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Through a series of empirical studies involving native speakers of English, German, and Chinese, this paper reveals that the predicate "true" is inherently ambiguous in the empirical domain. Truth statements such as "It is true that Tom is at the party" seem to be ambivalent between two readings. On the first reading, the statement means "Reality is such that Tom is at the party." On the second reading, the statement means "According to what X believes, Tom is at the party." While there appear to exist some cross-cultural differences in the interpretation of the statements, the overall findings robustly indicate that "true" has multiple meanings in the realm of empirical matters., (© The Author(s) 2024.)

Missing transverse momentum is a crucial observable for physics at hadron colliders, being the only constraint on the kinematics of "invisible" objects such as neutrinos and hypothetical dark matter particles. Computing missing transverse momentum at the highest possible precision, particularly in experiments at the energy frontier, can be a challenging procedure due to ambiguities in the distribution of energy and momentum between many reconstructed particle candidates. This paper describes a novel solution for efficiently encoding information required for the computation of missing transverse momentum given arbitrary selection criteria for the constituent reconstructed objects. Pileup suppression using information from both the calorimeter and the inner detector is an integral component of the reconstruction procedure. Energy calibration and systematic variations are naturally supported. Following this strategy, the ATLAS Collaboration has been able to optimise the use of missing transverse momentum in diverse analyses throughout Runs 2 and 3 of the Large Hadron Collider and for future analyses., Competing Interests: Competing InterestsThe authors declare no competing interests., (© The Author(s) 2024.)

Older adults are an underserved population with a broad-spectrum of care needs due to multi-morbidity, including increasing rates of mental health conditions. Though a prime target for tele-behavioral health due to access barriers, older adults face a persistent digital divide that necessitates clinician training and education to ensure interprofessional tele-behavioral health is tailored to their needs. This paper presents findings from a simulation learning program designed to teach students about the role of video telehealth with populations with diverse needs. Occupational therapy (OT) students enrolled in a Master's program between 2017 and 2018 conducted a simulated video telehealth session geared for an older adult. Sessions were recorded and annotated by students, who then provided feedback on their experience of the simulation via reflective essays ( N = 27). Essays were analyzed using conventional content analysis with themes revealing the benefits of simulation in providing students with an opportunity to experience the often unpredictable nature of video telehealth. Themes also revealed perceived limitations of video and the negative impact of age-related conditions and age itself on older adults' ability to engage in video, reflecting ageist stereotyping and bias as potential barriers to novice practitioners' integration of video telehealth with older adults. Simulation provides students an opportunity to engage in active learning and problem-solving in the moment, fostering students' development of clinical reasoning while promoting reflective practice. Findings reveal the importance of supporting students' recognition of biased attitudes to ensure equitable application of tele-behavioral health care, especially to populations with complex needs., Competing Interests: Competing Interests The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. The authors have no relevant financial or non-financial interests to disclose.

