Asahi-ku, Japan

A Non-interventional Study for Kisqali (Ribociclib) in Combination With an Aromatase Inhibitor for Adjuvant Treatment in Patients With HR+/HER2- Early Breast Cancer at High Risk of Recurrence

This non-interventional study aims to provide information on real-world effectiveness, safety and tolerability, management of adverse events, QoL and patient compliance of patients with HR+/HER2- early breast cancer at high risk of recurrence treated with ribociclib in combination with an non-steroidal aromatase inhibitor (NSAI) ± luteinizing hormone-releasing hormone (LHRH) with curative intent according to the German summary of product characteristics. In order to put the results of patients treated with ribociclib into perspective, socio-economic data, data on QoL and patient compliance will also be collected from patients treated with abemaciclib + endocrine therapy (ET) ± LHRH as described in the respective local summary of product characteristics. To understand reasons for treatment decision, and to analyze the clinical adoption of ribociclib + NSAI ± LHRH after EU approval over time, baseline data will be collected from cohorts of ribociclib + NSAI ± LHRH, abemaciclib + ET ± LHRH, and additionally from patients treated with ET monotherapy ± LHRH and analyzed cross-sectionally. The study is planned to be rolled out into a broad set of German and optionally Austrian and Swiss breast centers and gynecological practices to describe clinical routine in a representative subset of the local healthcare eco-system. It will gather insights into the potential benefits and risks associated with ribociclib + NSAI ± LHRH in the adjuvant treatment of HR+/HER2- eBC patients at high risk of recurrence. This knowledge will inform about clinical decision-making and contribute to improved patient outcomes in routine practice.

