Cornucopia Reloaded: Load Barriers for CHERI Heap Temporal Safety

Violations of temporal memory safety (“use after free”, “UAF”) continue to pose a significant threat to software security. The CHERI capability architecture has shown promise as a technology for C and C++ language reference integrity and spatial memory safety. Building atop CHERI, prior works – CHERIvoke and Cornucopia – have explored adding heap temporal safety. The most pressing limitation of Cornucopia was its impractical “stop-the-world” pause times. We present Cornucopia Reloaded, a re-designed drop-in replacement implementation of CHERI temporal safety, using a novel architectural feature – a per-page capability load barrier, added in Arm’s Morello prototype CPU and CHERI- RISC-V – to nearly eliminate application pauses. We analyze the performance of Reloaded as well as Cornucopia and CHERIvoke on Morello, using the CHERI-compatible SPEC CPU2006 INT workloads to assess its impact on batch workloads and using pgbench and gRPC QPS as surrogate interactive workloads. Under Reloaded, applications no longer experience significant revocation-induced stop-the-world periods, without additional wall- or CPU-time cost over Cornucopia and with median 87% of Cornucopia’s DRAM traffic overheads across SPEC CPU2006 and < 50% for pgbench.Defense Advanced Research Projects Agency (DARPA) under Contract No. HR0011-18-C-0016 (“ECATS”) and Contract No. HR0011-23-C-0031 ("MTSS"

Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications.

Acknowledgements: This work was supported by funding from the European and American Thyroid Associations, the Erasmus University Rotterdam, the Dutch Organization for Scientific Research (NWO) (M.Med.), and the NIH (grants R35GM118335 and T32DK110966). Acknowledgments and study-specific acknowledgments are provided in the Supplementary Note. We conducted this research using the UK Biobank resource under the application numbers 53723 and 20272.Funder: This work was supported by funding from the European and American Thyroid Associations, the Erasmus University Rotterdam, and the Dutch Organization for Scientific Research (NWO).To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases

Weighted Burgers Vector analysis of orientation fields from high-angular resolution electron backscatter diffraction.

The Weighted Burgers Vector (WBV) method can extract information about dislocation types and densities present in distorted crystalline materials from electron backscatter diffraction (EBSD) maps, using no assumptions about which slip systems might be present. Furthermore, high-angular resolution EBSD (HR-EBSD) uses a cross-correlation procedure to increase the angular precision of EBSD measurements by an order of magnitude compared to conventional EBSD. However, the WBV technique has not previously been applied to HR-EBSD data and therefore it remains unclear as to which low-angle substructures can be reliably characterised by WBV analysis of conventional EBSD data and which require additional HR-EBSD processing. To establish some practical examples that can be used to guide future data-acquisition strategies, we compare the output of the WBV method when applied to conventional EBSD data and HR-EBSD data collected from the most common minerals in Earth's lower crust (plagioclase feldspar) and upper mantle (olivine). The results demonstrate that HR-EBSD and WBV processing are complementary techniques. The increase in angular precision achieved with HR-EBSD processing allows low-angle (on the order of 0.1°) structures, which are obscured by noise in conventional EBSD data, to be analyzed quantitatively using the WBV method. Combining the WBV and HR-EBSD methods increases the precision of calculated WBV directions, which is essential when using information about active slip systems to infer likely deformation mechanisms from naturally deformed microstructures. This increase in precision is particularly important for low-symmetry crystals, such as plagioclase, that have a wide range of available slip systems that vary in relative activity with changing pressure, temperature and differential stress. Because WBV directions are calculated using no assumptions about which slip systems may be present, combining this technique with HR-EBSD to refine the precision of lattice orientation gradients is ideal for investigating complex natural materials with unknown deformation histories

Patient experiences of Cytosponge: a qualitative study

Peer reviewed: TrueObjective: Cytosponge is a novel technology for oesophageal pathology diagnosis. Uses include diagnosis of Barrett’s oesophagus and as a triage tool to prioritise upper gastrointestinal endoscopy. Patient experience is a key component of quality care. Previous work has developed endoscopy patient-reported experience measures. An appropriate tool to measure patient experience of Cytosponge is required. The aim of this work was to describe the patient experience of Cytosponge. Design/Method: Individuals aged 18 years or over, who had undergone Cytosponge from September 2020 to March 2021, were invited to participate in a semi-structured interview. Interviews were audio-recorded, transcribed verbatim and anonymised. Thematic analysis was undertaken. Themes were organised into two overarching areas relating to patient experiences and patient perceptions of the test. Results: 19 patients underwent interview (aged 37–80 years, 13 male). In terms of patient experiences of Cytosponge, five themes were identified: emotional reaction; expectations; environment and physical process; sensory experience; communication and information. All themes were present across all procedural phases, aside from sensory experience which was only present during the test. With regard to perception of the test, two major themes were identified: test novelty (encompassing patient awareness of the test and reaction to the new test) and trusting the test results. Conclusion: Patients must remain central to novel technologies such as Cytosponge. Measuring patient experience is essential to achieve that. This study demonstrates five major themes which describe the patient experience of this procedure. These have been used to adapt the Newcastle ENDOPREM for use in Cytosponge

