What is Interpretability?

Funder: Ernest Oppenheimer Memorial Trust (ZA)Funder: Williamson, Rausing and Lipton HPS Trust Fund (GB)Funder: Wellcome Trust; doi: https://doi.org/10.13039/100004440Funder: Cambridge Commonwealth, European and International Trust; doi: https://doi.org/10.13039/501100003343Funder: Cambridge Commonwealth Trust; doi: https://doi.org/10.13039/501100003342Funder: Social Sciences and Humanities Research Council of Canada; doi: https://doi.org/10.13039/501100000155We argue that artificial networks are explainable and offer a novel theory of interpretability. Two sets of conceptual questions are prominent in theoretical engagements with artificial neural networks, especially in the context of medical artificial intelligence: (1) Are networks explainable, and if so, what does it mean to explain the output of a network? And (2) what does it mean for a network to be interpretable? We argue that accounts of "explanation" tailored specifically to neural networks have ineffectively reinvented the wheel. In response to (1), we show how four familiar accounts of explanation apply to neural networks as they would to any scientific phenomenon. We diagnose the confusion about explaining neural networks within the machine learning literature as an equivocation on "explainability," "understandability" and "interpretability." To remedy this, we distinguish between these notions, and answer (2) by offering a theory and typology of interpretation in machine learning. Interpretation is something one does to an explanation with the aim of producing another, more understandable, explanation. As with explanation, there are various concepts and methods involved in interpretation: Total or Partial, Global or Local, and Approximative or Isomorphic. Our account of "interpretability" is consistent with uses in the machine learning literature, in keeping with the philosophy of explanation and understanding, and pays special attention to medical artificial intelligence systems

Transcranial sonothrombolysis using high-intensity focused ultrasound: impact of increasing output power on clot fragmentation

Abstract Background The primary goal of this study was to investigate the relationship between increasing output power levels and clot fragmentation during high-intensity focused ultrasound (HIFU)-induced thrombolysis. Methods A HIFU headsystem, designed for brain applications in humans, was used for this project. A human calvarium was mounted inside the water-filled hemispheric transducer. Artificial thrombi were placed inside the skull and located at the natural focus point of the transducer. Clots were exposed to a range of acoustic output power levels from 0 to 400 W. The other HIFU operating parameters remained constant. To assess clot fragmentation, three filters of different mesh pore sizes were used. To assess sonothrombolysis efficacy, the clot weight loss was measured. Results No evidence of increasing clot fragmentation was found with increasing acoustic intensities in the majority of the study groups of less than 400 W. Increasing clot lysis could be observed with increasing acoustic output powers. Conclusion Transcranial sonothrombolysis could be achieved in vitro within seconds in the absence of tPA and without producing relevant clot fragmentation, using acoustic output powers of \u3c400 W

Total serum cholinesterase activity predicts hemodynamic changes during exercise and associates with cardiac troponin detection in a sex-dependent manner.

BACKGROUND: Imbalanced autonomic nervous system (ANS) activity is associated with poor cardiovascular outcome. However, clinically validated biomarkers to assess parasympathetic function are not yet available. We sought to evaluate parasympathetic dysfunction by measuring serum cholinesterase activity and to determine its relationship to high sensitive cardiac troponin T (hs-cTnT) as well as traditional non-invasive parameters of ANS function during exercise in apparently healthy individuals. METHODS: We enrolled 1526 individuals (mean age 49 ± 11 yr., 75% men) from the Tel Aviv Medical Center Inflammation Survey (TAMCIS). We used the acetylcholine (ACh) analog acetylthiocholine (ATCh) as a substrate that is hydrolyzed by both ACh degrading enzymes and reflects the total serum capacity for acetylcholine hydrolysis, referred to as cholinergic status (CS). All subjects performed a cardiac stress test reviewed on the spot by a cardiologist and multiple physiological and metabolic parameters including hs-cTnT were measured. RESULTS: CS values at rest predicted multiple exercise-hemodynamic changes. Heart rate recovery after exercise was inversely correlated to CS values (p  5 ng/L) presented with elevated CS levels compared to women with undetectable levels; 1423 ± 272.5 vs 1347 ± 297.9 (p = 0.02). An opposite trend was observed in men. Metabolic dysfunction parameters were also associated with CS elevation in both men and women. CONCLUSIONS: Parasympathetic dysfunction assessed by total serum cholinesterase activity predicts hemodynamic changes during exercise. CS is also associated with hs-cTnT detection in women and inversely so in men. Future studies to assess the potential clinical use of this new sex-specific biomarker in cardiovascular disease risk stratification are warranted

What Risk of Death Would People Take to be Cured of HIV, and Why? A Survey of People Living With HIV

People living with HIV (PLWHIV) can reasonably expect near-normal longevity, yet many express a willingness to assume significant risks to be cured. We surveyed 200 PLWHIV who were stable on antiretroviral therapy (ART) to quantify associations between the benefits they anticipate from a cure and their risk tolerance for curative treatments. Sixty-five per cent expected their health to improve if cured of HIV, 41% predicted the virus would stop responding to medications over the next 20 years and 54% predicted experiencing serious medication side effects in the next 20 years. Respondents’ willingness to risk death for a cure varied widely (median 10%, 75th percentile 50%). In multivariate analyses, willingness to risk death was associated with expected long-term side effects of ART, greater financial resources and being employed (all P < 0.05) but was not associated with perceptions of how their health would improve if cured

What Risk of Death Would People Take to be Cured of HIV, and Why? A Survey of People Living With HIV