Prevention of Mental Disorders Through Self-efficacy Interventions

Low self-efficacy is a transdiagnostic risk factor for several mental disorders. Self-efficacy refers to one's belief that one is capable of performing a behavior necessary to successfully complete a task or achieve a goal. Consistent with theoretical models and empirical findings, individuals with low self-efficacy are more likely to perceive challenges as uncontrollable and threatening and thus are at increased risk for developing mental disorders during sensitive periods such as young adulthood. Self-efficacy interventions have been shown to be effective in promoting health behavior change, quality of life, and treatment adherence in patients with serious illnesses, as well as motivation and performance in students and employees. However, whether targeted self-efficacy training can prospectively prevent the onset of full-threshold anxiety, affective, and substance use disorders in young adults at increased risk for psychopathology remains an open question. The aim of this randomized controlled trial is to test whether a brief cognitive-behavioral intervention in young adults with low self-efficacy can increase general self-efficacy (primary outcome of intervention effectiveness) and thus prevent the onset of DSM-5 mental disorders in the subsequent year (primary outcome of prevention effectiveness). In addition, the investigators examine whether improvements in domain-specific self-efficacy lead to subsequent improvements in general self-efficacy and thus to lower psychopathological symptoms (spillover effects). Young adults (18-30 years) with low self-efficacy but no mental disorder will be included (N=378). The study will include screening, entry, baseline, post, and 12-month follow-up assessments plus additional course assessments in both groups. After the baseline assessment, participants will be randomized to an intervention or control group. The intervention group will receive group-based self-efficacy training (6 sessions of 75-90 minutes each). The control group will also meet in groups (6 sessions) but will only talk about psychological research findings unrelated to self-efficacy or cognitive-behavioral interventions without receiving any training. DSM-5 mental disorders will be assessed at study entry and follow-up with a structured diagnostic interview. Other outcomes will be assessed with established scales and ecological momentary assessments (EMA) at baseline, post and follow-up. Clinical outcomes include psychopathological symptoms (dimensional scores for anxiety, depression, anger, and somatic symptoms, as well as sleep disturbance) and mental disorders (DSM-5 categorical diagnoses of anxiety, affective, and substance use disorders). Intervention effectiveness will be tested using logistic/linear regression and multilevel analyses. Spillover effects between improvements in domain-specific/general self-efficacy and psychopathological symptoms over the course of the study will be examined using cross-lagged panel models. Detailed Description Based on previous research, it is plausible that self-efficacy training may have positive mental health effects and thus successfully prevent the development of mental disorders over time: Consistent with social cognitive theory, self-efficacy training may reduce feelings of anxiety and thus reduce the risk of anxiety disorders. According to the theory of learned helplessness, self-efficacy training may reduce feelings of helplessness and depression and thus reduce the risk of affective disorders. In addition, and consistent with the self-medication hypothesis, individuals who receive self-efficacy training may be less likely to use tobacco, alcohol, or medication/illicit drugs to avoid or down-regulate unpleasant feelings, thereby reducing the risk of substance use disorders. However, although self-efficacy interventions have been shown to be beneficial in other domains, it remains unclear whether self-efficacy training can effectively prevent the onset of full-threshold anxiety, affective, and substance use disorders in young adults. Given that selective and indicated prevention has been shown to be particularly effective in high-risk samples young adults with low self-efficacy and thus increased risk for mental disorders may benefit from targeted self-efficacy training. Study aims This randomized controlled trial in young adults (aged 18-30 years) with low self-efficacy but no 12-month mental disorder at study entry aims to test whether a short cognitive-behavioral intervention in young adults with low levels of self-efficacy (but no 12-month anxiety, affective, or substance use disorder, current intervention (seeking) or suicidality) can effectively increase self-efficacy and thus prospectively prevent the onset of DSM-5 anxiety, affective, and substance use disorders in the subsequent year. The following hypotheses will be tested (based on screening, entry, baseline, post, and 12-month follow-up assessments plus additional course assessments in both groups: Hypotheses 1. Participants in the intervention vs. control group experience a greater increase in general self-efficacy from baseline to post (primary outcome of intervention effectiveness) and greater improvements in dimensional psychopathological symptoms and other dimensional outcome measures from baseline to post (secondary outcome of intervention effectiveness). Note: Other dimensional outcome measures include self-esteem, perceived control, social support, coping strategies, interpersonal competence, work engagement, and individual work performance. 2. Participants in the intervention vs. control group experience a lower risk of incident DSM-5 mental disorders from entry to follow-up (primary outcome of prevention effectiveness) and greater improvements in dimensional psychopathological symptoms and other dimensional outcome measures from baseline to follow-up (secondary outcomes of prevention effectiveness). Note: Not only binary diagnoses but also dimensional symptoms will be assessed to be able to examine more nuanced symptom changes as well as lagged effects between changes in self-efficacy and changes in mental health over time. 3. In the intervention group, improvements in domain-specific self-efficacy will lead to subsequent improvements in general self-efficacy over the course of the intervention (i.e., week 1-6 of the training; spillover hypothesis 1). Note: In the intervention group, participants choose to work on their self-efficacy in the domains of health, social relationships, or education/work. In these analyses, domain-specific self-efficacy refers to the domain that the particular participant works on during the intervention. The selected domains are recorded systemically. 4. In the intervention group, improvements in general self-efficacy will lead to subsequent improvements in dimensional symptom outcomes over the course of the study (i.e., from baseline to follow-up; spillover hypothesis 2). Design The investigators will conduct a randomized controlled trial (in young adults aged 18-30 years with low levels of general self-efficacy but no 12-month anxiety, affective, or substance use disorder, current intervention (seeking), or suicidality with an intervention group and a control group. Participants in the intervention group will receive group-based self-efficacy training (8-12 participants per group; 6 sessions of 75-90 minutes each). Participants in the control group will also meet in groups (8-12 participants per group; 6 sessions) but will only talk about psychological research findings unrelated to self-efficacy or cognitive-behavioral interventions without receiving any training. The design contains three measurement points at which the main outcome variables self-efficacy and psychopathology are assessed: 1) a baseline assessment - immediately before the courses; 2) a post-assessment - immediately after the courses; 3) a 12-month follow-up assessment - 12 months after the post-assessment. Procedure Individuals who meet the inclusion criteria will participate in the baseline assessment. After the baseline assessment, participants will be randomized to either the intervention or control group. Before each course session (6 times), both general and domain-specific