Generalized Partitioned Local Depth

Acknowledgements: The authors thank Katherine Moore, Richard Darling, several individuals at Metron, Inc., and others for stimulating discussions on communities in data.AbstractIn this paper, we provide a generalization of the concept of cohesion as introduced recently by Berenhaut et al. (Proc Natl Acad Sci 119:2003634119, 2022). The formulation presented builds on the technique of partitioned local depth by distilling two key probabilistic concepts: local relevance and support division. Earlier results are extended within the new context, and examples of applications to revealing communities in data with uncertainty are included. The work sheds light on the foundations of partitioned local depth, and extends the original ideas to enable probabilistic consideration of uncertain, variable and potentially conflicting information.</jats:p

Flat-sky angular power spectra revisited

Abstract We revisit the flat-sky approximation for evaluating the angular power spectra of projected random fields by retaining information about the correlations along the line of sight. For the case of projections with broad, overlapping radial window functions, these line-of-sight correlations are suppressed and are ignored in the commonly adopted Limber approximation. However, retaining the correlations is important for narrow window functions or unequal-time spectra but introduces significant computational difficulties due to the highly oscillatory nature of the integrands involved. We deal with the integral over line-of-sight wave-modes in the flat-sky approximation analytically, using the FFTlog expansion of the 3D power spectrum. This results in an efficient computational method, which is a substantial improvement compared to any full-sky approaches. We apply our results to galaxy clustering (with and without redshift-space distortions), CMB lensing and galaxy lensing observables in a flat ΛCDM universe. In the case of galaxy clustering, we find excellent agreement with the full-sky results on large (percent-level agreement) and intermediate or small (subpercent agreement) scales, dramatically out-performing the Limber approximation for both wide and narrow window functions, and in equal- and unequal-time cases. In the cases of lensing, we show on the full-sky that the angular power spectrum of the lensing convergence can be very well approximated by projecting the 3D Laplacian (rather than the correct angular Laplacian) of the gravitational potential, even on large scales. Combining this approximation with our flat-sky techniques provides an efficient and accurate evaluation of the CMB lensing angular power spectrum on all scales. We further analyse the clustering and lensing angular power spectra by isolating the projection effects due to the observable- and survey-specific window functions, separating them from the effects due to integration along the line of sight and unequal-time mixing in the 3D power spectrum. All of the angular power spectrum results presented in this paper are obtained using a Python code implementation, which we make publicly available.</jats:p

Vitamin D is associated with reduced risk of Sjögren's syndrome: a Mendelian randomization study.

Sjögren’s syndrome is an autoimmune disease characterised by lymphocytic infiltration of exocrine glands, but also systemic features such as arthritis, vasculitis, pulmonary and neurological dysfunction. Despite its impact on quality of life and physical function, no disease-modifying drugs have been approved. Some observational studies have linked vitamin D deficiency to increased Sjögren’s risk [1], but these findings are susceptible to confounding and reverse causation. Clinical trial evidence suggests that vitamin D supplementation reduces overall autoimmune disease risk [2], but whether this applies to Sjögren’s is not known. Mendelian randomization (MR) uses genetic variants as instrumental variables to estimate the effect of an exposure on an outcome that is typically more robust to these biases. Prior MR studies found no evidence for a link between vitamin D and Sjögren’s, but were limited by poor case definition and/or statistical power [3,4]. The aim of this MR study was to estimate the effect of genetically predicted vitamin D level on risk of primary Sjögren’s syndrome

Engineers on responsibility: feminist approaches to who’s responsible for ethical AI

