800 research outputs found

    Explainable AI for ML jet taggers using expert variables and layerwise relevance propagation

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    A framework is presented to extract and understand decision-making information from a deep neural network (DNN) classifier of jet substructure tagging techniques. The general method studied is to provide expert variables that augment inputs ("eXpert AUGmented" variables, or XAUG variables), then apply layerwise relevance propagation (LRP) to networks both with and without XAUG variables. The XAUG variables are concatenated with the intermediate layers after network-specific operations (such as convolution or recurrence), and used in the final layers of the network. The results of comparing networks with and without the addition of XAUG variables show that XAUG variables can be used to interpret classifier behavior, increase discrimination ability when combined with low-level features, and in some cases capture the behavior of the classifier completely. The LRP technique can be used to find relevant information the network is using, and when combined with the XAUG variables, can be used to rank features, allowing one to find a reduced set of features that capture part of the network performance. In the studies presented, adding XAUG variables to low-level DNNs increased the efficiency of classifiers by as much as 30-40\%. In addition to performance improvements, an approach to quantify numerical uncertainties in the training of these DNNs is presented.Comment: 38 pages, 30 figure

    Paper 2 : a systematic review of narrative therapy treatment outcomes for eating disorders : bridging the divide between practice‑based evidence and evidence‑based practice

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    Background: Narrative therapy has been proposed to have practice-based evidence however little is known about its research evidence-base in the treatment of eating disorders. The aim of this study was to conduct a systematic review of the outcome literature of narrative therapy for eating disorders. Method: Treatment outcome data were extracted from 33 eligible included studies following systematic search of five data bases. The study is reported according to Preferred Reporting items for Systematic Reviews and Meta-Analyses guidelines. Results: Of the identified 33 studies, 3 reported positive outcomes using psychometric instruments, albeit some were outdated. Otherwise, reported outcomes were based on therapy transcript material and therapist reports. The most commonly reported treatment outcome was in relation to shifts in identity narratives and improved personal agency with a trend towards under-reporting shifts in ED symptoms. Some improvements were reported in interpersonal and occupational engagement, reduced ED symptoms, and improved quality of life, however, there was an absence of standardized measures to support these reports. Conclusions: This systematic review found limited support for narrative therapy in the treatment of eating disorders through practice-based evidence in clinician reports and transcripts of therapy sessions. Less is known about systematic treatment outcomes of narrative therapy. There is a need to fill this gap to understand the effectiveness of narrative therapy in the treatment of EDs through systematic (1) Deliveries of this intervention; and (2) Reporting of outcomes. In doing so, the research arm of narrative therapy evidence base will become more comprehensively known

    Conditional in vivo deletion of LYN kinase has little effect on a BRCA1 loss-of-function-associated mammary tumour model

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    LYN kinase is expressed in BRCA1 loss-of-function-dependent mouse mammary tumours, in the cells of origin of such tumours, and in human breast cancer. Suppressing LYN kinase activity in BRCA1-defective cell lines, as well as in in vitro cultures of Brca1-null mouse mammary tumours, is deleterious to their growth. Here, we have examined the interaction between LYN kinase and BRCA1 loss-of-function in an in vivo mouse mammary tumour model, using conditional knockout Brca1 and Lyn alleles. Comparison of Brca1 tumour cohorts showed little difference in mammary tumour formation between animals that were wild type, heterozygous or homozygous for the conditional Lyn allele, although this was confounded by factors including incomplete Lyn recombination in some tumours. RNAseq analysis demonstrated that tumours with high levels of Lyn gene expression had a slower doubling time, but this was not correlated with levels of LYN staining in tumour cells themselves. Rather, high Lyn expression and slower tumour growth were likely a result of Bcell infiltration. The multifaceted role of LYN means it is likely to present difficulties as a therapeutic target in breast cancer

    Defining Ecological Drought for the Twenty-First Century

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    THE RISING RISK OF DROUGHT. Droughts of the twenty-first century are characterized by hotter temperatures, longer duration, and greater spatial extent, and are increasingly exacerbated by human demands for water. This situation increases the vulnerability of ecosystems to drought, including a rise in drought-driven tree mortality globally (Allen et al. 2015) and anticipated ecosystem transformations from one state to another—for example, forest to a shrubland (Jiang et al. 2013). When a drought drives changes within ecosystems, there can be a ripple effect through human communities that depend on those ecosystems for critical goods and services (Millar and Stephenson 2015). For example, the “Millennium Drought” (2002–10) in Australia caused unanticipated losses to key services provided by hydrological ecosystems in the Murray–Darling basin—including air quality regulation, waste treatment, erosion prevention, and recreation. The costs of these losses exceeded AUD $800 million, as resources were spent to replace these services and adapt to new drought-impacted ecosystems (Banerjee et al. 2013). Despite the high costs to both nature and people, current drought research, management, and policy perspectives often fail to evaluate how drought affects ecosystems and the “natural capital” they provide to human communities. Integrating these human and natural dimensions of drought is an essential step toward addressing the rising risk of drought in the twenty-first century

    "The extreme penalty of the law": mercy and the death penalty as aspects of state power in colonial Nyasaland, c. 1903-47

