Puff, The Magic Dragon, and the Estate Planner

With the legalization of medical and recreational marijuana in almost half of the states, practitioners need to be aware of the interface between marijuana and estate planning. This Article provides a discussion of the major issues that arise in this context. After bringing readers current with the history of legalized marijuana, the Article focuses on how marijuana use may impact a user’s capacity to execute a will and other estate planning documents. The Article then examines other estate planning concerns such as will and trust provisions conditioning benefits on the non-use of “illegal drugs” and the impact of marijuana use on life insurance policies. The Article wraps up with a discussion of how an estate planner may deal with marijuana-based assets when planning an estate and how to value those assets after the owner has died

Early Evidence on the use of Foreign Cash following the Tax Cuts and Jobs Act of 2017

The Tax Cuts and Jobs Act of 2017 (TCJA) imposes a mandatory repatriation tax on multinational firms’ unremitted foreign earnings, reducing internal capital market frictions through a deemed repatriation of unremitted foreign earnings and eliminating future repatriation tax costs. This change to the U.S. corporate tax system gives multinational firms access to lower cost internal capital (i.e., foreign cash). This study provides evidence that multinational firms with greater levels of pre-TCJA foreign cash increased their post-TCJA repurchases but did not change their shareholder dividends or capital expenditures. We further document that the increase in repurchases is driven by those firms that had greater pre-TCJA repatriation tax costs and firms in weaker financial health. This outcome is consistent with internal capital market theory and suggests a decrease in internal capital market frictions allows companies access to trapped foreign cash. However, our results suggest firms used the repatriated foreign cash on shareholder payouts rather than capital investment. This conflicts with a stated goal of the TCJA to spur domestic economic growth directly and highlights an unintended consequence of the TCJA

The threats endangering Australia's at-risk fauna

Reducing the rate of species extinctions is one of the great challenges of our time. Understanding patterns in the distribution and frequency of both threatened species and the threatening processes affecting them improves our ability to mitigate threats and prioritize management actions. In this quantitative synthesis of processes threatening Australian at-risk fauna, we find that species are impacted by a median of six threats (range 1–19), though there is considerable variation in numbers of threats among major taxonomic groups. Invasive species, habitat loss, biological resource use, natural systems modification and climate change are the processes most commonly affecting Australian threatened species. We identified an uneven distribution of research knowledge among species, with half of the total number of species-specific peer-reviewed scientific publications associated with only 11 threatened species (2.7%). Furthermore, the number of threats associated with each species was correlated with the research effort for that species, and research effort was correlated with body mass. Hence, there appears to be a research bias towards larger-bodied species, and certain charismatic species, that could result in inferences biased towards these favored species. However, after accounting for these effects we found that for birds, amphibians, reptiles and marine mammals body mass is positively correlated with the number of threats associated with each species. Many threats also co-occur, indicating that threat syndromes may be common

Improving Supervisor Evaluations Through the Use of Self Determination Contracts

Supervisor perceptions of employee competence in areas of work, social, and personal demands of the job often determine success or failure for the supported employee. This study involved three workers with disabilities who participated in a supported employment program. After being successfully hired in a job of their choosing, problems arose that jeopardized the successful completion of the placement phase. The workers used individualized self-determination contracts to improve supervisor evaluations. Specifically, they completed daily self-determination contracts to plan their work outcomes, manage their tasks, evaluate their performance, and make adjustments for their next opportunity to work. Results indicated that all three workers used self-determination strategies to improve their performance and meet the expectations of their respective employers.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

A multidimensional evaluation framework for personal learning environments

Evaluating highly dynamic and heterogeneous Personal Learning Environments (PLEs) is extremely challenging. Components of PLEs are selected and configured by individual users based on their personal preferences, needs, and goals. Moreover, the systems usually evolve over time based on contextual opportunities and constraints. As such dynamic systems have no predefined configurations and user interfaces, traditional evaluation methods often fall short or are even inappropriate. Obviously, a host of factors influence the extent to which a PLE successfully supports a learner to achieve specific learning outcomes. We categorize such factors along four major dimensions: technological, organizational, psycho-pedagogical, and social. Each dimension is informed by relevant theoretical models (e.g., Information System Success Model, Community of Practice, self-regulated learning) and subsumes a set of metrics that can be assessed with a range of approaches. Among others, usability and user experience play an indispensable role in acceptance and diffusion of the innovative technologies exemplified by PLEs. Traditional quantitative and qualitative methods such as questionnaire and interview should be deployed alongside emergent ones such as learning analytics (e.g., context-aware metadata) and narrative-based methods. Crucial for maximal validity of the evaluation is the triangulation of empirical findings with multi-perspective (end-users, developers, and researchers), mixed-method (qualitative, quantitative) data sources. The framework utilizes a cyclic process to integrate findings across cases with a cross-case analysis in order to gain deeper insights into the intriguing questions of how and why PLEs work

