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We introduce detailed numerical modelling of the fast neutral particles inside the duct of a new neutral beam injector (NBI) recently installed at the COMPASS tokamak (major radius R 0 = 0.56 m , vessel midplane minor radius a = 0.23 m , toroidal field B t = 0.9â€"2.1  T ). This new NBI system is able to deliver 1 M W power to the plasma at nominal injection energy of 80 k e V . Collisions with the background neutrals inside the beam duct give birth to fast ions according to the density of the gas and tabulated cross-sections. The ion trajectories are then computed in the complete 3D magnetic field, showing the importance of the stray magnetic field and the magnitude of the field within the gap in between toroidal coils.During the experimental campaign dedicated to the new 1 MW NBI, the beam duct heating was measured by a row of thermocouples located on the top-half of the beam duct. The fast ions collisions with the duct wall cause a local temperature increase with a characteristic pattern. In COMPASS, the location of the fast ions power deposition measured experimentally is in qualitative agreement with modelling of ion losses when following them after the re-ionization process. We trace back the details of the orbits corresponding to deposition at the hot-spot inside the beam duct. Quantitative comparison between the experiment and the simulation shows that a larger than expected amount of neutral gas was inside the duct and this study will guide the design of the future NBI duct in COMPASS Upgrade. [ABSTRACT FROM AUTHOR]

The COMPASS upgrade tokamak (Panek et al 2017 Fusion Eng. Des. 123 11–16) will be a tokamak of major radius R0 = 0.894 m with the possibility to reach high field (Bt ∼ 5 T) and high current (Ip ∼ 2 MA). The machine should see its first plasma in 2023 and H-mode plasma will be obtained from 2025. The main auxiliary heating system used to access H-mode will be 4 MW of neutral beam injection (NBI) power. The NBI will have a nominal injection energy of 80 keV, a maximum injection radius Rtan = 0.65 m and will create a population of well-confined energetic D ions. In this contribution, our modelling studies the NBI deposition and losses when a significant edge background density of neutrals is assumed. We follow the fast ions in the 3D field generated by the 16 toroidal field (TF) coils using the upgraded EBdyna orbit solver (Jaulmes et al 2014 Nucl. Fusion 54 104013). We have implemented a Coulomb collision operator similar to that of NUBEAM (Goldston et al 1981 J. Comput. Phys. 43 61) and a charge-exchange operator that follows neutrals and allows for multiple re-ionizations. Detailed integrated modelling with the METIS code (Artaud et al 2018 Nucl. Fusion 58 105001) yields the pressure and current profiles for various sets of achievable engineering parameters. The FIESTA code (Cunningham 2013 Fusion Eng. Des. 88 3238–3247) calculates the equilibrium and a Biot–Savart solver is used to calculate the intensity of the perturbation induced by the TF coils. Initial distributions of the NBI born fast ions are obtained from the newly developed NUR code, based on Suzuki et al (1998 Plasma Phys. Control. Fusion 40 2097). We evolve the NBI ions during the complete thermalization process and we calculate the amount of NBI ions loss in the edge region due to neutralizations. Results indicate the NBI losses for various injection geometries, various engineering parameters and various assumptions on the magnitude of the background neutral densities. [ABSTRACT FROM AUTHOR]

Measurements using a recently installed edge fast-ion D-alpha (FIDA) diagnostic at the ASDEX Upgrade tokamak show a clear effect of edge localised modes (ELMs) on the passive FIDA signals. While a reduction in the passive FIDA emission is observed in the scrape-off layer (SOL) region, measurements close to the last closed flux surface show an increase in signals shortly after ELMs, followed by a decrease. The decrease provides a clear sign of fast-ion losses in the SOL, while the increase can be explained by an enhanced neutral density during ELMs inside the plasma. In addition, small ELMs are observed, which barely change the neutral density and plasma position but still cause significant changes in the passive FIDA signals. A comparison of the measurements with forward modelling shows that 60% to 80% of the fast ions are lost by ELMs outside the last closed flux surface. In addition, a 20% decrease of the fast-ion density in a range up to 4 cm within the last closed flux surface can be inferred. This range agrees well with the latest modelling results of ELMs using the non-linear MHD code JOREK and shows that less than 0.3% of all fast ions are lost by ELMs. [ABSTRACT FROM AUTHOR]

