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"Carroll, Christopher"
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Papa's backpack
A bear cub understands that because Papa's a soldier, he sometimes must go, but imagines what it'd be like to stay near by riding in Papa's backpack.
Book
Differential incorporation of SUN-domain proteins into LINC complexes is coupled to gene expression
LInkers of Nucleoskeleton and Cytoskeleton (LINC) complexes, composed of SUN and KASH-domain proteins, span the nuclear envelope and physically connect the nuclear interior to cytoskeletal elements. Most human cells contain two SUN proteins, Sun1 and Sun2, and several KASH-proteins suggesting that multiple functionally distinct LINC complexes co-exist in the nuclear envelope. We show here, however, that while Sun1 and Sun2 in HeLa cells are each able to bind KASH-domains, Sun1 is more efficiently incorporated into LINC complexes under normal growth conditions. Furthermore, the balance of Sun1 and Sun2 incorporated into LINC complexes is cell type-specific and is correlated with SRF/Mkl1-dependent gene expression. In addition, we found that Sun1 has a LINC complex-independent role in transcriptional control, possibly by regulating the SRF/Mkl1 pathway. Together, these data reveal novel insights into the mechanisms of LINC complex regulation and demonstrate that Sun1 modulates gene expression independently of its incorporation into LINC complexes.
Journal Article
How Large Are Housing and Financial Wealth Effects? A New Approach
This paper presents a simple new method for measuring \"wealth effects\" on aggregate consumption. The method exploits the stickiness of consumption growth (sometimes interpreted as reflecting consumption \"habits\") to distinguish between immediate and eventual wealth effects. In U.S. data, we estimate that the immediate (next quarter) marginal propensity to consume from a $1 change in housing wealth is about 2 cents, with a final eventual effect around 9 cents, substantially larger than the effect of shocks to financial wealth. We argue that our method is preferable to cointegration-based approaches, because neither theory nor evidence supports faith in the existence of a stable cointegrating vector.
Journal Article
A worked example of \best fit\ framework synthesis: A systematic review of views concerning the taking of some potential chemopreventive agents
Background
A variety of different approaches to the synthesis of qualitative data are advocated in the literature. The aim of this paper is to describe the application of a pragmatic method of qualitative evidence synthesis and the lessons learned from adopting this \"best fit\" framework synthesis approach.
Methods
An evaluation of framework synthesis as an approach to the qualitative systematic review of evidence exploring the views of adults to the taking of potential agents within the context of the primary prevention of colorectal cancer.
Results
Twenty papers from North America, Australia, the UK and Europe met the criteria for inclusion. Fourteen themes were identified
a priori
from a related, existing conceptual model identified in the literature, which were then used to code the extracted data. Further analysis resulted in the generation of a more sophisticated model with additional themes. The synthesis required a combination of secondary framework and thematic analysis approaches and was conducted within a health technology assessment timeframe.
Conclusion
The novel and pragmatic \"best fit\" approach to framework synthesis developed and described here was found to be fit for purpose. Future research should seek to test further this approach to qualitative data synthesis.
Journal Article
The distribution of wealth and the marginal propensity to consume
In a model calibrated to match micro- and macroeconomic evidence on household income dynamics, we show that a modest degree of heterogeneity in household preferences or beliefs is sufficient to match empirical measures of wealth inequality in the United States. The heterogeneity-augmented model's predictions are consistent with microeconomic evidence that suggests that the annual marginal propensity to consume (MPC) is much larger than the roughly 0.04 im- plied by commonly used macroeconomic models (even ones including some heterogeneity). The high MPC arises because many consumers hold little wealth despite having a strong precautionary motive. Our model also plausibly predicts that the aggregate MPC can differ greatly depending on how the shock is distributed across households (depending, e.g., on their wealth, or employment status).
Journal Article
Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3
Nutrient availability is the major regulator of life and reproduction, and a complex cellular signaling network has evolved to adapt organisms to fasting. These sensor pathways monitor cellular energy metabolism, especially mitochondrial ATP production and NAD
+
/NADH ratio, as major signals for nutritional state. We hypothesized that these signals would be modified by mitochondrial respiratory chain disease, because of inefficient NADH utilization and ATP production. Oral administration of nicotinamide riboside (NR), a vitamin B3 and NAD
+
precursor, was previously shown to boost NAD
+
levels in mice and to induce mitochondrial biogenesis. Here, we treated mitochondrial myopathy mice with NR. This vitamin effectively delayed early‐ and late‐stage disease progression, by robustly inducing mitochondrial biogenesis in skeletal muscle and brown adipose tissue, preventing mitochondrial ultrastructure abnormalities and mtDNA deletion formation. NR further stimulated mitochondrial unfolded protein response, suggesting its protective role in mitochondrial disease. These results indicate that NR and strategies boosting NAD
+
levels are a promising treatment strategy for mitochondrial myopathy.
Synopsis
Nicotinamide riboside (vitamin B3) delays the progression of mitochondrial myopathy by preventing pathology‐associated mitochondrial ultrastructure, improving mitochondrial DNA stability and further stimulating mitochondrial unfolded protein response.
Nicotinamide riboside, vitamin B3, delays the progression of mitochondrial myopathy.
Nicotinamide riboside cures pathology‐associated mitochondrial ultrastructure.
Nicotinamide riboside improves mitochondrial DNA stability.
Mitochondrial disease induces mitochondrial unfolded protein response, further enhanced by nicotinamide riboside.
Nicotinamide riboside is a promising treatment for adult‐onset mitochondrial myopathy.
Graphical Abstract
Nicotinamide riboside (vitamin B3) delays the progression of mitochondrial myopathy by preventing pathology‐associated mitochondrial ultrastructure, improving mitochondrial DNA stability and further stimulating mitochondrial unfolded protein response.
Journal Article
The use of machine learning and artificial intelligence within pediatric critical care
The field of pediatric critical care has been hampered in the era of precision medicine by our inability to accurately define and subclassify disease phenotypes. This has been caused by heterogeneity across age groups that further challenges the ability to perform randomized controlled trials in pediatrics. One approach to overcome these inherent challenges include the use of machine learning algorithms that can assist in generating more meaningful interpretations from clinical data. This review summarizes machine learning and artificial intelligence techniques that are currently in use for clinical data modeling with relevance to pediatric critical care. Focus has been placed on the differences between techniques and the role of each in the clinical arena. The various forms of clinical decision support that utilize machine learning are also described. We review the applications and limitations of machine learning techniques to empower clinicians to make informed decisions at the bedside.
Impact
Critical care units generate large amounts of under-utilized data that can be processed through artificial intelligence.
This review summarizes the machine learning and artificial intelligence techniques currently being used to process clinical data.
The review highlights the applications and limitations of these techniques within a clinical context to aid providers in making more informed decisions at the bedside.
Journal Article
Multisystem Inflammatory Syndrome in U.S. Children and Adolescents
This report describes the epidemiology and clinical course of patients younger than 21 years of age from 26 states who had multisystem inflammatory syndrome. Many were infected with SARS-CoV-2 at least 1 to 2 weeks before syndrome onset. The median age of the patients was 8.3 years, and 73% were previously healthy.
Journal Article
Multisystem Inflammatory Syndrome in Children — Initial Therapy and Outcomes
An analysis of surveillance data on inpatients younger than 21 years of age who had multisystem inflammatory syndrome in children and were hospitalized between March 15 and October 31, 2020, showed that initial treatment with IVIG plus glucocorticoids was associated with a lower risk of cardiovascular dysfunction and a lower incidence of adjunctive therapy use than IVIG alone.
Journal Article