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Abstract Background Molecular profiling of estrogen receptor (ER), progesterone receptor (PR), and ERBB2 (also known as Her2) is essential for breast cancer diagnosis and treatment planning. Nevertheless, current methods rely on the qualitative interpretation of immunohistochemistry and fluorescence in situ hybridization (FISH), which can be costly, time-consuming, and inconsistent. Here we explore the clinical utility of predicting receptor status from digitized hematoxylin and eosin-stained (H&E) slides using machine learning trained and evaluated on a multi-institutional dataset. Methods We developed a deep learning system to predict ER, PR, and ERBB2 statuses from digitized H&E slides and evaluated its utility in three clinical applications: identifying hormone receptor-positive patients, serving as a second-read tool for quality assurance, and addressing intratumor heterogeneity. For development and validation, we collected 19,845 slides from 7,950 patients across six independent cohorts representative of diverse clinical settings. Results Here we show that the system identifies 30.5% of patients as hormone receptor-positive, achieving a specificity of 0.9982 and a positive predictive value of 0.9992, demonstrating its ability to determine eligibility for hormone therapy without immunohistochemistry. By restaining and reassessing samples flagged as potential false negatives, we discover 31 cases of misdiagnosed ER, PR, and ERBB2 statuses. Conclusions These findings demonstrate the utility of the system in diverse clinical settings and its potential to improve breast cancer diagnosis. Given the substantial focus of current guidelines on reducing false negative diagnoses, this study supports the integration of H&E-based machine learning tools into workflows for quality assurance.

We develop a general theory of higher semiadditive Fourier transforms that includes both the classical discrete Fourier transform for finite abelian groups at height $n=0$ , as well as a certain duality for the $E_n$ -(co)homology of $\pi $ -finite spectra, established by Hopkins and Lurie, at heights $n\ge 1$ . We use this theory to generalize said duality in three different directions. First, we extend it from $\mathbb {Z}$ -module spectra to all (suitably finite) spectra and use it to compute the discrepancy spectrum of $E_n$ . Second, we lift it to the telescopic setting by replacing $E_n$ with $T(n)$ -local higher cyclotomic extensions, from which we deduce various results on affineness, Eilenberg–Moore formulas and Galois extensions in the telescopic setting. Third, we categorify their result into an equivalence of two symmetric monoidal $\infty $ -categories of local systems of $K(n)$ -local $E_n$ -modules [-12pc] and relate it to (semiadditive) redshift phenomena. The Great Wave off Kanagawa, Katsushika Hokusai.

The celebrated tenfold way of Altland-Zirnbauer symmetry classes discern any quantum system by its pattern of nonspatial symmetries. It lays at the core of the periodic table of topological insulators and superconductors which provided a complete classification of weakly interacting electrons' noncrystalline topological phases for all symmetry classes. Over recent years, a plethora of topological phenomena with diverse surface states has been discovered in crystalline materials. In this paper, we obtain an exhaustive classification of topologically distinct ground states as well as topological phases with anomalous surface states of crystalline topological insulators and superconductors for key space-groups, layer-groups, and rod-groups. This is done in a unified manner for the full tenfold way of Altland-Zirnbauer nonspatial symmetry classes. We establish a comprehensive paradigm that harnesses the modern mathematical framework of equivariant spectra; it allows us to obtain results applicable to generic topological classification problems. In particular, this paradigm provides efficient computational tools that enable an inherently unified treatment of the full tenfold way.

Policy Points The reinstitution of pre-COVID-19 pandemic licensure regulations has impeded interstate telehealth. This has disproportionately impacted patients who live near a state border; geographically mobile patients, such as college students; and patients with rare diseases who may need care from a specialist outside their state. Several promising and feasible reforms are available, at both state and federal levels, to facilitate interstate telehealth. For example, states can offer exemptions to licensure requirements for certain types of telehealth such as follow-up care or create licensure registries that impose little reduced paperwork and fees on physicians. On the federal level, congressional interventions that mimic the Department of Veterans Affairs Maintaining Internal Systems and Strengthening Integrated Outside Networks (VA MISSION) Act of 2018 can waive provider licensing and geographic restrictions to telehealth within certain federal programs such as Medicare. Any discussion of medical licensure reform, however, must also consider the current political climate, one in which states are taking divergent stances on sensitive topics such as reproductive care, gender-affirming care, and substance use treatments., (© 2024 Milbank Memorial Fund.)