Here we present a new method that allows the determination of background neutral density profiles based on measurements from neutral particle analyzers (NPA). Bayesian optimization is used to obtain a reliable 5-parameter representation of the inferred profiles. The method has been benchmarked using forward modelling from FIDASIM against measured data. The systematic errors coming from assumptions made in the analysis were evaluated and they are lower than ≲5%. The new method has been tested using data from the ASDEX Upgrade tokamak. When using reconstructed neutral density profiles, good agreement is found between the measured NPA fluxes of neutralized fast ions with predictions based on TRANSP and FIDASIM. Moreover, a clear drop of neutral density is observed at the plasma boundary after edge localized mode (ELM) activity. As suggested by KN1D simulations, this drop is mainly due to an increase of scrape-off layer (SOL) ionization rate, resulting from higher SOL plasma densities and temperatures after the ELM crash. Moreover, the new method allows calculating the local plasma ionization source which will be important for future transport studies. [ABSTRACT FROM AUTHOR]

Presents a numerical scheme for efficient integration of the bidomain model of action potential propagation in cardiac tissue. Description of the bidomain model; Numerical issues; Computations.

Objective ImPACT Pediatric is a neurocognitive test used to assess concussion in children ages 5–11. Embedded in the test is a series of yes/no symptom questions, answered by both parents and their child. The purpose of this study was to determine if there was any utility in creating summary scores using child- and parent-reported symptoms, and document agreement between child- and parent-reported symptoms. Method De-identified baseline and post-concussion ImPACT Pediatric data were obtained from the lead programmer at ImPACT Applications, Inc, who was blind to the purpose of the study. Number of symptoms endorsed through parent and child self-report was documented by summing individual symptoms endorsed at baseline and within 7 days of concussion. Chi-squared analyses were conducted to evaluate the level of agreement between the four symptoms that appear on both child and parent symptom lists (Headache, Dizziness, Tiredness, and Nausea/Vomiting). Results Across the four shared symptoms (Headache, Dizziness, Tiredness, and Nausea/Vomiting), parent- child co-endorsement ranged from 27%–71% at baseline, and 69%–95% post-concussion; Kappa (as a measure of agreement) was weak;.24–.41. Paired-samples T-tests revealed children report significantly more symptoms than their parents at baseline (p < .001) but not post-concussion (p = .14). Conclusions Parents and their children are not in agreement with respect to symptom endorsement on the ImPACT Pediatric at baseline, with children endorsing a significantly greater number of total symptoms. While the presence/absence of specific symptoms may be of clinical utility, creating a summary symptom score out of binary symptom data does not appear to be useful. [ABSTRACT FROM AUTHOR]

Purpose The literature on altitude and concussions in football shows some evidence of protective effects of living and training and playing at high altitudes. We explored the likelihood of sustaining concussions within the AFC West division, specifically comparing games hosted at high altitude in Denver versus games hosted by at low altitudes in Los Angeles, Oakland, and Kansas City. Methods Information was recorded for all regular season AFC West division games (N= 42) occurring in the 2012–2018 seasons. Altitude for each stadium was calculated using DaftLogic's Google Sandbox. Concussion incidence for the 2012–2018 seasons was collected from PBS Frontline's Concussion-Watch and weekly injury reports (NFL.com). Chi-square analyses compared likelihood of: concussions occurring in High Altitude versus Low Altitude, a Broncos player sustaining a concussion in High Altitude versus Low Altitude, and a non-Broncos AFC West player sustain a concussion in High Altitude versus Low Altitude. Results Chi-square analyses revealed no greater likelihood of players sustaining concussions in High Altitude versus Low Altitude (p=.35), or of Broncos (p=1.00) or non-Broncos (p=.47) AFC West players sustaining concussions in High Altitude versus Low Altitude. Conclusion Altitude is not a significant factor for increased likelihood of concussions, and popular theories such as "the mile-high effect" are not supported by the data. We found no evidence for the proposed protective factor of living and training at high altitude for Broncos team members, as they showed an equal likelihood of sustaining a concussion at high and low altitude. [ABSTRACT FROM AUTHOR]

