3,051 research outputs found

    Innovations and Trends in Pension Plan Coverage, Pension Type and Plan Design

    Get PDF
    In this paper, we outline recent trends in employer pension pIan structure in the United States, focusing on plan coverage, plan type and pension plan design. We then identify the key factors that we believe will shape company-sponsored pension design in the future, drawing conclusions from a review of recent research and practice. Finally, we offer a cautious prognosis about the future of pension pIan coverage, pIan type and pIan design, focusing on the role of labor force aging, as well as anticipated developments in the business environment and anticipated changes in public policy

    The mediodorsal thalamus as a higher order thalamic relay nucleus important for learning and decision-making

    Get PDF
    AbstractRecent evidence from monkey models of cognition shows that the magnocellular subdivision of the mediodorsal thalamus (MDmc) is more critical for learning new information than for retention of previously acquired information. Further, consistent evidence in animal models shows the mediodorsal thalamus (MD) contributes to adaptive decision-making. It is assumed that prefrontal cortex (PFC) and medial temporal lobes govern these cognitive processes so this evidence suggests that MD contributes a role in these cognitive processes too. Anatomically, the MD has extensive excitatory cortico-thalamo-cortical connections, especially with the PFC. MD also receives modulatory inputs from forebrain, midbrain and brainstem regions. It is suggested that the MD is a higher order thalamic relay of the PFC due to the dual cortico-thalamic inputs from layer V (‘driver’ inputs capable of transmitting a message) and layer VI (‘modulator’ inputs) of the PFC. Thus, the MD thalamic relay may support the transfer of information across the PFC via this indirect thalamic route. This review summarizes the current knowledge about the anatomy of MD as a higher order thalamic relay. It also reviews behavioral and electrophysiological studies in animals to consider how MD might support the transfer of information across the cortex during learning and decision-making. Current evidence suggests the MD is particularly important during rapid trial-by-trial associative learning and decision-making paradigms that involve multiple cognitive processes. Further studies need to consider the influence of the MD higher order relay to advance our knowledge about how the cortex processes higher order cognition

    A Putative Multiple-Demand System in the Macaque Brain.

    Get PDF
    UNLABELLED: In humans, cognitively demanding tasks of many types recruit common frontoparietal brain areas. Pervasive activation of this "multiple-demand" (MD) network suggests a core function in supporting goal-oriented behavior. A similar network might therefore be predicted in nonhuman primates that readily perform similar tasks after training. However, an MD network in nonhuman primates has not been described. Single-cell recordings from macaque frontal and parietal cortex show some similar properties to human MD fMRI responses (e.g., adaptive coding of task-relevant information). Invasive recordings, however, come from limited prespecified locations, so they do not delineate a macaque homolog of the MD system and their positioning could benefit from knowledge of where MD foci lie. Challenges of scanning behaving animals mean that few macaque fMRI studies specifically contrast levels of cognitive demand, so we sought to identify a macaque counterpart to the human MD system using fMRI connectivity in 35 rhesus macaques. Putative macaque MD regions, mapped from frontoparietal MD regions defined in humans, were found to be functionally connected under anesthesia. To further refine these regions, an iterative process was used to maximize their connectivity cross-validated across animals. Finally, whole-brain connectivity analyses identified voxels that were robustly connected to MD regions, revealing seven clusters across frontoparietal and insular cortex comparable to human MD regions and one unexpected cluster in the lateral fissure. The proposed macaque MD regions can be used to guide future electrophysiological investigation of MD neural coding and in task-based fMRI to test predictions of similar functional properties to human MD cortex. SIGNIFICANCE STATEMENT: In humans, a frontoparietal "multiple-demand" (MD) brain network is recruited during a wide range of cognitively demanding tasks. Because this suggests a fundamental function, one might expect a similar network to exist in nonhuman primates, but this remains controversial. Here, we sought to identify a macaque counterpart to the human MD system using fMRI connectivity. Putative macaque MD regions were functionally connected under anesthesia and were further refined by iterative optimization. The result is a network including lateral frontal, dorsomedial frontal, and insular and inferior parietal regions closely similar to the human counterpart. The proposed macaque MD regions can be useful in guiding electrophysiological recordings or in task-based fMRI to test predictions of similar functional properties to human MD cortex