Acknowledgements: Many thanks to Dr Stephen Cave, Director of the Institute of Technology and Humanity, and Dr Youngcho Lee, our research assistant on the Gender and Technology project. Many thanks also to the editorial team and reviewers at Ethics and Information Technology for their kind and thoughtful feedback. Finally, we would like to thank our interviewees for their generosity and their time.AbstractResponsibility has become a central concept in AI ethics; however, little research has been conducted into practitioners’ personal understandings of responsibility in the context of AI, including how responsibility should be defined and who is responsible when something goes wrong. In this article, we present findings from a 2020–2021 data set of interviews with AI practitioners and tech workers at a single multinational technology company and interpret them through the lens of feminist political thought. We reimagine responsibility in the context of AI development and deployment as the product of work cultures that enable tech workers to be responsive and answerable for their products over the long and short term. From our interviews, we identify three key pain points in understanding the distribution of responsibility between actors and developing responsible design and deployment practices: (1) unstable business ecosystems and AI lifecycles, which require an approach to responsibility that accounts for the dynamic nature of these systems; (2) the issue of incentivizing engineers to take responsibility for the mundane maintenance practices essential to the functioning of AI systems and (3) the need to overcome individual and structural barriers to taking ownership over AI products and their effects. From these findings, we make three recommendations based on feminist theory: (1) organisations should move from a static model of responsibility to a dynamic and ethically motivated response-ability; (2) companies need to revalue care and maintenance practices; and (3) firms must move away from individualistic ideas of responsibility towards fostering wider cultures of responsibility.</jats:p

Surface codes, quantum circuits, and entanglement phases

Surface codes–leading candidates for quantum error correction (QEC)–and entanglement phases–a key notion for many-body quantum dynamics–have heretofore been unrelated. Here, we establish a link between the two. We map two-dimensional (2D) surface codes under a class of incoherent or coherent errors (bit flips or uniaxial rotations) to $(1+1)$D free-fermion quantum circuits via Ising models. We show that the error-correcting phase implies a topologically nontrivial area law for the circuit's 1D long-time state $\ket{\Psi_\infty}$. Above the error threshold, we find a topologically trivial area law for incoherent errors and logarithmic entanglement in the coherent case. In establishing our results, we formulate 1D parent Hamiltonians for $\ket{\Psi_\infty}$ via linking Ising models and 2D scattering networks, the latter displaying respective insulating and metallic phases and setting the 1D fermion gap and topology via their localization length and topological invariant. We expect our results to generalize to a duality between the error-correcting phase of ($d+1$)D topological codes and $d$-dimensional area laws; this can facilitate assessing code performance under various errors. The approach of combining Ising models, scattering networks, and parent Hamiltonians can be generalized to other fermionic circuits and may be of independent interest.This work was supported by EPSRC grant EP/V062654/1, a Leverhulme Early Career Fellowship, the Newton Trust of the University of Cambridge, and in part by the ERC Starting Grant No. 678795 TopInSy. Our simulations used resources at the Cambridge Service for Data Driven Discovery operated by the University of Cambridge Research Computing Service (www.csd3.cam.ac.uk), provided by Dell EMC and Intel using EPSRC Tier-2 funding via grant EP/T022159/1, and STFC DiRAC funding (www.dirac.ac.uk)

Glioblastoma may evade immune surveillance through primary cilia-dependent signaling in an IL-6 dependent manner

Peer reviewed: TrueAcknowledgements: The authors express gratitude to Michelle Moore and Lisa Martin for their tireless administrative support of the Neurosurgical Oncology Unit.Glioblastoma is the most common, malignant primary brain tumor in adults and remains universally fatal. While immunotherapy has vastly improved the treatment of several solid cancers, efficacy in glioblastoma is limited. These challenges are due in part to the propensity of glioblastoma to recruit tumor-suppressive immune cells, which act in conjunction with tumor cells to create a pro-tumor immune microenvironment through secretion of several soluble factors. Glioblastoma-derived EVs induce myeloid-derived suppressor cells (MDSCs) and non-classical monocytes (NCMs) from myeloid precursors leading to systemic and local immunosuppression. This process is mediated by IL-6 which contributes to the recruitment of tumor-associated macrophages of the M2 immunosuppressive subtype, which in turn, upregulates anti-inflammatory cytokines including IL-10 and TGF-β. Primary cilia are highly conserved organelles involved in signal transduction and play critical roles in glioblastoma proliferation, invasion, angiogenesis, and chemoradiation resistance. In this perspectives article, we provide preliminary evidence that primary cilia regulate intracellular release of IL-6. This ties primary cilia mechanistically to tumor-mediated immunosuppression in glioblastomas and potentially, in additional neoplasms which have a shared mechanism for cancer-mediated immunosuppression. We propose potentially testable hypotheses of the cellular mechanisms behind this finding