People living with HIV (PLWHIV) can reasonably expect near-normal longevity, yet many express a willingness to assume significant risks to be cured. We surveyed 200 PLWHIV who were stable on antiretroviral therapy (ART) to quantify associations between the benefits they anticipate from a cure and their risk tolerance for curative treatments. Sixty-five per cent expected their health to improve if cured of HIV, 41% predicted the virus would stop responding to medications over the next 20 years and 54% predicted experiencing serious medication side effects in the next 20 years. Respondents’ willingness to risk death for a cure varied widely (median 10%, 75th percentile 50%). In multivariate analyses, willingness to risk death was associated with expected long-term side effects of ART, greater financial resources and being employed (all P < 0.05) but was not associated with perceptions of how their health would improve if cured

Block-Based Discrete Wavelet Transform-Singular Value Decomposition Image Watermarking Scheme Using Human Visual System Characteristics

Digital watermarking has been suggested as a way to achieve digital protection. The aim of digital watermarking is to insert the secret data into the image without significantly affecting the visual quality. This study presents a robust block-based image watermarking scheme based on the singular value decomposition (SVD) and human visual system in the discrete wavelet transform (DWT) domain. The proposed method is considered to be a block-based scheme that utilises the entropy and edge entropy as HVS characteristics for the selection of significant blocks to embed the watermark, which is a binary watermark logo. The blocks of the lowest entropy values and edge entropy values are selected as the best regions to insert the watermark. After the first level of DWT decomposition, the SVD is performed on the low-low sub-band to modify several elements in its U matrix according to predefined conditions. The experimental results of the proposed scheme showed high imperceptibility and high robustness against all image processing attacks and several geometrical attacks using examples of standard and real images. Furthermore, the proposed scheme outperformed several previous schemes in terms of imperceptibility and robustness. The security issue is improved by encrypting a portion of the important information using Advanced Standard Encryption a key size of 192-bits (AES-192)

Cash transfers for sustainable rural livelihoods? Examining the long-term productive effects of the Child Support Grant in South Africa

Cash transfers have received increased scholarly and policy attention, as a means of reducing poverty in the global South. While cash transfers are primarily intended to prevent impoverishment and deprivation, several studies suggest they can have 'productive' impacts, contributing to building sustainable livelihoods. However, pilot projects of unconditional cash transfers have often been too brief or too recent to determine how small, but regular, transfers can improve rural livelihoods over time. This paper explores potential long-term productive effects of cash transfers on rural household's livelihoods. This is done through revisiting, after 14 years, all (273) households in two South African villages included in an extensive livelihood and asset survey in 2002. That survey predated the phasing in of the Child Support Grant (CSG), targeted at impoverished children. When re-surveyed in 2016, some households had cumulatively received significant, while others little or no CSG income. Multivariate regression analysis shows how households that received more CGS income were more likely to invest in productive assets (e.g. small ploughs), and engage in poultry, staple crop and vegetable production

The endogenous retrovirus ENS-1 provides active binding sites for transcription factors in embryonic stem cells that specify extra embryonic tissue

<p>Abstract</p> <p>Background</p> <p>Long terminal repeats (LTR) from endogenous retroviruses (ERV) are source of binding sites for transcription factors which affect the host regulatory networks in different cell types, including pluripotent cells. The embryonic epiblast is made of pluripotent cells that are subjected to opposite transcriptional regulatory networks to give rise to distinct embryonic and extraembryonic lineages. To assess the transcriptional contribution of ERV to early developmental processes, we have characterized <it>in vitro </it>and <it>in vivo </it>the regulation of ENS-1, a host adopted and developmentally regulated ERV that is expressed in chick embryonic stem cells.</p> <p>Results</p> <p>We show that <it>Ens-1 </it>LTR activity is controlled by two transcriptional pathways that drive pluripotent cells to alternative developmental fates. Indeed, both Nanog that maintains pluripotency and Gata4 that induces differentiation toward extraembryonic endoderm independently activate the LTR. Ets coactivators are required to support Gata factors' activity thus preventing inappropriate activation before epigenetic silencing occurs during differentiation. Consistent with their expression patterns during chick embryonic development, Gata4, Nanog and Ets1 are recruited on the LTR in embryonic stem cells; in the epiblast the complementary expression of Nanog and Gata/Ets correlates with the <it>Ens-1 </it>gene expression pattern; and Ens-1 transcripts are also detected in the hypoblast, an extraembryonic tissue expressing Gata4 and Ets2, but not Nanog. Accordingly, over expression of Gata4 in embryos induces an ectopic expression of <it>Ens-1</it>.</p> <p>Conclusion</p> <p>Our results show that <it>Ens-1 </it>LTR have co-opted conditions required for the emergence of extraembryonic tissues from pluripotent epiblasts cells. By providing pluripotent cells with intact binding sites for Gata, Nanog, or both, <it>Ens-1 </it>LTR may promote distinct transcriptional networks in embryonic stem cells subpopulations and prime the separation between embryonic and extraembryonic fates.</p

The human body at cellular resolution: the NIH Human Biomolecular Atlas Program

Abstract: Transformative technologies are enabling the construction of three-dimensional maps of tissues with unprecedented spatial and molecular resolution. Over the next seven years, the NIH Common Fund Human Biomolecular Atlas Program (HuBMAP) intends to develop a widely accessible framework for comprehensively mapping the human body at single-cell resolution by supporting technology development, data acquisition, and detailed spatial mapping. HuBMAP will integrate its efforts with other funding agencies, programs, consortia, and the biomedical research community at large towards the shared vision of a comprehensive, accessible three-dimensional molecular and cellular atlas of the human body, in health and under various disease conditions