Integrative Analysis of Low- and High-Resolution eQTL

The study of expression quantitative trait loci (eQTL) is a powerful way of detecting transcriptional regulators at a genomic scale and for elucidating how natural genetic variation impacts gene expression. Power and genetic resolution are heavily affected by the study population: whereas recombinant inbred (RI) strains yield greater statistical power with low genetic resolution, using diverse inbred or outbred strains improves genetic resolution at the cost of lower power. In order to overcome the limitations of both individual approaches, we combine data from RI strains with genetically more diverse strains and analyze hippocampus eQTL data obtained from mouse RI strains (BXD) and from a panel of diverse inbred strains (Mouse Diversity Panel, MDP). We perform a systematic analysis of the consistency of eQTL independently obtained from these two populations and demonstrate that a significant fraction of eQTL can be replicated. Based on existing knowledge from pathway databases we assess different approaches for using the high-resolution MDP data for fine mapping BXD eQTL. Finally, we apply this framework to an eQTL hotspot on chromosome 1 (Qrr1), which has been implicated in a range of neurological traits. Here we present the first systematic examination of the consistency between eQTL obtained independently from the BXD and MDP populations. Our analysis of fine-mapping approaches is based on ‘real life’ data as opposed to simulated data and it allows us to propose a strategy for using MDP data to fine map BXD eQTL. Application of this framework to Qrr1 reveals that this eQTL hotspot is not caused by just one (or few) ‘master regulators’, but actually by a set of polymorphic genes specific to the central nervous system

Losartan Slows Pancreatic Tumor Progression and Extends Survival of SPARC-Null Mice by Abrogating Aberrant TGFβ Activation

Pancreatic adenocarcinoma, a desmoplastic disease, is the fourth leading cause of cancer-related death in the Western world due, in large part, to locally invasive primary tumor growth and ensuing metastasis. SPARC is a matricellular protein that governs extracellular matrix (ECM) deposition and maturation during tissue remodeling, particularly, during wound healing and tumorigenesis. In the present study, we sought to determine the mechanism by which lack of host SPARC alters the tumor microenvironment and enhances invasion and metastasis of an orthotopic model of pancreatic cancer. We identified that levels of active TGFβ1 were increased significantly in tumors grown in SPARC-null mice. TGFβ1 contributes to many aspects of tumor development including metastasis, endothelial cell permeability, inflammation and fibrosis, all of which are altered in the absence of stromal-derived SPARC. Given these results, we performed a survival study to assess the contribution of increased TGFβ1 activity to tumor progression in SPARC-null mice using losartan, an angiotensin II type 1 receptor antagonist that diminishes TGFβ1 expression and activation in vivo. Tumors grown in SPARC-null mice progressed more quickly than those grown in wild-type littermates leading to a significant reduction in median survival. However, median survival of SPARC-null animals treated with losartan was extended to that of losartan-treated wild-type controls. In addition, losartan abrogated TGFβ induced gene expression, reduced local invasion and metastasis, decreased vascular permeability and altered the immune profile of tumors grown in SPARC-null mice. These data support the concept that aberrant TGFβ1-activation in the absence of host SPARC contributes significantly to tumor progression and suggests that SPARC, by controlling ECM deposition and maturation, can regulate TGFβ availability and activation

Anatomical Specializations for Nocturnality in a Critically Endangered Parrot, the Kakapo (Strigops habroptilus)

The shift from a diurnal to nocturnal lifestyle in vertebrates is generally associated with either enhanced visual sensitivity or a decreased reliance on vision. Within birds, most studies have focused on differences in the visual system across all birds with respect to nocturnality-diurnality. The critically endangered Kakapo (Strigops habroptilus), a parrot endemic to New Zealand, is an example of a species that has evolved a nocturnal lifestyle in an otherwise diurnal lineage, but nothing is known about its' visual system. Here, we provide a detailed morphological analysis of the orbits, brain, eye, and retina of the Kakapo and comparisons with other birds. Morphometric analyses revealed that the Kakapo's orbits are significantly more convergent than other parrots, suggesting an increased binocular overlap in the visual field. The Kakapo exhibits an eye shape that is consistent with other nocturnal birds, including owls and nightjars, but is also within the range of the diurnal parrots. With respect to the brain, the Kakapo has a significantly smaller optic nerve and tectofugal visual pathway. Specifically, the optic tectum, nucleus rotundus and entopallium were significantly reduced in relative size compared to other parrots. There was no apparent reduction to the thalamofugal visual pathway. Finally, the retinal morphology of the Kakapo is similar to that of both diurnal and nocturnal birds, suggesting a retina that is specialised for a crepuscular niche. Overall, this suggests that the Kakapo has enhanced light sensitivity, poor visual acuity and a larger binocular field than other parrots. We conclude that the Kakapo possesses a visual system unlike that of either strictly nocturnal or diurnal birds and therefore does not adhere to the traditional view of the evolution of nocturnality in birds

An organelle-specific protein landscape identifies novel diseases and molecular mechanisms

Contains fulltext : 158967.pdf (publisher's version ) (Open Access)Cellular organelles provide opportunities to relate biological mechanisms to disease. Here we use affinity proteomics, genetics and cell biology to interrogate cilia: poorly understood organelles, where defects cause genetic diseases. Two hundred and seventeen tagged human ciliary proteins create a final landscape of 1,319 proteins, 4,905 interactions and 52 complexes. Reverse tagging, repetition of purifications and statistical analyses, produce a high-resolution network that reveals organelle-specific interactions and complexes not apparent in larger studies, and links vesicle transport, the cytoskeleton, signalling and ubiquitination to ciliary signalling and proteostasis. We observe sub-complexes in exocyst and intraflagellar transport complexes, which we validate biochemically, and by probing structurally predicted, disruptive, genetic variants from ciliary disease patients. The landscape suggests other genetic diseases could be ciliary including 3M syndrome. We show that 3M genes are involved in ciliogenesis, and that patient fibroblasts lack cilia. Overall, this organelle-specific targeting strategy shows considerable promise for Systems Medicine