    50 Years of Test (Un)fairness: Lessons for Machine Learning

    Full text link
    Quantitative definitions of what is unfair and what is fair have been introduced in multiple disciplines for well over 50 years, including in education, hiring, and machine learning. We trace how the notion of fairness has been defined within the testing communities of education and hiring over the past half century, exploring the cultural and social context in which different fairness definitions have emerged. In some cases, earlier definitions of fairness are similar or identical to definitions of fairness in current machine learning research, and foreshadow current formal work. In other cases, insights into what fairness means and how to measure it have largely gone overlooked. We compare past and current notions of fairness along several dimensions, including the fairness criteria, the focus of the criteria (e.g., a test, a model, or its use), the relationship of fairness to individuals, groups, and subgroups, and the mathematical method for measuring fairness (e.g., classification, regression). This work points the way towards future research and measurement of (un)fairness that builds from our modern understanding of fairness while incorporating insights from the past.Comment: FAT* '19: Conference on Fairness, Accountability, and Transparency (FAT* '19), January 29--31, 2019, Atlanta, GA, US

    Functional reorganisation and recovery following cortical lesions: A preliminary study in macaque monkeys.

    Get PDF
    Damage following traumatic brain injury or stroke can often extend beyond the boundaries of the initial insult and can lead to maladaptive cortical reorganisation. On the other hand, beneficial cortical reorganisation leading to recovery of function can also occur. We used resting state FMRI to investigate how cortical networks in the macaque brain change across time in response to lesions to the prefrontal cortex, and how this reorganisation correlated with changes in behavioural performance in cognitive tasks. After prelesion testing and scanning, two monkeys received a lesion to regions surrounding the left principal sulcus followed by periodic testing and scanning. Later, the animals received another lesion to the opposite hemisphere and additional testing and scanning. Following the first lesion, we observed both a behavioural impairment and decrease in functional connectivity, predominantly in frontal-frontal networks. Approximately 8 weeks later, performance and connectivity patterns both improved. Following the second lesion, we observed a further behavioural deficit and decrease in connectivity that showed little recovery. We discuss how different mechanisms including alternate behavioural strategies and reorganisation of specific prefrontal networks may have led to improvements in behaviour. Further work will be needed to confirm these mechanisms.This work was supported by the MRC intramural program MC-A060-5PQ10 (MA, DM, JD, AB), an MRC Career Development Award G0800329 (AM)

    Continued need for non-human primate neuroscience research.

    Get PDF
    Neuroscience research in non-human primates (NHPs) has delivered fundamental knowledge about human brain function as well as some valuable therapies that have improved the lives of human patients with a variety of brain disorders. Research using NHPs, although it is facing serious challenges, continues to complement studies in human volunteers and patients, and will continue to be needed as the burdens of mental health problems and neurodegenerative diseases increase. At the same time, research into the 3Rs is helping to ameliorate the harms experienced by NHPs in experimental procedures, allowing the effective combination of optimal welfare conditions for the NHPs and high quality research

    Interactional positioning and narrative self-construction in the first session of psychodynamic-interpersonal psychotherapy

    Get PDF
    The purpose of this study is to identify possible session one indicators of end of treatment psychotherapy outcome using the framework of three types of interactional positioning; client’s self-positioning, client’s positioning between narrated self and different partners, and the positioning between client and therapist. Three successful cases of 8-session psychodynamic-interpersonal (PI) therapy were selected on the basis of client Beck Depression Inventory scores. One unsuccessful case was also selected against which identified patterns could be tested. The successful clients were more descriptive about their problems and demonstrated active rapport-building, while the therapist used positionings expressed by the client in order to explore the positionings developed between them during therapy. The unsuccessful case was characterized by lack of positive self-comment, minimization of agentic self-capacity, and empathy-disrupting narrative confusions. We conclude that the theory of interactional positioning has been useful in identifying patterns worth exploring as early indicators of success in PI therapy