The International CTAD Task Force (TF) addressed challenges related to designing clinical trials for agitation in dementia, presenting accomplishments from the two previous TFs on neuropsychiatric symptoms (NPS). In addition, this TF proposed a paradigm shift in NPS assessment and management, presenting Mild Behavioral Impairment (MBI) as a clinical syndrome. MBI is marked by later-life emergent and persistent NPS in dementia-free older persons (ranging from cognitively unimpaired to subjective cognitive decline to mild cognitive impairment), which facilitates earlier detection and better prognostication of Alzheimer's disease (AD). The TF has made the following recommendations for incorporation of NPS into AD preventative trials: (1) clinical trials targeting improvement in MBI symptoms should be undertaken; (2) treatment trials for MBI should be disease specific and confirm the diagnosis of participants using biomarkers; trials should include measures sensitive to cognitive changes in preclinical AD, which can serve as outcome measures, in addition to changes in biomarker levels; (3) as a first step, pharmacotherapeutic trials should address the full MBI complex as well as the specific symptoms/domains that constitute MBI; (4) clinical trials using problem-adaptation psychotherapy to target affective MBI should be considered; and (5) MBI should be considered in AD trials of disease modifying therapies. The well-validated and widely-used MBI Checklist (MBI-C) is an appropriate symptom rating scale for these studies, as it was developed specifically to identify and measure MBI in dementia-free persons. Other scales such as the Neuropsychiatric Inventory (NPI) may be used, although administration at two timepoints may be necessary to operationalize the MBI criterion of symptom persistence., Competing Interests: The Task Force was partially funded by registration fees from industrial participants. These corporations placed no restrictions on this work. MS has served on advisory boards/consultancies Acadia, Otsuka, Avanir, Medesis Pharma, Servier, Eisai, Roche, Biogen, Lilly and Ethypharm. PBR has received research grants from the National Institutes of Aging, Alzheimer’s Clinical Trials Consortium, Richman Family Precision Medicine Center of Excellence on Alzheimer’s Disease, Eisai, Functional Neuromodulation, and Lilly; honoraria from GLG, Leerink, Cerevel, Cerevance, Bioxcel, Sunovion, Acadia, Medalink, Novo Nordisk, Noble Insights, TwoLabs, Otsuka, Lundbeck, Acadia, MedaCorp, ExpertConnect, HMP Global, Synaptogenix, and Neurology Week. CL has received support from Functional Neuromodulation, Ltd, Orion, Servier, Astellas, SVB Leerink, Roche, Avanir, Karuna, Maplight,Axsome, GW Research Limited, Merck, EXCIVA GmbH, Otsuka, and IntraCellular Therapies. DM is a full-time employee of Signant Health. MC has no disclosures. BV is an investigator in clinical trials sponsored by Biogen, Lilly, Roche, Eisai, Pfizer, Pierre Fabre Pharmaceuticals and the Toulouse University Hospital. He has served as SAB member for Biogen, Alzheon, Green Valley, Norvo Nordisk, Longeveron, Rejuvenate Biomed Clinical Pfizer, Eisai France, Advisory Board Meeting - but received no personal compensation. He has served as consultant and/or SAB member for Roche, Lilly, Eisai, TauX, Cerecin with personal compensation. CB has Grants and personal fees from Acadia, Lundbeck, Synexus, Novo Nordisk, and Enterin; and personal fees from Janssen, GW Pharma, TauRx, Biogen, Orion, Roche, Otsuka, Novartis, Eli Lilly, Suven, Sunovion, ADDEX and Exciva. SG has been a member of SAB for Alzheon, AmyriAD, Eisai Canada, EnigmaUSA, Lilly Canada, Medesis, Otsuka Canada, and TauRx, and has given lectures for Biogen Canada, and Lundbeck Korea. ZI has served on advisory boards/consultancies for Acadia, Biogen, Lundbeck, Otsuka, Roche, and the Canadian Agencies for Drugs and Technologies in Health and serves on the Government of Canada Ministerial Advisory Board for Dementia. He has received honoraria from Lundbeck/Otsuka and his institution has received fees from Acadia, Biogen, and Roche in lieu.

The growing prevalence and burden of Alzheimer's disease has catalysed huge investments in research on its causes, diagnosis, treatment and care. After many high-profile failures, recent clinical trials of anti-amyloid drugs have marked a turning point for the field, leading to the approval of the first disease-modifying therapies for Alzheimer's disease by the FDA. It is now up to European regulators to determine whether there is sufficient evidence to approve these drugs for patients with mild cognitive impairment or mild dementia due to Alzheimer's disease. Here, we outline Alzheimer Europe's position on anti-amyloid therapies for Alzheimer's disease, which was adopted by the Board of Alzheimer Europe following consultations with our member associations and with the European Working Group of People with Dementia. Beyond questions of drug efficacy, safety and cost, we highlight important issues that must be addressed by industry, regulators, payers, healthcare systems and governments, to ensure that patients have timely, appropriate and equitable access to innovative treatments, regardless of their socio-economic background, insurance status, or place of residence. We also call for continued investment in research on treatments that might benefit people with more advanced Alzheimer's disease - as well as support and care services that can help people live well with dementia at all stages of the disease., Competing Interests: Angela Bradshaw and Jean Georges are employees of Alzheimer Europe, which has received grants from the European Union’s Health, Horizon Europe and Citizens, Equality, Rights and Values programme (CERV) programmes, the Innovative Health Initiative, the Joint Programme for Neurodegenerative Disease Research (JPND) and the Luxembourg Fonds National de la Recherche, as well as sponsorship and support from AbbVie, Biogen, Eisai, Essity, Fujirebio, GE Healthcare, Grifols, Janssen, Lilly, MSD, Novo Nordisk, Nutricia, Prothena, Roche and TauRx.