self-efficacy will be assessed. Dimensional clinical outcomes will be measured at baseline, post-intervention, and at a 12-month follow-up. Additionally, a one-week EMA will be administered at these three time points. The intervention will be delivered in an online group format (subgroups of 8-12 participants; 6 sessions of 75-90 minutes each) and led by a psychologist. The courses will be structured according to well-established self-efficacy interventions with proven effectiveness, targeting Bandura's 4 key sources of self-efficacy (i.e., mastery experience, vicarious experience, verbal persuasion, and physiological/emotional arousal). Course sessions will be structured as follows: Opening, brief reflection on current progress toward the goal, discussion of homework (with special emphasis on participants' progress and sharing of experiences), introduction to the topic, supervised practice, answering open questions, and closing. Course sessions will be accompanied by weekly homework assignments for practice at home. Assignments will be prepared and discussed during each class session. Participants will also be asked to keep a homework and success diary (workbook) to document changes in thoughts, feelings and behaviors, questions/difficulties (to be discussed in the next session), and accumulating successes in daily life over time (to enhance vicarious experiences). To increase adherence to the intervention, participants will receive a weekly text message with homework reminders and motivational support. Participants in the intervention group will be able to contact a psychologist between sessions to ask questions and receive additional support regarding the intervention and homework. The intervention will be tested in a pilot phase in which self-efficacy will be measured before, during, and after the intervention. In addition, feedback interviews on the intervention will be conducted during the pilot phase to assess its acceptability, and the intervention will be modified accordingly if needed. Recruitment Participants will be recruited through personal contact and print/online advertisements in universities and vocational schools, businesses, coworking spaces, clubs, bars, cafes, restaurants, cinemas, theaters, fitness centers and sports clubs, pharmacies, general practitioners, health insurance companies, and public and social media. Recruitment sites will also include social and welfare institutions that cater to individuals from diverse backgrounds (e.g., low education or migration) to ensure an inclusive sample and to counteract common biases in intervention research (e.g., overrepresentation of highly educated groups). Participants will be recruited not only in Berlin and Potsdam, but also in other (metropolitan and rural) regions of Germany and via online media. Inclusion and exclusion criteria are listed below. After the baseline examination, individuals who meet the inclusion criteria will participate in the baseline examination. After the baseline assessment, they will be randomized to the intervention or control group (balanced randomization [1:1 ratio] based on computer-generated permutated blocks). Participants in the intervention group are required not to receive any other psychological or psychopharmacological intervention at study entry and during the training. Participants in the control group are required not to receive any psychological or psychopharmacological intervention at study entry. However, they may or may not engage in any intervention over the study course (usual care). After completion of the study, they will have the opportunity to receive the same self-efficacy training as the intervention group. Sample size calculations are based on the "weakest line" in the analyses: Any incident or recurrent mental disorder from entry to follow-up assessment in the intervention vs. control group. Calculations are based on data from the baseline and first follow-up assessment of the Early Developmental Stages of Psychopathology Study, a population-based study of adolescents and young adults from Germany. Based on meta-analytic evidence on indicated mental health prevention, the investigators expect the intervention group to improve from standardized self-efficacy scores below -1 to scores between -1 and -0.5. In the EDSP, 21% of those with baseline scores between -1 and -0.5 (~ intervention group) and 41% of those with baseline scores below -1 (~ control group) developed any incident anxiety, affective, or substance use disorder until follow-up (considering only individuals without psychopathology at baseline). With a statistical power of 0.9 and a dropout rate of 20% (from baseline to post and from post to follow-up, respectively), an incidence rate of 21% vs. 41% in the intervention vs. control group yields 189 individuals required per group at baseline (total N=378). Because a 12-month follow-up period is a relatively short time frame to evidence group differences in onset rates of full-threshold mental disorders, also incident/recurrent sub-threshold disorders will be considered. Sub-threshold disorders are defined as disorders falling short of one diagnostic criterion (e.g., the time criterion). In these analyses, incidences of sub-threshold disorders not being present at the entry assessment will be additionally counted. Data Exclusion/Missing Data To ensure response accuracy and validity, several control items will be embedded in the assessments. Observations will be excluded if accuracy scores are too low. Full information maximum likelihood estimation and, if necessary, other imputation methods (e.g., multiple imputation) will be used to deal with missing data. Analysis Data analyses will be performed using RStudio, Python, Stata, and Mplus. Data from the main assessment will be analyzed using linear (dimensional outcomes) and logistic (binary outcomes) regressions. To test whether outcome changes from baseline to post/follow-up vary by group, the difference in the respective outcome score (post/follow-up minus baseline) will be regressed on a group dummy (0=control, 1=intervention). To test whether the rates of incident/recurrent mental disorders from study entry to follow-up vary by group, the diagnostic outcome will be regressed on the group dummy. To test for clinically significant effects, changes in clinical features (e.g., symptom burden and impairment) due to the intervention will be additionally assessed using linear/logistic regressions. EMA data will be analyzed using multilevel analyses with measurement occasions (level 1) nested within persons (level 2). To test whether outcome changes from baseline to post/follow-up vary by group, the respective outcome will be simultaneously regressed on a time dummy (0=baseline, 1=post/follow-up), a group dummy (0=control, 1=intervention), and an interaction term (time*group). Furthermore, multilevel models will be used to capture time-lagged associations between contextual factors and outcome changes in daily life. For example, the effect of daily hassles on momentary fluctuations in state self-efficacy and psychopathological symptoms in the intervention vs. control group will be examined. Dimensional outcomes with non-normally distributed residuals will be log-transformed (log(x+1)). To allow for comparisons across different measures and groups, all dimensional outcomes will be standardized (M=0, SD=1) based on the pooled standard deviation in the intervention and control groups at baseline (to account for potential baseline group differences). Analyses will be adjusted for gender and age. The alpha level will be set at .05. The "BY" method will be used to correct for multiple testing of dependent hypotheses. Spillover effects will be tested using multilevel models with time-lagged effects. If the power requirements are met random intercept cross-lagged panel models will be used. As a manipulation check, the investigators will test whether participants of the intervention group first increase in the domain of self-efficacy they work on (health, social relationships, or education/work) but not in the other domains. For example, individuals working on their health-related self-efficacy are expected to first increase in their health-related self-efficacy but not in the other 2 domains.

