We present Intercloud, a decentralised economic network in which streams of private data are secured by Watcher swarms that observe only cryptographic hashes, never plaintext. Intercloud requires no global consensus beyond a single shared random seed per epoch. Two mechanisms provide security: (i) ripple deduplication via epoch-stamped identifiers, preventing any ripple from propagating through the same node twice per epoch, guaranteeing termination without global coordination; and (ii) chilling-effect consensus, in which a swarm reaches finality by attesting to the absence of conflicting evidence rather than voting between alternatives. Any conflicting attestation automatically yields a self-certifying Proof of Corruption. We prove four main results. First, execution ripples terminate in bounded time via the ripple-ID mechanism. Second, a swarm of about 35 Watchers – assigned by a verifiable random function, independent of total network size – suffices for double-spending prevention, matching Hoepman's lower bound. Third, two correct clients can hold conflicting finality attestations only if the adversary compromises a supermajority of the assigned swarm or eclipses both clients from all honest nodes; we prove necessity and sufficiency. Fourth, Buridan's Principle does not apply: the consensus question is absence of evidence, not a binary choice on a continuous input. We also develop a complete economic model. Local coins are issued and retired by currency streams; security weight tracks value automatically as Intercoin weight adjusts at each epoch shuffle. Junior nodes detect corruption and earn lottery rewards for propagating Proofs of Corruption; vesting makes corruption economically irrational. The coin and content layers are strictly separated: regulators observe weight flows without learning amounts, coin types, identities, or rules.
As extreme heat events in New York City increase in frequency and intensity, existing response strategies must evolve to address growing risks to public health and infrastructure. This paper examines updates to the City’s (hereafter, ‘the City’ refers to the municipal government) heat emergency approach, based on initiatives piloted during the 2024 and 2025 summer seasons. The study outlines key changes to public messaging, operational planning, and community engagement. Messaging was revised to emphasise the health risks of extreme heat and promote earlier individual preparedness. The City expanded its approach beyond traditional Cooling Centers, introducing a broader concept of ‘Cool Options’ that includes a wider range of indoor and outdoor locations accessible to residents. New mapping tools were developed to provide continuous public access to information on cooling options across the city. The paper also describes targeted strategies to reach vulnerable populations, including partnerships with community organisations and the distribution of heat safety resources. Additional initiatives focused on improving accessibility, increasing awareness, and supporting at-risk groups during prolonged heat events. The findings demonstrate the importance of flexible, community-focused approaches to managing extreme heat. Continued evaluation and expansion of these strategies are expected to strengthen resilience and reduce heat-related health impacts in future increasingly severe conditions. This article is also included in The Business & Management Collection which can be accessed at https://hstalks.com/business/.
The 2022 global outbreak of clade IIb mpox represented a turning point in public health’s handling of poxviruses. The primary vaccine available for the prevention of mpox is modified vaccinia Ankara from Bavarian-Nordic (MVA-BN). We previously reported a nondurable and low-avidity antibody response against mpox elicited by MVA-BN. In this study, we expanded upon this knowledge by employing a microneutralization assay to measure monkeypox virus (MPXV) neutralizing titers and a multiplexed immunoassay to assess IgG titers and avidity against eight MPXV antigens and two vaccinia antigens. Through a machine learning analysis, we uncovered that MVA-BN vaccinees without prior smallpox vaccination largely return to a baseline seroprofile within a year of immunization. Notably, we identified a discrete population within this group that mounted a robust neutralizing antibody response associated with a longer dosing interval during the MVA-BN primary series. Furthermore, we found that boosting with a third dose of MVA-BN increases IgG avidity against certain MPXV antigens, as part of a booster-specific seroprofile. These findings provide critical insights into optimizing immune responses through MVA-BN boosters, presenting a potential approach to addressing the limited MPXV-specific immunity observed following the primary series.
Introduction and Objective: In NOD mice, impaired T cell development and negative selection are implicated in disease development. However, in T1D patients, it remains unknown whether abnormalities in thymic selection contribute to disease development. Our knowledge of human T Cell Receptor (TCR) repertoire formation is limited by lack of access to human thymi. Thus, humanized mice provide a unique opportunity to investigate formation of the human TCR repertoire. Methods: We utilized the Personalized Immune (PI) Mouse model, in which partially HLA-matched fetal thymic tissue and adult T1D or Healthy Control (HC) bone marrow CD34+ Hematopoietic Stem Cells are engrafted in immunodeficient mice. Following human T cell reconstitution, whole thymocytes are used for scRNA/TCR sequencing and DNA isolated from FACS-sorted thymocytes is used for high throughput TCRbeta CDR3 sequencing. Results: Published studies show that hydrophobicity of the TCR midCDR3 (mCDR3) region correlates with autoreactivity. In HC-derived mice, mCDR3 hydrophobicity increased during positive selection and then decreased in mature CD4 single positive (SP) cells compared to CD69+ CD4/8 double positive thymocytes, indicating effective selection processes. In T1D-derived mice, hydrophobicity increased during positive selection, albeit to a lesser extent at certain lengths of the mCDR3 region and failed to decrease as the cells matured into CD4SP cells, indicating defective negative selection. Using scRNA sequencing, Clusters 2 and 10 were significantly enriched in HC mice and correspondingly depleted in T1D mice. Using Chopp et al., 2020 as a reference, these two clusters were associated with hsDP3 and Sig4 maturation stages which precede positive selection and demonstrate features related to negatively selected subsets respectively. Conclusion: We provide in-vivo evidence both at the physio-chemical and transcriptional level, for abnormalities in thymocyte selection in human T1D-derived human immune systems. Disclosure V. Agashe: None. B. Vermette: None. R. Winchester: None. M. Sykes: None. Funding 4R01AI1778721UG3DK142184U01DK123559
Contrast‑associated acute kidney injury (CA-AKI) is a common and serious complication of coronary angiography. Supplemental oxygen therapy has been proposed as a simple strategy to reduce CA-AKI by improving renal oxygenation, but existing trial results are inconsistent. This systematic review and meta-analysis evaluated the efficacy of oxygen therapy in preventing CA-AKI among patients undergoing coronary angiography. We conducted a systematic review and meta-analysis in accordance with PRISMA guidelines, searching PubMed, Google Scholar, Scopus, Web of Science, and Embase from inception to December 2025. Studies evaluating post-angiography serum creatinine levels and the incidence of CA-AKI were included. Data were analyzed using random-effects models to account for between-study variability. Continuous outcomes were pooled as mean differences (SMDs) using the generic inverse variance method, while dichotomous outcomes were summarized as risk ratios (RRs). Heterogeneity among studies was assessed using the I² statistic, We screened 9,676 potential articles, and included five randomized controlled trials. Oxygenation therapy was associated with a significant reduction in serum creatinine levels at 48 h post-procedure, with a mean difference of − 0.10 mg/dL (95
