The role of human cytochrome P450 2E1 in liver inflammation and fibrosis.

Cytochrome P450 2E1 (CYP2E1) plays an important role in alcohol and toxin metabolism by catalyzing the conversion of substrates into more polar metabolites and producing reactive oxygen species. Reactive oxygen species-induced oxidative stress promotes hepatocyte injury and death, which in turn induces inflammation, activation of hepatic stellate cells, and liver fibrosis. Here, we analyzed mice expressing only the human CYP2E1 gene (hCYP2E1) to determine differences in hCYP2E1 versus endogenous mouse Cyp2e1 function with different liver injuries. After intragastric alcohol feeding, CYP2E1 expression was induced in both hCYP2E1 and wild-type (Wt) mice. hCYP2E1 mice had greater inflammation, fibrosis, and lipid peroxidation but less hepatic steatosis. In addition, hCYP2E1 mice demonstrated increased expression of fibrogenic and proinflammatory genes but decreased expression of de novo lipogenic genes compared to Wt mice. Lipidomics of free fatty acid, triacylglycerol, diacylglycerol, and cholesterol ester species and proinflammatory prostaglandins support these conclusions. Carbon tetrachloride-induced injury suppressed expression of both mouse and human CYP2E1, but again hCYP2E1 mice exhibited greater hepatic stellate cell activation and fibrosis than Wt controls with comparable expression of proinflammatory genes. By contrast, 14-day bile duct ligation induced comparable cholestatic injury and fibrosis in both genotypes. Conclusion: Alcohol-induced liver fibrosis but not hepatic steatosis is more severe in the hCYP2E1 mouse than in the Wt mouse, demonstrating the use of this model to provide insight into the pathogenesis of alcoholic liver disease. (Hepatology Communications 2017;1:1043-1057)

Learning where to learn: Gradient sparsity in meta and continual learning

Finding neural network weights that generalize well from small datasets is difficult. A promising approach is to learn a weight initialization such that a small number of weight changes results in low generalization error. We show that this form of meta-learning can be improved by letting the learning algorithm decide which weights to change, i.e., by learning where to learn. We find that patterned sparsity emerges from this process, with the pattern of sparsity varying on a problem-by-problem basis. This selective sparsity results in better generalization and less interference in a range of few-shot and continual learning problems. Moreover, we find that sparse learning also emerges in a more expressive model where learning rates are meta-learned. Our results shed light on an ongoing debate on whether meta-learning can discover adaptable features and suggest that learning by sparse gradient descent is a powerful inductive bias for meta-learning systems

Learning where to learn: Gradient sparsity in meta and continual learning

Finding neural network weights that generalize well from small datasets is difficult. A promising approach is to learn a weight initialization such that a small number of weight changes results in low generalization error. We show that this form of meta-learning can be improved by letting the learning algorithm decide which weights to change, i.e., by learning where to learn. We find that patterned sparsity emerges from this process, with the pattern of sparsity varying on a problem-by-problem basis. This selective sparsity results in better generalization and less interference in a range of few-shot and continual learning problems. Moreover, we find that sparse learning also emerges in a more expressive model where learning rates are meta-learned. Our results shed light on an ongoing debate on whether meta-learning can discover adaptable features and suggest that learning by sparse gradient descent is a powerful inductive bias for meta-learning systems

Economic challenges and success in the post-COVID era: A CAGE Policy Report

In 2008 there was an expectation of major reform to social and economic structures following the financial crisis. The European Union (EU) referendum of 2016, and the UK’s subsequent exit from the EU in 2020, was also signalled as a turning point that would bring about epochal change. Now, in the waning of the coronavirus pandemic, we are experiencing a similar rhetoric. There is widespread agreement that the pandemic will usher in big changes for the economy and society, with the potential for major policy reform. But what will be the long-term impacts of the pandemic on the UK economy? Is the right response a “new settlement” or is some alternative approach likely to be more beneficial? This report puts forward a new perspective on the pandemic-related changes that could be ahead. The central theme is assessing the viability of epochal reform in policymaking. There seems to be a relentless desire for making big changes; however, there is arguably not enough recognition of how current settings and history can hold back these efforts. Foreword by: Dame Frances Cairncross, CBE, FRSE