A Study of Bempedoic Acid in Combination With Ezetimibe and Either Rosuvastatin or Atorvastatin in Patients With Primary Hypercholesterolemia or Mixed Dyslipidemia

The aim of the current study is to evaluate the effectiveness and safety of bempedoic acid combined with ezetimibe and either atorvastatin or rosuvastatin (hereafter defined as triple therapy) in a real-world clinical setting. No drug will be administered during this observational study. The primary objective of the study is to evaluate the effectiveness of the triple therapy in terms of LDL-C reduction at 8 weeks. The secondary objectives will include the following: - Goal attainment at 8 weeks and 1 year after start of triple therapy - Effectiveness of triple therapy in terms of LDL-C reduction at 1 year - Effectiveness of adding bempedoic acid to statin and ezetimbe at 8 weeks and 1 year - Effectiveness of adding bempedoic acid/ezetimibe FDC to statin in terms of LDL-C reduction at 8 weeks and 1 year - Changes in laboratory values at 8 weeks and 1 year after start of triple therapy - Adherence to triple therapy treatment - Collection and recording of all adverse events occurred since initiation of triple therapy - MACE-3 and MACE-4 (consisting of non-fatal MI, non-fatal stroke, CV-death, and coronary revascularization (for MACE-4 only)) during the year of follow-up - Treatment changes at LMT initiation and at triple therapy initiation - Treatment pathway from triple therapy initiation to 1-year after start of triple therapy

Revumenib in Combination With Azacitidine + Venetoclax in Patients NPM1-mutated or KMT2A-rearranged AML

Exogenous Ketones and Behavior

This study investigates the effects of exogenous ketone ester on behavior, cognition, and metabolism over one week of consumption. Using a within-subjects, randomized, crossover design, participants will undergo two phases: one with the ketone ester supplement and one with a calorie- and taste-matched placebo. The study includes four lab visits: visits 1 and 3 mark the first day of each intervention, while visits 2 and 4 mark the last day. During each visit, participants will complete behavioral tasks, questionnaires, and blood tests. Additionally, participants will record their food intake via an app and collect stool samples throughout the intervention.