Purpose The "replication crisis" in psychology and across the broader field of social sciences raises criticism due to a lack of data to show that esoteric research findings can be replicated. The present study replicated and validated the two-factor "memory" and "speed" structure of ImPACT (Schatz & Maerlender, 2013). Methods High school aged athletes (N=18,918, Mean age=15.4, SD=1.2) who completed pre-season baseline ImPACT testing were randomly assigned to one of 5 independent samples of approximately 3,780 athletes. Exploratory factor analyses (FA) for a two-factor solution were conducted with ImPACT composite scores within each of the five groups. Post-Concussion Symptom Scale (PCSS) scores were included, with the expectation they would load on a third, unique factor. Results All five samples met assumptions for FA (KMO Measure of Sampling Adequacy above.600), and all five analyses yielded the same "memory" and "speed" two-factor structure. Visual Motor Speed and Reaction Time loaded on the first "Speed" factor and Verbal and Visual Memory loaded on a second "Memory" factor. The PCSS scores loaded on a third, unique "symptom" factor. Conclusion Replication of the two-factor structure for ImPACT in a five large high school sample further validates the model. Given that both visual and verbal memory involve encoding of information presented visually, use of a "memory" factor may improve interpretation of ImPACT scores. Similarly, similarities between constructs measuring speed of responding (Reaction Time) and speed of processing (Visual Motor Processing Speed) may be best explained using a "speed" factor. [ABSTRACT FROM AUTHOR]