Importance: Interest in administering psychedelic agents as mental health treatment is growing rapidly. As drugmakers invest in developing psychedelic medicines for several psychiatric indications, lawmakers are enacting legal reforms to speed access globally, and health agencies are preparing to approve these treatments. Meanwhile, US states, such as Oregon and Colorado, are making psychedelics available for supervised use outside the conventional health care system., Observations: Despite legal change and potentially imminent regulatory approval in some countries, standards for integrating psychedelics into health care have lagged, including norms for designing and implementing informed consent processes. Informed consent is complicated by the unique features of psychedelics and their means of administration. Because no governments have approved any classic psychedelics for general medical or psychiatric use, only clinical researchers have obtained informed consent from trial participants. Accordingly, there is an unmet need for informed consent processes tailored to the challenges of administering psychedelics in nonresearch settings., Conclusions and Relevance: Analysis of the challenges of designing and implementing psychedelic informed consent practices revealed 7 essential components, including the possibility of short- and long-term perceptual disturbances, potential personality changes and altered metaphysical beliefs, the limited role of reassuring physical touch, the potential for patient abuse or coercion, the role and risks of data collection, relevant practitioner disclosures, and interactive patient education and comprehension assessment. Because publicly available informed consent documents for psychedelic clinical trials often overlook or underemphasize these essential elements, sample language and procedures to fill the gap are proposed.

Globally, more than 1 billion people with disabilities are disproportionately and differentially at risk from the climate crisis. Yet there is a notable absence of climate policy, programming, and research at the intersection of disability and climate change. Advancing climate justice urgently requires accelerated disability-inclusive climate action. We present pivotal research recommendations and guidance to advance disability-inclusive climate research and responses identified by a global interdisciplinary group of experts in disability, climate change, sustainable development, public health, environmental justice, humanitarianism, gender, Indigeneity, mental health, law, and planetary health. Climate-resilient development is a framework for enabling universal sustainable development. Advancing inclusive climate-resilient development requires a disability human rights approach that deepens understanding of how societal choices and actions-characterised by meaningful participation, inclusion, knowledge diversity in decision making, and co-design by and with people with disabilities and their representative organisations-build collective climate resilience benefiting disability communities and society at large while advancing planetary health., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Psychiatry is rapidly adopting digital phenotyping and artificial intelligence/machine learning tools to study mental illness based on tracking participants' locations, online activity, phone and text message usage, heart rate, sleep, physical activity, and more. Existing ethical frameworks for return of individual research results (IRRs) are inadequate to guide researchers for when, if, and how to return this unprecedented number of potentially sensitive results about each participant's real-world behavior. To address this gap, we convened an interdisciplinary expert working group, supported by a National Institute of Mental Health grant. Building on established guidelines and the emerging norm of returning results in participant-centered research, we present a novel framework specific to the ethical, legal, and social implications of returning IRRs in digital phenotyping research. Our framework offers researchers, clinicians, and Institutional Review Boards (IRBs) urgently needed guidance, and the principles developed here in the context of psychiatry will be readily adaptable to other therapeutic areas.

Rapid advances in digital technology have expanded the availability of diagnostic tools beyond traditional medical settings. Previously confined to clinical environments, these many diagnostic capabilities are now accessible outside the clinic. This study utilized the Delphi method, a consensus-building approach, to develop recommendations for the development and deployment of these innovative technologies. The study findings present the 29 consensus-based recommendations generated through the Delphi process, providing valuable insights and guidance for stakeholders involved in the implementation and utilization of these novel diagnostic solutions. These recommendations serve as a roadmap for navigating the complexities of integrating digital diagnostics into healthcare practice outside traditional settings like hospitals and clinics., (© 2024. The Author(s).)

Background: Clinicians and their employers, concerned with privacy and liability, are often hesitant to support the recording of clinical encounters. However, many people wish to record encounters with healthcare professionals. It is therefore important to understand how existing law applies to situations where an individual requests to record a clinical encounter., Methods: We searched for and reviewed relevant legal documents that could apply to recording clinical encounters. We limited the scope by purposefully examining relevant law in nine countries: Australia, Brazil, Canada, France, Germany, India, Mexico, the United Kingdom and the United States. We analyzed legal texts for consents needed to record a conversation, whether laws applied to remote or face-to-face conversations and penalties for violations., Findings: Most jurisdictions have case law or statutes, derived from a constitutional right to privacy, or a wiretapping or eavesdropping statute, governing the recording of private conversations. However, little to no guidance exists on how to translate constitutional principles and case law into advice for people seeking to record their medical encounters., Interpretation: The law has not kept pace with people's wish to record clinical interactions, which has been enabled by the arrival of mobile technology.