European Larynx Organ Preservation Study (ELOS) [MK-3475-C44]

ELOS is a prospective, randomized, open-label, controlled, two-armed parallel group, phase II multicentre trial in local advanced stage III, IVA/B head and neck squamous cell carcinoma of the larynx or hypopharynx (LHNSCC) with PD-L1-expression within tumor tissue biopsy, calculated as CPS ≥ 1 curable by total laryngectomy. Induction chemotherapy (IC) with Docetaxel and Cisplatin (TP) followed by radiation will be compared to additional PD-1 inhibition. Patients will be selected after short induction early response evaluation after the first cycle IC (IC-1) aiming on larynx organ-preservation by additional 2 cycles IC followed by radiotherapy (69.6 Gy) for responders achieving endoscopic estimated tumor surface shrinkage (ETSS) ≥ 30%. Nonresponders (ETSS < 30% or progressing disease) will receive total laryngectomy and selective neck dissection followed by postoperative radiation or chemoradiation according to the recommendation of the clinics multidisciplinary tumor board. However, Patients randomized into the intervention arm starting day 1 will receive 200 mg Pembrolizumab (MK-3475) i.v. in 3-week cycle (q3w) for 17 cycles (12 months). Treatment with pembrolizumab will continue in the experimental arm regardless of ETSS status after IC-1 in both responders and laryngectomized nonresponders, independent from subsequent decision on adjuvant therapy after TL. The primary objective of ELOS is to compare laryngectomy-free survival (LFS) achieved by adding KEYTRUDA® (pembrolizumab) to standard treatment and LFS after standard treatment according to the DeLOS-II protocol in advanced LHNSCC curable by laryngectomy. Hypothesis: Adding PD-1 inhibition by pembrolizumab to organ-preservation chemoradiation treatment improves laryngectomy-free survival (LFS) compared to standard treatment according to the DeLOS-II protocol. The secondary objectives are to compare Quality of Swallowing (QoS) assessed by FEES, event free survival (EFS) and overall survival (OS) achieved by adding KEYTRUDA® (pembrolizumab) to standard treatment and QoS, EFS and OS after standard treatment according to the DeLOS-II protocol in advanced LHNSCC. In general, the main interest in trials focusing on improving quality and degree of larynx organ preservation is late functional (in particular "swallowing") outcome. Current instruments assessing hrQoL are less meaningful than direct objective assessment of swallowing utilizing physical examination like FEES. FEES is a well approved and reliable method and allows clear scoring of quality of swallowing for instance by applying the Rosenbek Scale. Therefore, the investigators decided to avoid any questionnaires for this assessment including those approved for use in head and neck cancer, as they fail to specifically address the main study outcome, functional larynx organ preservation. Hypothesis: Adding PD-1 inhibition by KEYTRUDA® (pembrolizumab) to organ-preservation chemoradiation treatment improves QoS, EFS and OS compared to standard treatment according to the DeLOS-II protocol. EFS events are defined as any event either in interfering with proper larynx organ function (independent of the cause, tumor- or treatment related), relapse (local, loco-regional, or distant), or death.

Equity Evaluation of Fact Boxes on Informed COVID-19 and Influenza Vaccination Decisions - Study Protocol