Objective: Prior studies demonstrate that some untoward clinical outcomes vary by outdoor temperature. This is true of some endpoints common among persons with diabetes, a population vulnerable to climate change-associated health risks. Yet, prior work has been agnostic to the antidiabetes drugs taken by such persons. We examined whether relationships between ambient temperature and adverse health outcomes among persons with type 2 diabetes (T2D) varied by exposure to different antidiabetes drugs., Design: Retrospective cohort., Setting: Healthcare and meteorological data from five US states, 1999-2010., Participants: US Medicaid beneficiaries with T2D categorised by use of antidiabetes drugs., Exposure: Maximum daily ambient temperature (t-max)., Outcomes: Hospital presentation for serious hypoglycaemia, diabetic ketoacidosis (DKA) or sudden cardiac arrest (examined separately)., Methods: We linked US Medicaid to US Department of Commerce data that permitted us to follow individuals longitudinally and examine health plan enrolment, healthcare claims, and meteorological exposures-all at the person-day level. We mapped daily temperature from weather stations to Zone Improvement Plan (ZIP) codes, then assigned a t-max to each person-day based on the residential ZIP code. Among prespecified subcohorts of users of different pharmacologic classes of antidiabetes drugs, we calculated age and sex-adjusted occurrence rates for each outcome by t-max stratum. We used modified Poisson regression to assess relationships between linear and quadratic t-max terms and each outcome. We examined effect modification between t-max and a covariable for current exposure to a specific antidiabetes drug and assessed significance via Wald tests., Results: We identified ∼3 million persons with T2D among whom 713 464 used sulfonylureas (SUs), dipeptidyl peptidase-4 inhibitors (DPP-4is), meglitinides, or glucagon-like peptide 1 receptor agonists (GLP1RAs). We identified a positive linear association between t-max and serious hypoglycaemia among non-insulin users of glimepiride and of glyburide but not glipizide (Wald p value for interaction among SUs=0.048). We identified an inverse linear association between t-max and DKA among users of the DPP-4i sitagliptin (p=0.016) but not the GLP1RA exenatide (p=0.080). We did not identify associations between t-max and sudden cardiac arrest among users of SUs, meglitinides, exenatide, or DPP-4is., Conclusions: We identified some antidiabetes drug class-specific and agent-specific differences in the relationship between ambient temperature and untoward glycaemic but not arrhythmogenic, safety outcomes., Competing Interests: Competing interests: CEL is a Special Government Employee of the US Food and Drug Administration. CEL consults for Novo Nordisk and TriNetX. CEL recently received an honorarium from the American College of Clinical Pharmacy Foundation, University of Florida and Ancora Education. CEL’s spouse is employed by Merck; neither CEL nor his spouse own Merck stock. WB serves on multiple independent data monitoring committees for Genentech. MB has consulted for Clinique and ToxiMap. MB has received honoraria from the US Environmental Protection Agency, National Institutes of Health, Health Canada, Colorado School of Public Health, Duke University, University of Texas, Data4Justice, Korea University, Organization of Teratology Information Specialists, University of Pennsylvania, Boston University, IOP Publishing, Pacific-10 Conference, UK Research and Innovation, AXA Research Fund, Harvard University, SciQuest and University of Montana. MB has received travel support from the Colorado School of Public Health, University of Texas, Duke University, Boston University, University of Pennsylvania, Harvard University, American Journal of Public Health, Columbia University, CMAS conference and Nature conference. SH has consulted for the Medullary Thyroid Cancer Consortium (Novo Nordisk, AstraZeneca Pharmaceuticals LP, Eli Lilly and Company), Urovant Sciences, Bluebird Bio, Amylyx Pharmaceuticals, Ipsen Bioscience, Covis Pharma GmbH, i2o Therapeutics, Basilea, Balance Ophthalmics, Lykos Therapeutics and Applied Therapeutics. Other authors report no conflicts., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In a prior screening study, saxagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4i), was found to have an increased rate of serious bleeding when used concomitantly with several oral anticoagulants (OACs). We aimed to confirm or refute the associations between concomitant use of individual OACs and DPP-4is and serious bleeding in a large US database, using self-controlled case series (SCCS) and case-crossover (CCO) designs. The study population was eligible Medicare beneficiaries co-exposed to a DPP-4i (precipitant) and either an OAC (object drug) or lisinopril (negative control object drug) in 2016-2020. For the SCCS, we used conditional Poisson regression to estimate adjusted rate ratios (RRs) between each co-exposure (vs. not) and serious bleeding and divided the RR by the adjusted RR for the corresponding lisinopril + precipitant pair to obtain ratios of RRs (RRRs). For the CCO, we estimated the adjusted odds ratios (ORs) of exposure to the precipitant in the focal window vs. referent window using multivariable conditional logistic regression and divided the ORs in the object drug-exposed cases over the ORs in negative object drug-exposed cases to obtain the ratios of ORs (RORs). The adjusted RRRs for serious bleeding ranged from 0.32 (0.05-1.91) for apixaban/lisinopril + saxagliptin to 3.49 (1.29-9.48) for warfarin/lisinopril + linagliptin. The adjusted RORs ranged from 0.01 (0.00-0.20) for rivaroxaban/lisinopril + saxagliptin to 2.99 (0.74-12.11) for apixaban/lisinopril + linagliptin. While we could not confirm previously identified signals because of statistical imprecision, several numerically elevated estimates still warrant caution in concomitant use and further examination., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Negative affectivity of caregivers has been linked to difficulties in the caregiver-patient relationship and it is assumed to contribute to the maintenance of eating disorder (ED) symptoms., Aims: The present study investigated the relationship of patients' ED symptom severity to patients' and caregivers' depressive symptoms, and caregivers' involvement in a mixed sample of adult inpatients with anorexia (AN) and bulimia nervosa (BN), as well as their caregivers., Method: The Eating Disorder Examination and Beck Depression Inventory (BDI) were administered to 55 adult ED patients (26 AN and 29 BN), and the BDI as well as the Involvement Evaluation Questionnaire were filled in by one caregiver of each patient., Results: Our results showed caregivers' depressive symptoms to be significantly related to patients' ED symptom severity, however depressive symptoms and ED symptoms of patients were not related. No connection of involvement of caregivers and ED severity of patients was found. AN and BN patients did not significantly differ on ED severity or depressive symptoms. Caregivers of AN and BN patients did not differ significantly on depressive symptoms and involvement., Conclusions: Our results support the importance of mental health support for caregivers of adults with AN and BN.

