Alzheimer’s Disease (AD) represents a major and rapidly growing burden to the healthcare ecosystem. A growing body of evidence indicates that cognitive, behavioral, sensory, and motor changes may precede clinical manifestations of AD by several years. Existing tests designed to diagnose neurodegenerative diseases, while well-validated, are often less effective in detecting deviations from normal cognitive decline trajectory in the earliest stages of the disease. In the quest for gold standards for AD assessment, there is a growing interest in the identification of readily accessible digital biomarkers, which harness advances in consumer grade mobile and wearable technologies. Topics examined include a review of existing early clinical manifestations of AD and a path to the respective sensor and mobile/wearable device usage to acquire domain-centric data towards objective, high frequency and passive digital phenotyping.

Tumor hypoxia–driven accumulation of extracellular adenosine was shown to facilitate tumor evasion by engaging the immunosuppressive, intracellular cAMP-elevating A₂ adenosine receptors (A₂R) on tumor-reactive effector T cells, but there remains a need for careful evaluation of the limiting factors and properties of A₂R blockade–enabled antitumor immunity. In studies of A_2AR and/or A_2BR gene–deficient mice, we found that A_2AR deletion—but not A_2BR deletion—liberates endogenous CD8⁺ T cell antitumor immunity against weakly immunogenic MCA205 sarcomas. Studies of adoptively transferred A_2AR^−/−, A_2BR^−/−, or A_2AR^−/−/A_2BR^−/− tumor-reactive T cells confirmed that immunosuppression in the tumor microenvironment was mediated by A_2AR on CD8⁺ T cells. Treatment with A_2AR antagonist mimicked A_2AR gene deletion in adoptive T cell immunotherapy. This therapeutic benefit of targeting A_2AR was independent of the anatomical location of tumor growth. The enhanced antitumor reactivity also led to the eradication of established intracranial tumors, which was associated with mouse survival and the maintenance of long-lasting, tumor-specific immunological memory. The blockade of the A_2AR on adoptively transferred T cells by synthetic A_2AR antagonist led to higher levels of IFN-γ secretion by tumor-infiltrating CD8⁺ T cells. These data clarify the mechanism of hypoxia-driven immunosuppression in the tumor microenvironment by A_2AR on tumor-reactive CD8⁺ T cells and show that selective A_2AR antagonists can be effective in improving the outcomes of T cell–based immunotherapies. Demonstration of the T cell dose dependency of tumor rejection points to a major limitation of current cancer immunotherapies, in which the presence of sufficient numbers of tumor-reactive T cells in a patient is not known.

Purpose: Though there is broad agreement on the beneficial impact of diversity in management and leadership roles, much of the innovative capacity of an organization is realized at the unit level in working teams. Recent research points to cultural diversity having an especially significant impact on innovation team performance. The reports also highlight the need for the optimal team operating principles to derive maximum benefit. To prepare such innovation teams for success, it is valuable to understand the dynamics of team diversity at the project level and the underlying barriers and opportunities presented.Design/methodology/approach: This paper reviews the literature and case studies on cultural inputs to ideation and innovation, assessing team diversity through readily available instruments and the deployment of the science of team science (SciTS) principles in innovation teams.Findings: The key learnings include the importance of establishing communication standards, SciTS principles, team assessment of thinking styles and the utility of cultural awareness instruments.Practical implications: Diversity provides a creative advantage for innovation teams. However, team dynamics play an important role in maximizing these advantages, and cross-cultural competence of team members is required. Deployment of appropriate assessment tools and team methodologies enhances the likelihood of successful outcomes including in remote team settings.Originality/value: Literature from diverse functional areas is summarized including the science of team science, organizational management, diversity and inclusion methodologies and ethnocultural dynamics. It provides pointers for the optimal formation and operating principles with highly culturally diverse teams.

Recent advances in subcutaneous drug delivery and device design are transforming the biopharmaceutical sector and improving patient care.

The subcutaneous route offers myriad benefits for the administration of biotherapeutics in both acute and chronic diseases, including convenience, cost effectiveness and the potential for automation through closed-loop systems. Recent advances in parenteral administration devices and the use of additives which enhance drug dispersion have generated substantial additional interest in IV to SQ switching studies. Designing pre-clinical and clinical studies using SQ mediated delivery however requires deep understanding of complex inter-related physiologies and transport pathways governing the interstitial matrix, vascular system and lymphatic channels. This expert review will highlight key structural features which contribute to transport and biodistribution in the subcutaneous space and also assess the impact of drug formulations. Based on the rapidly growing interest in the SQ delivery route, a number of potential areas for future development are highlighted, which are likely to allow continued evolution and innovation in this important area.