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    Open access article.Capital punishment was the pinnacle of the colonial judicial system and its use of state violence, but has previously been neglected as a topic of historical research in Africa. This article is based on the case files and legal records of over 800 capital trials – predominantly for murder – dating between 1900 and 1947. It outlines the functioning of the legal system in Nyasaland and the tensions between “violence” and “humanitarianism” in the use and reform of the death penalty. Capital punishment was a political penalty as much as a judicial punishment, with both didactic and deterrent functions: it operated through mercy and the sparing of condemned lives as well as through executions. Mercy in Nyasaland was consistent with colonial political objectives and cultural values: it was decided not only on the facts of cases, but according to British conceptions of “justice”, “order”, “criminality”, and “African” behaviour. This article analyses the use of mercy in Nyasaland to provide a lens on the nature of colonial governance, and the tensions between African and colonial understandings of violence.Arts and Humanities Research Council (UK) and the Beit Fund, University of Oxfor

    Targeted Inactivation of p12Cdk2ap1, CDK2 Associating Protein 1, Leads to Early Embryonic Lethality

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    Targeted disruption of murine Cdk2ap1, an inhibitor of CDK2 function and hence G1/S transition, results in the embryonic lethality with a high penetration rate. Detailed timed pregnancy analysis of embryos showed that the lethality occurred between embryonic day 3.5 pc and 5.5 pc, a period of implantation and early development of implanted embryos. Two homozygous knockout mice that survived to term showed identical craniofacial defect, including a short snout and a round forehead. Examination of craniofacial morphology by measuring Snout Length (SL) vs. Face Width (FW) showed that the Cdk2ap1+/− mice were born with a reduced SL/FW ratio compared to the Cdk2ap1+/+ and the reduction was more pronounced in Cdk2ap1−/− mice. A transgenic rescue of the lethality was attempted by crossing Cdk2ap1+/− animals with K14-Cdk2ap1 transgenic mice. Resulting Cdk2ap1+/−:K14-Cdk2ap1 transgenic mice showed an improved incidence of full term animals (16.7% from 0.5%) on a Cdk2ap1−/− background. Transgenic expression of Cdk2ap1 in Cdk2ap1−/−:K14-Cdk2ap1 animals restored SL/FW ratio to the level of Cdk2ap1+/−:K14-Cdk2ap1 mice, but not to that of the Cdk2ap1+/+:K14-Cdk2ap1 mice. Teratoma formation analysis using mESCs showed an abrogated in vivo pluripotency of Cdk2ap1−/− mESCs towards a restricted mesoderm lineage specification. This study demonstrates that Cdk2ap1 plays an essential role in the early stage of embryogenesis and has a potential role during craniofacial morphogenesis

    Anemia prevalence in women of reproductive age in low- and middle-income countries between 2000 and 2018

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    Anemia is a globally widespread condition in women and is associated with reduced economic productivity and increased mortality worldwide. Here we map annual 2000–2018 geospatial estimates of anemia prevalence in women of reproductive age (15–49 years) across 82 low- and middle-income countries (LMICs), stratify anemia by severity and aggregate results to policy-relevant administrative and national levels. Additionally, we provide subnational disparity analyses to provide a comprehensive overview of anemia prevalence inequalities within these countries and predict progress toward the World Health Organization’s Global Nutrition Target (WHO GNT) to reduce anemia by half by 2030. Our results demonstrate widespread moderate improvements in overall anemia prevalence but identify only three LMICs with a high probability of achieving the WHO GNT by 2030 at a national scale, and no LMIC is expected to achieve the target in all their subnational administrative units. Our maps show where large within-country disparities occur, as well as areas likely to fall short of the WHO GNT, offering precision public health tools so that adequate resource allocation and subsequent interventions can be targeted to the most vulnerable populations

    Cognitive interviewing of the US National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

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    The National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is a library of question items that enables patient reporting of adverse events (AEs) in clinical trials. This study contributes content validity evidence of the PRO-CTCAE by incorporating cancer patient input of the relevance and comprehensiveness of the item library

    The Bactofilin Cytoskeleton Protein BacM of Myxococcus xanthus Forms an Extended β-Sheet Structure Likely Mediated by Hydrophobic Interactions

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    Bactofilins are novel cytoskeleton proteins that are widespread in Gram-negative bacteria. Myxococcus xanthus, an important predatory soil bacterium, possesses four bactofilins of which one, BacM (Mxan_7475) plays an important role in cell shape maintenance. Electron and fluorescence light microscopy, as well as studies using over-expressed, purified BacM, indicate that this protein polymerizes in vivo and in vitro into ~3 nm wide filaments that further associate into higher ordered fibers of about 10 nm. Here we use a multipronged approach combining secondary structure determination, molecular modeling, biochemistry, and genetics to identify and characterize critical molecular elements that enable BacM to polymerize. Our results indicate that the bactofilin-determining domain DUF583 folds into an extended β-sheet structure, and we hypothesize a left-handed β-helix with polymerization into 3 nm filaments primarily via patches of hydrophobic amino acid residues. These patches form the interface allowing head-to-tail polymerization during filament formation. Biochemical analyses of these processes show that folding and polymerization occur across a wide variety of conditions and even in the presence of chaotropic agents such as one molar urea. Together, these data suggest that bactofilins are comprised of a structure unique to cytoskeleton proteins, which enables robust polymerization
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