Special flood hazard areas (SFHAs), defined as having an annual probability of occurrence of 1 percent or above, are used by U.S. Federal Emergency Management Agency (FEMA) to demarcate areas within which flood insurance purchase is required to secure a mortgage. However, quantifying flood risk within SFHAs can be challenging due to the lack of modeled flood depth data for all return periods. To address this issue, this research quantifies flood risk indicated by average annual loss (AAL) within the A Zone-the subset of the SFHA where wave heights can potentially range from 0 to 3 feet. The methodology resolves the Gumbel quantile function for four distinct flooding cases (i.e., locations flooded at return periods exceeding 1.58-, 10-, 25-, and 50-year return period events) and generates synthetic flood hazard parameters for these cases within the 100-year floodplain, as well as with additional elevation above the base flood elevation (BFE), known as freeboard, for single-family homes with different attributes. The results indicate that for single-family homes in the A Zone, with the lowest floor elevated to the BFE, the AAL ranges from 0.3 to 1 percent of the building replacement cost value. Adding one foot of freeboard reduces flood risk by over 90% if the annual flood risk is between the minimum and 25th percentiles and the 100-year flood depth is less than two feet. The demonstrated approach helps enhance flood resilience in the A Zone, demonstrating the feasibility of proactive measures to protect communities., Supplementary Information: The online version contains supplementary material available at 10.1007/s41742-024-00577-7., Competing Interests: Conflict of InterestThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024.)

Bayesian Dynamic Borrowing (BDB) designs are being increasingly used in clinical drug development. These methods offer a mathematically rigorous and robust approach to increase efficiency and strengthen evidence by integrating existing trial data into a new clinical trial. The regulatory acceptability of BDB is evolving and varies between and within regulatory agencies. This paper describes how BDB can be used to design a new randomised clinical trial including external data to supplement the planned sample size and discusses key considerations related to data re-use and BDB in drug development programs. A case-study illustrating the planning and evaluation of a BDB approach to support registration of a new medicine with the Center for Drug Evaluation in China will be presented. Key steps and considerations for the use of BDB will be discussed and evaluated, including how to decide whether it is appropriate to borrow external data, which external data can be re-used, the weight to put on the external data and how to decide if the new study has successfully demonstrated treatment benefit., (© 2023. The Author(s).)

Given progressive developments and demands on clinical trials, accurate enrollment timeline forecasting is increasingly crucial for both strategic decision-making and trial execution excellence. Naïve approach assumes flat rates on enrollment using average of historical data, while traditional statistical approach applies simple Poisson-Gamma model using time-invariant rates for site activation and subject recruitment. Both of them are lack of non-trivial factors such as time and location. We propose a novel two-segment statistical approach based on Quasi-Poisson regression for subject accrual rate and Poisson process for subject enrollment and site activation. The input study-level data are publicly accessible and it can be integrated with historical study data from user's organization to prospectively predict enrollment timeline. The new framework is neat and accurate compared to preceding works. We validate the performance of our proposed enrollment model and compare the results with other frameworks on 7 curated studies., (© 2023. The Author(s), under exclusive licence to The Drug Information Association, Inc.)