May 11, 2023, marked the end of the federal COVID-19 Public Health Emergency (PHE). During the PHE, regulatory flexibilities allowed telehealth to more effectively connect physicians providing care and patients seeking it. This paper discusses the implications of the end of the PHE on telehealth coverage, payment, reimbursement, and licensure, and exposes inconsistencies and inequities in extant state regulations.

The Council of Europe, Europe's most important human rights organization, is developing a legally binding instrument for the development, design, and application of AI systems. This "Convention on Artificial Intelligence, Human Rights, Democracy and the Rule of Law" (AI Convention) aims to protect human rights against the harms of AI. The AI Convention may become the first legally-binding international treaty on AI. In this article, we highlight the implications of the proposed AI Convention for the health and human rights protection of patients. We praise the following characteristics [1]. Global regulation for technology that easily crosses jurisdictions [2]. The human rights-based approach with human rights assessment [3]. The actor-neutral, full-lifecycle approach [4]. The creation of enforceable rights through the European Human Rights Court. We signal the following challenges [1]. The sector-neutral approach [2]. The lack of reflection on new human rights [3]. Definitional issues, and [4] The process of global negotiations. We conclude that it is important for the Council of Europe not to compromise on the wide scope of application and the rights-based character of the proposed AI Convention., Competing Interests: Declaration of Competing Interest Hannah van Kolfschooten has no conflict of interest to declare. Her research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Carmel Shachar has no conflict of interest to declare. Her work was supported by Novo Nordisk Foundation (grant for a Collaborative Research Programme, grant agreement number NNF17SA0027784) and the Gordon and Betty Moore Foundation (grant agreement number 9974)., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Voice-based AI-powered digital assistants, such as Alexa, Siri, and Google Assistant, present an exciting opportunity to translate healthcare from the hospital to the home. But building a digital, medical panopticon can raise many legal and ethical challenges if not designed and implemented thoughtfully. This paper highlights the benefits and explores some of the challenges of using digital assistants to detect early signs of cognitive impairment, focusing on issues such as consent, bycatching, privacy, and regulatory oversight. By using a fictional but plausible near-future hypothetical, we demonstrate why an "ethics-by-design" approach is necessary for consumer-monitoring tools that may be used to identify health concerns for their users., Competing Interests: Declaration of interests I.G.C. reports that he serves as a bioethics consultant for Otsuka on the Abilify MyCite product, is a member of the Illumina and Bayer ethics advisory boards, and serves as an ethics consultant for DawnLight., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflict-of-Interest Disclosures: Jessica Castner discloses receiving grants and fees from the National Institutes of Health, fees from the Emergency Nurses Association, and serving as co-chair of the American Thoracic Society’s Health Policy Committee on Terrorism and Inhalation Disasters section. Barbara Evans discloses receiving grants from the National Institutes of Health. Steven Lin discloses serving as VP of Health Sciences for Codex Health, where he is a paid consultant; and receiving grants administered through Stanford University from Amazon, American Academy of Family Physicians, American Board of Family Medicine, Center for Professionalism and Value in Health Care, DeepScribe, Google Health, Omada Health, Predicta Med, Quadrant Technologies, Soap Health, Society of Teachers of Family Medicine, UCSF, and Verily. Kenneth Mandl discloses that his laboratory receives sponsored research funding from Quest Diagnostics; and that Boston Children’s Hospital receives corporate philanthropic support for his laboratory from SMART Advisory Committee members, which include the American Medical Association, BMJ Group, Eli Lilly and Company, Google Cloud, Hospital Corporation of America, Microsoft, Optum, Cambia Health Solutions, Quest Diagnostics, and Humana. Mark Sendak discloses that he is co-inventor of technology licensed from Duke University to Cohere Med, Inc and Clinetic, Inc.; and that he holds equity in Clinetic, Inc. Carmel Shachar discloses that she is a member of Advarra’s Institutional Research Board.