Purpose: This study aimed to examine the most important problems and needs caregivers of adult inpatients with eating disorders (EDs) are confronted with in their everyday lives. A further aim was to investigate the associations between problems, needs, involvement, and depression in carers., Methods: Fifty-five caregivers of inpatients with EDs (26 anorexia nervosa, 29 bulimia nervosa) completed the Carers' Needs Assessment, Beck Depression Inventory, and the Involvement Evaluation Questionnaire. The relationships between variables were tested via multiple linear regressions and mediation analyses., Results: The most frequent problem reported by caregivers was a lack of information about the course and treatment of the illness and consequent disappointment, whereas their most frequently reported needs were different forms of information and counselling. Problems, unmet needs, and worrying were especially high in parents compared to other caregivers. Involvement mediated significantly between problems (b = 0.26, BCa CI [0.03, 0.49]) as well as unmet needs (b = 0.32, BCa CI [0.03, 0.59]) of caregivers and their depressive symptoms., Conclusion: Our findings underline the importance of including the problems and needs of caregivers of adult eating disorder patients in the planning of family and community interventions, to support their mental health., Level of Evidence: Level III: Evidence obtained from cohort or case-control analytic studies., (© 2023. The Author(s).)

Background: Patients who require psychiatric inpatient treatment early in life are a particularly at-risk population. Factors such as adverse childhood experiences (ACEs) are, however, not well studied in those requiring psychiatric inpatient treatment during both childhood or adolescence and adulthood. Thus, the aim of the current study was to investigate, in young adult inpatients, the risk factors for prior admissions in Child and Adolescent Psychiatry, with a focus on ACEs., Materials and Methods: An explorative population-based systematic chart investigation of psychiatric inpatients aged 18-25 was conducted at the University Hospital Tulln, Austria. Data analysis was done with descriptive methods and Pearson's chi- squared-, Fisher's exact-, Mann-Whitney- U -tests and predictive logistic regression models., Results: The sample comprised 390 inpatients (51.8% female), with an average age of 20 years at first psychiatric hospital admission. Those with a former child and adolescent psychiatry inpatient treatment (10.3%) were predominantly female (77.5%). Their number of documented ACEs was increased compared to those without former child and adolescent psychiatry admissions (2 vs 1.1), with up to twice as many experiences of family dysfunction, neglect or abuse. Sexual abuse (OR: 3.0), having been an adopted or fostered child (OR: 4.5), and female sex (OR: 3.0) were identified as main risk factors. Furthermore, former child and adolescent psychiatry inpatients suffered from higher rates of psychosomatic or personality disorders, comorbidities and functional impairment, and were readmitted twice as often in young adulthood., Conclusion: Young adult inpatients with reoccurring psychiatric inpatient treatments have increased rates of severe ACEs. Thus, special attention should be given to identifying ACEs, evaluating needs for psychosocial support and therapy, and meeting these needs after discharge., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fellinger, Knasmüller, Kocsis-Bogar, Wippel, Fragner, Mairhofer, Hochgatterer and Aigner.)

Objective: To investigate factors associated with collegiate athletes' beliefs regarding chronic traumatic encephalopathy (CTE) mechanism., Design: Cross-sectional study., Methods: A total of 838 collegiate athletes (61.9% men) from seven institutions completed a 10-minute survey that captured information relative to demographics, diagnosed concussion history, formal sport-related concussion education, additional sources of concussion information, and beliefs about multiple concussions and premature return-to-play following a head impact as mechanisms for CTE., Results: More than half of collegiate athletes believed that multiple concussions (58.2%) and premature return-to-play (59.1%) may cause CTE. Those who reported getting concussion information from sports news had higher odds of believing multiple concussions and premature return-to-play were CTE mechanisms compared to those who did not get information from sports news sources. Additionally, CTE mechanism beliefs were significantly greater in collegiate athletes who were male, had sustained a previous diagnosed concussion, or had acquired concussion information from the NCAA., Conclusions: Sports news' reporting of CTE storylines, which highlight former male athletes with complex brain injury histories, may influence collegiate athletes' beliefs about concussion. Therefore, it is recommended that concussion awareness initiatives incorporate information related specifically to CTE to empower collegiate athletes with evidence-based, patient-oriented information and knowledge regarding this condition.

