In the century after the Civil War, an economic revolution improved the American standard of living in ways previously unimaginable. Electric lighting, indoor plumbing, motor vehicles, air travel, ...and television transformed households and workplaces. But has that era of unprecedented growth come to an end? Weaving together a vivid narrative, historical anecdotes, and economic analysis,The Rise and Fall of American Growthchallenges the view that economic growth will continue unabated, and demonstrates that the life-altering scale of innovations between 1870 and 1970 cannot be repeated. Robert Gordon contends that the nation's productivity growth will be further held back by the headwinds of rising inequality, stagnating education, an aging population, and the rising debt of college students and the federal government, and that we must find new solutions. A critical voice in the most pressing debates of our time,The Rise and Fall of American Growthis at once a tribute to a century of radical change and a harbinger of tougher times to come.
This study reports a comprehensive empirical investigation of the nature and correlates of anti-mask attitudes during the COVID-19 pandemic. Accumulating evidence underscores the importance of ...facemasks, as worn by the general public, in limiting the spread of infection. Accordingly, mask wearing has become increasingly mandatory in public places such as stores and on public transit. Although the public has been generally adherent to mask wearing, a small but vocal group of individuals refuse to wear masks. Anti-mask protest rallies have occurred in many places throughout the world, sometimes erupting violently. Few empirical studies have examined the relationship between anti-mask attitudes and mask non-adherence and little is known about how such attitudes relate to one another or other factors (e.g., non-adherence to social distancing, anti-vaccination attitudes). To investigate these issues, the present study surveyed 2,078 adults from the US and Canada. Consistent with other surveys, we found that most (84%) people wore masks because of COVID-19. The 16% who did not wear masks scored higher on most measures of negative attitudes towards masks. Network analyses indicated that negative attitudes about masks formed an intercorrelated network, with the central nodes in the network being (a) beliefs that masks are ineffective in preventing COVID-19, and (b) psychological reactance (PR; i.e., an aversion to being forced to wear masks). These central nodes served as links, connecting the network of anti-masks attitudes to negative attitudes toward SARSCoV2 vaccination, beliefs that the threat of COVID-19 has been exaggerated, disregard for social distancing, and political conservatism. Findings regarding PR are important because, theoretically, PR is likely to strengthen other anti-masks attitudes (e.g., beliefs that masks are ineffective) because people with strong PR react with anger and counter-arguments when their beliefs are challenged, thereby leading to a strengthening of their anti-mask beliefs. Implications for improving mask adherence are discussed.
Abstract The laboratory mouse has become the predominant test species in biomedical research. The number of papers that translate or extrapolate data from mouse to human has grown exponentially since ...the year 2000. There are many physiological and anatomical factors to consider in the process of extrapolating data from one species to another. Body temperature is, of course, a critical determinant in extrapolation because it has a direct impact on metabolism, cardiovascular function, drug efficacy, pharmacokinetics of toxins and drugs, and many other effects. While most would consider the thermoregulatory system of mice to be sufficiently stable and predictable as to not be a cause for concern, the thermal physiology of mice does in fact present unique challenges to the biomedical researcher. A variable and unstable core temperature, high metabolic rate, preference for warm temperatures, large surface area: body mass ratio, and high rate of thermal conductance, are some of the key factors of mice that can affect the interpretation and translation of data to humans. It is the intent of this brief review to enlighten researchers studying interspecies translation of biomedical data on the salient facets of the mouse thermal physiology and show how extrapolation in fields such as physiology, psychology, nutrition, pharmacology, toxicology, and pathology.
The need for high-throughput, precise, and meaningful methods for measuring behavior has been amplified by our recent successes in measuring and manipulating neural circuitry. The largest challenges ...associated with moving in this direction, however, are not technical but are instead conceptual: what numbers should one put on the movements an animal is performing (or not performing)? In this review, I will describe how theoretical and data analytical ideas are interfacing with recently-developed computational and experimental methodologies to answer these questions across a variety of contexts, length scales, and time scales. I will attempt to highlight commonalities between approaches and areas where further advances are necessary to place behavior on the same quantitative footing as other scientific fields.