Once-daily oral tenofovir/emtricitabine is highly effective as pre-exposure prophylaxis (PrEP) against HIV but is dependent on adherence, which may be challenging for men who have sex with men (MSM) and use substances. Digital pill systems (DPS) permit the direct, real-time measurement of adherence, though user perceptions of data privacy in this context are unknown. Thirty prospective DPS users - HIV-negative MSM with non-alcohol substance use - completed in-depth qualitative interviews exploring preferences around privacy, access, and sharing of DPS adherence data. Participants discussed some concerns about the impact of DPS use on personal privacy, and emphasized the need for robust data protections in the technology. Participants were interested in having on-demand access to their adherence data, and were most willing to share data with primary care providers and long-term relationship partners. Future investigations exploring bioethical frameworks around DPS use are warranted, and user preferences should inform best practices for protecting DPS data., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The development of autonomous artificial intelligence (A-AI) products in health care raises novel regulatory challenges, including how to ensure their safety and efficacy in real-world settings. Supplementing a device-centered regulatory scheme with a regulatory scheme that considers A-AI products as a 'physician extender' may improve the real-world monitoring of these technologies and produce other benefits, such as increased access to the services offered by these products. In this article, we review the three approaches to the oversight of nurse practitioners, one type of physician extender, in the USA and extrapolate these approaches to produce a framework for the oversight of A-AI products. Under the framework, the US Food and Drug Administration would evaluate A-AI products and determine whether they are allowed to operate independently of physician oversight; required to operate under some physician oversight via a 'collaborative protocol' model; or required to operate under direct physician oversight via a 'supervisory protocol' model., (© The Author(s) 2022. Published by Oxford University Press on behalf of Duke University School of Law, Harvard Law School, Oxford University Press, and Stanford Law School. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Health technology is advancing at a rapid clip, with many of these technologies appearing on consumer products like smartphones and tablets. Federal regulators have responded to these changes with a flexible approach that allows firms to manufacture a 'general wellness product' ('GWP') without being subject to regulation typically applied to 'devices' that diagnose or treat a disease or condition. Using currently available medical products and devices from across a spectrum of diseases, we describe how firms can use this existing regulatory framework to develop innovative products by 'skating the line' between mostly unregulated GWPs and regulated devices. On the one hand, we find that skating the line offers a variety of benefits, including potential improvements to product development, innovation, and patient access to medical technologies. On the other hand, we show that this technique has potential costs to patient safety, competition, and data sharing. Skating the regulatory line between GWP and devices, in other words, offers important benefits but is not without risks. Any further regulatory action to address such risks should be careful to leave significant unregulated space for product development., (© The Author(s) 2022. Published by Oxford University Press on behalf of Duke University School of Law, Harvard Law School, Oxford University Press, and Stanford Law School. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Digital applications (apps) are commonly used across the research ecosystem. While apps are frequently updated in the course of clinical and behavioral research, there is limited guidance as to when an app update should trigger action related to human research participant protections and who should be responsible for monitoring and reviewing these updates. We term this the "update problem" and argue that, while it is the principal investigator's duty to track all relevant updates, the level of involvement and re-review by the institutional review board (IRB) of an approved research protocol should vary depending on whether the update may be classified as minor, not minor, or significant. Minor updates require at most annual notification of the IRB, updates that are not minor require prompt notification of the IRB, and significant updates may require full board re-review or another response. We also suggest how these policies might be implemented., (© 2022 by The Hastings Center. All rights reserved.)

Employers and governments are interested in the use of serological (antibody) testing to allow people to return to work before there is a vaccine for SARS-CoV-2. We articulate the preconditions needed for the implementation of antibody testing, including the role of the U.S. Food & Drug Administration.

Telehealth has the potential to address health disparities, but not without deliberate choices about how to implement it. To support vulnerable patients, health policy leaders must pursue creative solutions such as public-private partnerships, broadband infrastructure, and value-based payment. Without these initiatives or others like them, health disparities are likely to persist despite telehealth's tantalizing potential.

Competing Interests: Conflict-of-Interest Disclosures: Mark Sendak discloses that his employer holds a license agreement with Cohere Med, Inc. Sanjay Basu discloses that he receives grants from the National Institutes of Health and the Centers for Disease Control and Prevention; that he receives personal fees from the New England Journal of Medicine, PLoS Medicine, Collective Health, and HealthRight360; and that he has a pending patent relative to this work. Shantanu Nundy discloses that he is employed by Accolade, Inc., which provides personalized advocacy and population health services.

There has been increasing interest in the use of home monitoring technologies during the COVID-19 pandemic to decrease interpersonal contacts and the resultant risks of exposure for people to the coronavirus SARS-CoV-2. This Perspective explores how the accelerated development of these technologies also raises major concerns pertaining to safety and privacy. We make recommendations for needed interventions to ensure safety and review best practices and US regulatory requirements for privacy and security. We discuss, among other topics, Emergency Use Authorizations for medical devices and privacy laws of the USA and Europe.