This study tested the hypothesis that chronic depression (CD) is more similar to depression with multiple prior episodes (ME) than to depression with few prior episodes (FE). Data from participants (n = 1013) with mild to moderate depressive symptoms (Patient Health Questionnaire [PHQ-9] score 5 - 14) who took part in a randomized control trial of an internet intervention for depression (EVIDENT trial) were re-analyzed. The MINI-interview was conducted to diagnose CD (n = 376). If CD was not diagnosed, the self-reported number of depressive episodes was used to categorize participants as having episodic depression with up to five (FE, n = 422) or more than five (ME, n = 215) prior episodes. Over a three-year period, participants were assessed repeatedly regarding the course of depression (PHQ-9, QIDS), quality of life (SF-12) and therapeutic progress (FEP-2). At baseline, most scores were different between CD and FE but comparable between CD and ME. Time to remission did not differ between CD and ME but was longer in CD compared to FE. Results suggest that ME closely resembles CD and that CD differs from FE., Competing Interests: Declaration of Competing Interests JPK received payments for presentations and publications by the following companies: Beltz, Hogrefe, Elsevier. BM is employed as research director at GAIA AG, the company that developed, owns, and operates the internet intervention investigated in this trial. All the other authors report no relationships with commercial interests., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The initial preference task (IPT) is an implicit measure that has featured prominently in the literature and enjoys high popularity because it offers to provide an unobtrusive and objective assessment of self-esteem that is easy to administer. However, its use for self-esteem assessment may be limited because of weak associations with direct personality measures. Moreover, moderator effects of sample- and study-related variables need investigation to determine the value of IPT-based assessments of self-esteem., Methods: Conventional and grey-literature database searches, as well as screening of reference lists of obtained articles, yielded a total of 105 independent healthy adult samples (N = 17,777) originating from 60 studies. Summary effect estimates and subgroup analyses for potential effect moderators (e.g., administration order, algorithm, rating type) were calculated by means of meta-analytic random- and mixed-effects models. Moreover, we accounted for potential influences of publication year, publication status (published vs. not), and participant sex in a weighted stepwise hierarchical multiple meta-regression. We tested for dissemination bias through six methods., Results: There was no noteworthy correlation between IPT-based implicit and explicit self-esteem (r = .102), indicating conceptual independence of these two constructs. Effects were stronger when the B-algorithm was used for calculation of IPT-scores and the IPT was administered only once, whilst all other moderators did not show significant influences. Regression analyses revealed a somewhat stronger (albeit non-significant) effect for men. Moreover, there was no evidence for dissemination bias or a decline effect, although effects from published studies were numerically somewhat stronger than unpublished effects., Discussion: We show that there is no noteworthy association between IPT-based implicit and explicit self-esteem, which is broadly consistent with dual-process models of implicit and explicit evaluations on the one hand, but also casts doubt on the suitability of the IPT for the assessment of implicit self-esteem on the other hand., Competing Interests: The authors have declared that no competing interests exist.

The evaluation of a series of aminoisoindoles as β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors and the discovery of a clinical candidate drug for Alzheimer's disease, (S)-32 (AZD3839), are described. The improvement in permeability properties by the introduction of fluorine adjacent to the amidine moiety, resulting in in vivo brain reduction of Aβ40, is discussed. Due to the basic nature of these compounds, they displayed affinity for the human ether-a-go-go related gene (hERG) ion channel. Different ways to reduce hERG inhibition and increase hERG margins for this series are described, culminating in (S)-16 and (R)-41 showing large in vitro margins with BACE1 cell IC(50) values of 8.6 and 0.16 nM, respectively, and hERG IC(50) values of 16 and 2.8 μM, respectively. Several compounds were advanced into pharmacodynamic studies and demonstrated significant reduction of β-amyloid peptides in mouse brain following oral dosing.

Amino-2H-imidazoles are described as a new class of BACE-1 inhibitors for the treatment of Alzheimer's disease. Synthetic methods, crystal structures, and structure-activity relationships for target activity, permeability, and hERG activity are reported and discussed. Compound (S)-1m was one of the most promising compounds in this report, with high potency in the cellular assay and a good overall profile. When guinea pigs were treated with compound (S)-1m, a concentration and time dependent decrease in Aβ40 and Aβ42 levels in plasma, brain, and CSF was observed. The maximum reduction of brain Aβ was 40-50%, 1.5 h after oral dosing (100 μmol/kg). The results presented highlight the potential of this new class of BACE-1 inhibitors with good target potency and with low effect on hERG, in combination with a fair CNS exposure in vivo.