Summary
Aging constitutes the key risk factor for age‐related diseases such as cancer and cardiovascular and neurodegenerative disorders. Human longevity and healthy aging are complex phenotypes ...influenced by both environmental and genetic factors. The fact that genetic contribution to lifespan strongly increases with greater age provides basis for research on which “protective genes” are carried by long‐lived individuals. Studies have consistently revealed FOXO (Forkhead box O) transcription factors as important determinants in aging and longevity. FOXO proteins represent a subfamily of transcription factors conserved from Caenorhabditis elegans to mammals that act as key regulators of longevity downstream of insulin and insulin‐like growth factor signaling. Invertebrate genomes have one FOXO gene, while mammals have four FOXO genes: FOXO1, FOXO3, FOXO4, and FOXO6. In mammals, this subfamily is involved in a wide range of crucial cellular processes regulating stress resistance, metabolism, cell cycle arrest, and apoptosis. Their role in longevity determination is complex and remains to be fully elucidated. Throughout this review, the mechanisms by which FOXO factors contribute to longevity will be discussed in diverse animal models, from Hydra to mammals. Moreover, compelling evidence of FOXOs as contributors for extreme longevity and health span in humans will be addressed.
Allergic asthma is caused by Th2-cell-type cytokines in response to allergen exposure. Type 2 innate lymphoid cells (ILC2s) are a newly identified subset of immune cells that, along with Th2 cells, ...contribute to the pathogenesis of asthma by producing copious amounts of IL-5 and IL-13, which cause eosinophilia and airway hyperreactivity (AHR), a cardinal feature of asthma. ILC2s express ICOS, a T cell costimulatory molecule with a currently unknown function. Here we showed that a lack of ICOS on murine ILC2s and blocking the ICOS:ICOS-ligand interaction in human ILC2s reduced AHR and lung inflammation. ILC2s expressed both ICOS and ICOS-ligand, and the ICOS:ICOS-ligand interaction promoted cytokine production and survival in ILC2s through STAT5 signaling. Thus, ICOS:ICOS-ligand signaling pathway is critically involved in ILC2 function and homeostasis.
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•Human and murine ILC2s express both ICOS and ICOS-ligand•The ICOS:ICOS-ligand interaction is required for survival and efficient function of ILC2s•STAT5 signaling is impaired in the absence of ICOS
Akbari and colleagues show the requirement of Inducible T cell Costimulator (ICOS) for the survival and efficient cytokine production of type 2 innate lymphoid cells (ILC2s), which are key players in the pathogenesis of allergic asthma.
Targeting immune checkpoints such as programmed cell death protein 1 (PD1), programmed cell death 1 ligand 1 (PDL1) and cytotoxic T lymphocyte antigen 4 (CTLA4) has achieved noteworthy benefit in ...multiple cancers by blocking immunoinhibitory signals and enabling patients to produce an effective antitumour response. Inhibitors of CTLA4, PD1 or PDL1 administered as single agents have resulted in durable tumour regression in some patients, and combinations of PD1 and CTLA4 inhibitors may enhance antitumour benefit. Numerous additional immunomodulatory pathways as well as inhibitory factors expressed or secreted by myeloid and stromal cells in the tumour microenvironment are potential targets for synergizing with immune checkpoint blockade. Given the breadth of potential targets in the immune system, critical questions to address include which combinations should move forward in development and which patients will benefit from these treatments. This Review discusses the leading drug targets that are expressed on tumour cells and in the tumour microenvironment that allow enhancement of the antitumour immune response.
The microsatellite instable (MSI) subset of colorectal cancer exhibits an active Th1/CTL immune microenvironment, probably due to recognition of a high number of tumor neoantigens. However, the high ...expression of checkpoint molecules PD-1, PD-L1, CTLA-4, LAG-3, and IDO in MSI colorectal cancer distinguishes MSI from microsatellite stable colorectal cancer and creates an immunosuppressive microenvironment that may help MSI tumors evade immune destruction by the infiltrating immune cells. Though colorectal cancer does not have a good response rate to PD-1 pathway immunotherapy, these results suggest that the MSI subset of colorectal cancer is a particularly good candidate for checkpoint immunotherapy.
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