Staying and Returning Dynamics of Young Children's Attention

In this paper, we decompose sustained attending behavior into components of continuous attention maintenance and attentional transitions and study how each of these components develops in young children. Our results in two experiments suggest that changes in children's ability to return attention to a target locus after distraction (“Returning”) play a crucial role in the development of sustained attention between the ages of 3.5-6 years, perhaps to a greater extent than changes in the ability to continuously maintain attention on the target (“Staying”). We further distinguish Returning from the behavior of transitioning attention away from task (“Leaving”) and provide evidence that Leaving is more strongly influenced by bottom-up factors, while Returning is invariant to these same bottom-up factors, suggesting a potentially greater contribution of top-down factors in Returning. Overall, these results (a) suggest the importance of understanding the cognitive process of transitioning attention for understanding sustained attention and its development, (b) provide an empirical paradigm within which to study this process, and (c) begin to characterize basic features of this process, namely its development and its relative dependence on top-down and bottom-up influences on attention.

BH3 profiling identifies ruxolitinib as a promising partner for venetoclax to treat T-cell prolymphocytic leukemia

Conventional therapies for patients with T-cell prolymphocytic leukemia (T-PLL) such as cytotoxic chemotherapy and alemtuzumab have limited efficacy and considerable toxicity. Several novel agent classes have demonstrated preclinical activity in T-PLL, including inhibitors of the JAK/STAT and TCR pathways, as well as histone deacetylase (HDAC) inhibitors. Recently, the BCL-2 inhibitor venetoclax also showed some clinical activity in T-PLL. We sought to characterize functional apoptotic dependencies in T-PLL to identify novel combination therapy in this disease. Twenty-four primary T-PLL patient samples were studied using BH3 profiling, a functional assay to assess the propensity of a cell to undergo apoptosis ('priming') and the relative dependence of a cell on different anti-apoptotic proteins. Primary T-PLL cells had a relatively low level of priming for apoptosis, and predominantly depended on BCL-2 and MCL-1 for survival. Selective pharmacologic inhibition of BCL-2 or MCL-1 induced cell death in primary T-PLL cells. Targeting JAK/STAT pathway with the JAK1/2 inhibitor ruxolitinib or HDAC with belinostat both independently increased dependence on BCL-2 but not MCL-1, thereby sensitizing T-PLL cells to venetoclax. Based on these results, we treated two patients with refractory T-PLL with the combination of venetoclax and ruxolitinib. We observed a deep response in the JAK3-mutated T-PLL and a stabilization of the unmutated disease. Our functional, precision medicine-based approach identified inhibitors of HDAC and the JAK/STAT pathway as promising combination partners for venetoclax, warranting further exploration of such combinations clinically in T-PLL.

Knowledge-Based Regularization in Generative Modeling

Prior domain knowledge can greatly help to learn generative models. However, it is often too costly to hard-code prior knowledge as a specific model architecture, so we often have to use general-purpose models. In this paper, we propose a method to incorporate prior knowledge of feature relations into the learning of general-purpose generative models. To this end, we formulate a regularizer that makes the marginals of a generative model to follow prescribed relative dependence of features. It can be incorporated into off-the-shelf learning methods of many generative models, including variational autoencoders and generative adversarial networks, as its gradients can be computed using standard backpropagation techniques. We show the effectiveness of the proposed method with experiments on multiple types of datasets and generative models.

Two Accounts of International Tax Justice

The contemporary international tax regime has been increasingly criticized over the years from varied perspectives, particularly as to the unfairness it produces for developing countries. Some commentators argue it is unjust due to the lack of participation of developing countries in the policymaking process on an equal footing. Others suggest the international tax regime was designed by affluent countries to respond to self-interested goals. Some note that its current institutional design creates opportunities for tax competition and avoidance, which more seriously affect developing economies due to their relative dependence on corporate income tax and their greater vulnerability to capital mobility. Others specifically criticize how taxing rights, that is, the entitlement of countries to tax cross-border transactions, are currently allocated between home and host countries and how they disfavour capital-importing, developing countries.

The Many Fields of (German) International Law

In recent years, interest in comparative approaches in the study of international law has grown. This chapter contributes to this endeavor with a focus on the particularities of academic international law in Germany, but also with an interest in methodology and a broader argument for attention to a particular set of factors behind differences in the interpretation and application of international law. Using sociological insights, it focuses on the professional contexts in which the different interpreters are embedded—the social and professional ‘fields’ in which they operate—and suggests connections between the shape of those contexts and the methodological and substantive commitments with which these interpreters approach international law. In Germany, the relative dependence of international law on the broader field of public law stands out as a differentiating characteristic.

External Resources and Indiscriminate Violence

Within a single conflict, the scale of government violence against civilians can vary greatly—from mass atrocities in one village to eerie restraint in the next. This article argues that the scale of anticivilian violence depends on a combatant's relative dependence on local and external sources of support. External resources make combatants less dependent on the local population, yet create perverse incentives for how the population is to be treated. Efforts by the opposition to interdict the government's external resources can reverse this effect, making the government more dependent on the local population. The article tests this relationship with disaggregated archival data on German-occupied Belarus during World War II. It finds that Soviet partisan attacks against German personnel provoked reprisals against civilians but that attacks against railroads had the opposite effect. Where partisans focused on disrupting German supply lines rather than killing Germans, occupying forces conducted fewer reprisals, burned fewer houses, and killed fewer people.

From Dependence Towards Independence in the Development of the Individual

In this talk to an Atlanta Psychiatric Clinic, Winnicott maintains that the early Freudian account of growth in terms of oral, anal, phallic and genital phases is insufficient. He charts growth in terms of the phases of dependence in early infancy until gradual independence in adulthood is more or less achieved. He sees this movement from dependence to independence as never completed. It is both a personal journey and a societal one. Winnicott elaborates three phases of the journey: ‘absolute dependence’, ‘relative dependence’ and ‘towards independence’. He cites many case examples of these phases.