receptor antagonists (AM-101) have been discontinued in phase III for not meeting endpoints (van de Heyning et al., 2014)” there was a typographical error (phase III should have been phase II). In addition, it was brought to our attention that clinical trials for AM-101 are ongoing. A correction has been made to section 6. Treatment Development, Subsection 6.4. Pharmacology-Based Interventions, paragraph 1. The corrected paragraph is below. A wide variety of therapeutic drugs have been used to relieve tinnitus (Elgoyhen and Langguth, 2010). For acute tinnitus, a dose-dependent reduction in tinnitus intensity was observed with intravenous lidocaine (Trellakis et al., 2006). However, its use is controversial due to its short-lasting response, its potentially life threatening arrhythmogenic side effects, and the low bioavailability of its oral form (Israel et al., 1982; Trellakis et al., 2007; Gil-Gouveia and Goadsby, 2009). A potential goal of pharmacologic tinnitus research could be to identify the mechanism by which lidocaine interferes with tinnitus and mimic this effect using a drug with better tolerance that can be orally administered. For chronic tinnitus, the off-label use of medicines like betahistine (Hall et al., 2018d), anticonvulsants (Hoekstra et al., 2011), and glutamate receptor antagonists have shown little or no effect in clinical trials. Prescription of antidepressants and benzodiazepines is limited to tinnitusassociated comorbidities such as depression, insomnia and anxiety (Langguth et al., 2019). Moreover, three clinical research programs, in the last few years, were discontinued in phase II and III. AMPA antagonist selurampanel (BGG492) has not resulted in a new compound (Cederroth et al., 2018). NMDA receptor antagonists (AM-101) did not meet the primary endpoint of improving minimum masking level in acute tinnitus in a phase II clinical trial but showed improvement for tinnitus loudness, annoyance, sleep difficulties, and tinnitus impact in patients with tinnitus after noise trauma or otitis media (van de Heyning et al., 2014). Many other treatments decreasing tinnitus percept or targeting central auditory processing pathways are at a preclinical phase (Schilder et al., 2019). The modulator of voltage-gated potassium channels (Kv3.1) (AUT00063) was not effective in alleviating tinnitus symptoms (Hall et al., 2019b). The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated

Severe Plasmodium knowlesi infection with multi-organ failure imported to Germany from Thailand/Myanmar

During the last two decades human infections with Plasmodium knowlesi are increasingly diagnosed in South East Asia and have also been reported in travellers. A severe case of imported P. knowlesi infection in a 73-year old German is presented, who had been travelling through Myanmar and Thailand for three weeks. Microscopy showed a parasitaemia of 3% and different parasite stages including band-forms resembling Plasmodium malariae. Due to the clinical picture of severe malaria and the microscopical aspect (combination of parasites resembling P. malariae and Plasmodium falciparum), P. knowlesi was suspected. The patient was treated with intravenous quinine; he was put on mechanical ventilation and catecholamines due to cardiorespiratory failure. Parasitaemia was cleared rapidly but renal function deteriorated resulting in intermittent haemodialysis. The patient was hospitalized for six weeks but he recovered completely without any physical sequelae. Plasmodium knowlesi mono-infection was confirmed by molecular methods later on. Plasmodium knowlesi infection has to be taken into account in feverish travellers returning from Thailand/Myanmar. Moreover this species can cause life-threatening or even lethal complications. Accordingly severe P. knowlesi infection should be treated like severe P. falciparum infections

Standardised profiling for tinnitus research: The European School for Interdisciplinary Tinnitus Research Screening Questionnaire (ESIT-SQ)

Background: The heterogeneity of tinnitus is substantial. Its numerous pathophysiological mechanisms and clinical manifestations have hampered fundamental and treatment research significantly. A decade ago, the Tinnitus Research Initiative introduced the Tinnitus Sample Case History Questionnaire, a case history instrument for standardised collection of information about the characteristics of the tinnitus patient. Since then, a number of studies have been published which characterise individuals and groups using data collected with this questionnaire. However, its use has been restricted to a clinical setting and to the evaluation of people with tinnitus only. In addition, it is limited in the ability to capture relevant comorbidities and evaluate their temporal relationship with tinnitus. Method: Here we present a new case history instrument which is comprehensive in scope and can be answered by people with and without tinnitus alike. This ‘European School for Interdisciplinary Tinnitus Research Screening Questionnaire’ (ESIT-SQ) was developed with specific attention to questions about potential risk factors for tinnitus (including demographics, lifestyle, general medical and otological histories), and tinnitus characteristics (including perceptual characteristics, modulating factors, and associations with co-existing conditions). It was first developed in English, then translated into Dutch, German, Italian, Polish, Spanish, and Swedish, thus having broad applicability and supporting international collaboration. Conclusions: With respect to better understanding tinnitus profiles, we anticipate the ESIT-SQ to be a starting point for comprehensive multi-variate analyses of tinnitus. Data collected with the ESIT-SQ can allow establishment of patterns that distinguish tinnitus from non-tinnitus, and definition of common sets of tinnitus characteristics which might be indicated by the presence of otological or comorbid systemic diseases for which tinnitus is a known symptom