    The PPARβ/δAgonist GW0742 Relaxes Pulmonary Vessels and Limits Right Heart Hypertrophy in Rats with Hypoxia-Induced Pulmonary Hypertension

    Get PDF
    Copyright: © 2010 Harrington et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedBackground: Pulmonary vascular diseases are increasingly recognised as important clinical conditions. Pulmonary hypertension associated with a range of aetiologies is difficult to treat and associated with progressive morbidity and mortality. Current therapies for pulmonary hypertension include phosphodiesterase type 5 inhibitors, endothelin receptor antagonists, or prostacyclin mimetics. However, none of these provide a cure and the clinical benefits of these drugs individually decline over time. There is, therefore, an urgent need to identify new treatment strategies for pulmonary hypertension. Methodology/Principal Findings: Here we show that the PPARβ/δ agonist GW0742 induces vasorelaxation in systemic and pulmonary vessels. Using tissue from genetically modified mice, we show that the dilator effects of GW0742 are independent of the target receptor PPARβ/δ or cell surface prostacyclin (IP) receptors. In aortic tissue, vascular relaxant effects of GW0742 were not associated with increases in cGMP, cAMP or hyperpolarisation, but were attributed to inhibition of RhoA activity. In a rat model of hypoxia-induced pulmonary hypertension, daily oral dosing of animals with GW0742 (30 mg/kg) for 3 weeks significantly reduced the associated right heart hypertrophy and right ventricular systolic pressure. GW0742 had no effect on vascular remodelling induced by hypoxia in this model. Conclusions/Significance: These observations are the first to show a therapeutic benefit of 'PPARβ/δ' agonists in experimental pulmonary arterial hypertension and provide pre-clinical evidence to favour clinical trials in man.Peer reviewedFinal Published versio

    International primate neuroscience research regulation, public engagement and transparency opportunities

    Get PDF
    Scientific excellence is a necessity for progress in biomedical research. As research becomes ever more international, establishing international collaborations will be key to advancing our scientific knowledge. Understanding the similarities in standards applied by different nations to animal research, and where the differences might lie, is crucial. Cultural differences and societal values will also contribute to these similarities and differences between countries and continents. Our overview is not comprehensive for all species, but rather focuses on non-human primate (NHP) research, involving New World marmosets and Old World macaques, conducted in countries where NHPs are involved in neuroimaging research. Here, an overview of the ethics and regulations is provided to help assess welfare standards amongst primate research institutions. A comparative examination of these standards was conducted to provide a basis for establishing a common set of standards for animal welfare. These criteria may serve to develop international guidelines, which can be managed by an International Animal Welfare and Use Committee (IAWUC). Internationally, scientists have a moral responsibility to ensure excellent care and welfare of their animals, which in turn, influences the quality of their research. When working with animal models, maintaining a high quality of care (“culture of care”) and welfare is essential. The transparent promotion of this level of care and welfare, along with the results of the research and its impact, may reduce public concerns associated with animal experiments in neuroscience research

    Accelerated protein synthesis via one–pot ligation–deselenization chemistry

    Get PDF
    Peptide ligation chemistry has revolutionized protein science by facilitating access to synthetic proteins. Here, we describe the development of additive-free ligation-deselenization chemistry at β-selenoaspartate and γ-selenoglutamate that enables the generation of native polypeptide products on unprecedented timescales. The deselenization step is chemoselective in the presence of unprotected selenocysteine, which is highlighted in the synthesis of selenoprotein K. The power of the methodology is also showcased through the synthesis of three tick-derived thrombin-inhibiting proteins, each of which were assembled, purified, and isolated for biological assays within a few hours. The methodology described here should serve as a powerful means of accessing synthetic proteins, including therapeutic leads, in the future
    corecore