IDENTIFIKASI TAHAPAN SELF-SILENCING DALAM HUBUNGAN BERPACARAN EMERGING ADULTHOOD

Self-silencing adalah ketidakhadiran komunikasi efektif dalam hubungan sehingga individu tidak mengekspresikan pemikiran, perasaan serta keinginan yang sebenarnya kepada pasangan. Penelitian ini dilakukan dengan metode kualitatif dengan desain studi kasus.  Tujuan penelitian adalah memperkaya eksplorasi mengenai tahapan yang mencangkup penyebab, bentuk, dan dampak self-silencing dalam hubungan berpacaran emerging adulthood. Peneliti menggunakan teknik purposive sampling. Pengambilan data dilakukan dengan wawancara terhadap dua pasangan yang memiliki indikasi self-silencing berdasarkan open-ended questionnaire yang disusun. Data dari kedua pasangan melalui tahap triangulasi dan dianalisis dengan analisis tematik. Hasil penelitian menunjukkan bahwa terdapat perbedaan dalam penyebab, tahapan, dan dampak self-silencing bagi laki-laki dan perempuan. Temuan ini merupakan kebaruan dalam penelitian tentang self-silencing. Terdapat beberapa persamaan di faktor internal penyebab self-silencing, tetapi seluruh faktor eksternal dalam laki-laki dan perempuan memiliki perbedaan. Self-silencing perempuan cenderung berdampak terhadap relasi sedangkan laki-laki berdampak pada dirinya sendiri. Untuk tahapan, perempuan bisa keluar dari self-silencing akibat dorongan internal. Sementara pada laki-laki, walaupun memiliki motivasi internal, mereka cenderung butuh dorongan eksternal dari pasangan. Bentuk self-silencing antara laki-laki dan perempuan memiliki kemiripan, mereka sama-sama menunjukkan self-silencing dengan diam untuk menghindari konflik dan menunda komunikasi. Penelitian ini bermanfaat bagi emerging adult untuk meningkatkan kesadaran pentingnya berkomunikasi efektif dalam hubungan berpacaran. Keterbatasan penelitian ini adalah latar belakang budaya partisipan yang serupa sehingga informasi yang disampaikan menjadi terbatas pada konteks tertentu. Penelitian selanjutnya dapat mencari partisipan dengan latar belakang budaya yang lebih beragam untuk memperkaya informasi

Mental Health Response in Haiti in the Aftermath of the 2010 Earthquake: A Case Study for Building Long-Term Solutions

Significant challenges exist in providing safe, effective, and culturally sound mental health and psychosocial services when an unforeseen disaster strikes in a low-resource setting. We present here a case study describing the experience of a transnational team in expanding mental health and psychosocial services delivered by two health care organizations, one local (Zanmi Lasante) and one international (Partners in Health), acting collaboratively as part of the emergency response to the 2010 Haiti earthquake. In the year and a half following the earthquake, Zanmi Lasante and Partners in Health provided 20,000 documented individual and group appointments for mental health and psychosocial needs. During the delivery of disaster response services, the collaboration led to the development of a model to guide the expansion and scaling up of community-based mental health services in the Zanmi Lasante health care system over the long-term, with potential for broader scale-up in Haiti. This model identifies key skill packages and implementation rules for developing evidence-based pathways and algorithms for treating common mental disorders. Throughout the collaboration, efforts were made to coordinate planning with multiple organizations interested in supporting the development of mental health programs following the disaster, including national governmental bodies, nongovernmental organizations, universities, foreign academic medical centers, and corporations. The collaborative interventions are framed here in terms of four overarching categories of action: direct service delivery, research, training, and advocacy. This case study exemplifies the role of psychiatrists working in low-resource settings as public health program implementers and as members of multidisciplinary teams. (Harv Rev Psychiatry 2012;20:68–77.

Reconstructing Metaphorical Meaning

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