Background Evidence-based health information (EBHI) and decision aids (DA) are key components for improving health care by enabling more people to make informed decisions. However, despite their overall effectiveness, there is a risk that only certain groups of the population will benefit from them. Because although they are target group oriented, the factors that lead to inequality in terms of shared and informed decision-making have not yet been sufficiently taken into account in their development process. For example, there are many patient-oriented materials written at an advanced level, which makes the materials less accessible to people with reading difficulties, lower education, health literacy or socioeconomic status (SES). Evidence-based fact boxes have been shown to support informed decision-making. However, few studies have analysed how the boxes support decision-making in different social groups. Further, it is unclear whether fact boxes promote informed and shared decision making equally when implemented by health educators (HE) in different settings. Hence, there is a risk that fact boxes will only help less disadvantaged people to make informed health decisions. Objective In a Multi-center, cluster-randomised, cross-sectional study, the effectiveness of evidence-based fact boxes (intervention) compared with usual health education/care (control) on outcomes relevant to the decision to vaccinate will be investigated in people from different backgrounds in Germany. Fact boxes on COVID-19 and influenza vaccination have been adapted in several steps to meet the information needs and requirements of the population. This included feedback from various public health stakeholders on a COVID-19 fact box implemented in Germany in January 2021 by a national Public Health institute, the identification of information needs and requirements of the population in Germany based on secondary data analyses, and testing of COVID-19 fact boxes in pre-studies in population-wide surveys with N=1,942 to N=6,056 respondents in Germany. The data basis and individual studies have been described in detail elsewhere. The Influenza vaccination fact box was updated in 2021 based on current evidence and is available on the Harding Center website for older people (65 years and older) and for people aged 16 to 65. During cognitive interviews, simplified COVID-19 and Influenza vaccination fact boxes were first piloted with German-speaking laypeople and adapted based on their feedback. Visualized COVID-19 fact boxes were also piloted with Arabic-, Turkish- and Russian-speaking laypeople from disadvantaged neighbourhoods in Berlin. A visualized flu fact box is currently being piloted by the University of Erfurt with German-speaking lay people. Main research question Do disadvantaged people benefit to the same extent as non-disadvantaged people in terms of informed and shared decision-making from receiving COVID-19 and influenza vaccination fact boxes as opposed to standard vaccination communication in medical practices and outreach work (field settings)? Research questions (RQ) and main hypotheses (HYP) RQ1 Is the use of fact boxes more effective than standard vaccine communication (control condition) in the field? Primary HYP 1. Compared to standard vaccine communication, fact boxes will lead to higher vaccination knowledge. 2. Compared to standard vaccine communication, fact boxes will lead to more vaccination intentions that are in line with attitudes and vaccination knowledge (informed vaccination intentions; operationalised based on the multidimensional construct of informed choice by Marteau et al. 2001). Secondary HYP 1. Compared to standard vaccine communication, fact boxes will improve risk perception. 2. Compared to standard vaccine communication, fact boxes will increase patient involvement in medical decision making. 3. Compared to standard vaccine communication, fact boxes will decrease decisional conflict. RQ2 Are fact boxes as effective for people with disadvantaging factors as for those without factors associated with disadvantages? Primary HYP Compared to standard vaccine communication, fact boxes will lead to a greater alignment of knowledge, informed vaccination intentions, and accuracy of risk perception between: 1. People with low and high education through fact boxes compared to usual care. 2. People with problematic or inadequate and excellent or sufficient level of health literacy through fact boxes compared to usual care. 3. Non-native (Arabic, Turkish and Russian speaking participants, only with low German skills) and native German speakers (including non-native speakers with high German skills), because the investigators not only provide information in the native language, but also tested it with these target groups. 4. People with low and high reading literacy in different languages, because fact boxes are a complexity-reduced format of health information and the investigators tried to address accessibility through pilot testing with different groups. RQ3 Does the use of fact boxes in outreach work promote more shared and informed decision-making than in regular health care settings? HYP a) Compared to standard vaccine communication fact boxes will more likely lead to more informed vaccination intentions and shared decisions in outreach work than in regular health care settings. Explorative analyses 1. The investigators will analyse the effect of fact boxes on knowledge, vaccination intentions, accuracy of risk perception between people with low and medium or high SSS through fact boxes compared to usual care. 2. The investigators will analyse the effect of fact boxes on vaccination intentions, knowledge, risk perception, patient involvement, and decisional conflict among people with migration-related indicators (e.g., residential status, length of stay in Germany) compared to usual care, controlling for other factors describing the social situation (e.g., education, health literacy).

Emotions, Dopamine, Brain and Body

A Study to Investigate LDL-cholesterol Lowering With Inclisiran Compared to Bempedoic Acid in Patients With Atherosclerotic Cardiovascular Disease.

During the screening period study eligibility will be assessed and the participants' individual LDL-C target according to guideline (Mach et al., 2020) will be determined. Among other criteria, at screening, a participant must be on a stable maximally tolerated dose of a HI statin with either atorvastatin ≥40 mg once a day (QD) or rosuvastatin ≥20 mg QD (+/- Ezetimibe [10mg]) for ≥ 4 weeks with which, however, a target LDL-C of < 70 mg/dL is not reached. During the open-label treatment period, all participants, who fulfill the inclusion/exclusion criteria, will be randomized at V1 (Day 1) in a 1:1 open-label fashion to either Inclisiran sodium 300 mg s.c. (administered at Day 1 and Day 90) or to BPA tablets 180 mg p.o. (given once daily). Participants will be required to maintain their background lipid-lowering treatment (maximally tolerated statin dose +/- Ezetimibe) unchanged for the duration of the study. The end of treatment (EOT) is reached at day 150. A Safety-Follow-up call will be conducted 30 days after EOT visit (Day 180). The overall study duration is approximately 190 days but can vary depending on individual screening and the visit windows allowed for the treatment period and EOS visit.

Real-world Study on Dapagliflozin Usage in Patients With Heart Failure (HF) in Germany