The Development of the Neoclassical Tradition in Labor Economics

This essay on labor economics examines neoclassical theory\u27s rise to ascendancy following the second World War, with a secondary focus on the relative decline but continued influence of institutionalist economic theory. The authors describe the evolution of institutional and neoclassical theory from the late nineteenth to mid-twentieth centuries, examine some early intellectual debates between the two camps, briefly describe the work of neoclassical labor economics pioneers, and look at major developments over the past 30 years. They argue that neoclassical economists\u27 increasing intellectual breadth and influence in public policy have led them to pay closer attention to issues that have long been of concern to institutionalists and neoinstitutionalists

"Making Safety Happen" Through Probabilistic Risk Assessment at NASA

NASA is using Probabilistic Risk Assessment (PRA) as one of the tools in its Safety & Mission Assurance (S&MA) tool belt to identify and quantify risks associated with human spaceflight. This paper discusses some of the challenges and benefits associated with developing and using PRA for NASA human space programs. Some programs have entered operation prior to developing a PRA, while some have implemented PRA from the start of the program. It has been observed that the earlier a design change is made in the concept or design phase, the less impact it has on cost and schedule. Not finding risks until the operation phase yields much costlier design changes and major delays, which can result in discussions of just accepting the risk. Risk contributors identified by PRA are not just associated with hardware failures. They include but are not limited to crew fatality due to medical causes, the environment the vehicle and crew are exposed to, the software being used, and the reliability of the crew performing required actions. Some programs have entered operation prior to developing a PRA, and while PRA can still provide a benefit for operations and future design trades, the benefit of implementing PRA from the start of the program provides the added benefit of informing design and reducing risk early in program development. Currently, NASAs International Space Station (ISS) program is in its 20th year of on-orbit operations around the Earth and has several new programs in the design phase preparing to enter the operation phase all of which have active (or living) PRAs. These programs incorporate PRA as part of their Risk-Informed, Decision-Making (RIDM) process. For new NASA human spaceflight programs discussion begins with mission concept, establishing requirements, forming the PRA team, and continues through the design cycles into the operational phase. Several examples of PRA related applications and observed lessons are included

Fluorescence-Guided Stereotactic Biopsy: A Proof-of-Concept Study

Introduction: Histopathological diagnoses are often necessary for treating neuro-oncology patients. However, stereotactic biopsy (STB), a common method for obtaining tissue from deep or eloquent brain regions, fails to yield diagnostic tissue in approximately 10% of cases. This can delay initiation of treatment and may result in further invasive procedures for patients. Here, we evaluate if coupling in vivo optical imaging with a STB system can identify diagnostic tissue at the time of biopsy. Methods: A minimally invasive fiber optic imaging system was developed by coupling a 0.65mm diameter fiber optic fluorescence microendoscope to a STB system. Human glioma cells were transduced for stable expression of blue fluorescent protein (U251-BFP) and utilized for in vitro and in vivo experiments. In vitro, blue fluorescence was confirmed, and tumor cell delineation by sodium fluorescein (FNa) was quantified with fluorescence microscopy. Rodent xenografts implanted with U251-BFP cells (n=4) were utilized for in vivo experiments. Five weeks post-implantation, xenografts received 5-10mg/kg intravenous FNa and underwent craniotomies overlying the tumor implantation site and contralateral normal brain. A clinical STB needle containing our 0.65mm imaging fiber was passed through each craniotomy and images were collected. Fluorescence images from regions of interest (ROI) ipsilateral and contralateral to tumor implantation were analyzed. Results: Live-cell fluorescence imaging confirmed blue fluorescence from transduced tumor cells and revealed a strong correlation between tumor cells quantified by blue fluorescence and FNa contrast (R2=0.91, p\u3c0.001). Normalized to background, in vivo FNa fluorescence intensity was significantly greater from tumor regions, verified by blue fluorescence, compared to contralateral brain in all animals (60.65± 17.35 %, p\u3c0.001). Fluorescein fluorescence was not significantly greater from the tumor margin compared to normal brain (p =0.096). Biopsies obtained from regions of strong fluorescein contrast were histologically consistent with tumor. Conclusion: We found in vivo fluorescence imaging with a STB needle containing a submillimeter diameter fluorescence microendoscope provided direct visualization of neoplastic tissue in an animal brain tumor model prior to biopsy. This was confirmed in vivo and by post-hoc histological assessment. In vivo fluorescence guidance may improve the diagnostic yield of stereotactic biopsies

Methamphetamine administration targets multiple immune subsets and induces phenotypic alterations suggestive of immunosuppression.

Methamphetamine (Meth) is a widely abused stimulant and its users are at increased risk for multiple infectious diseases. To determine the impact of meth on the immune system, we utilized a murine model that simulates the process of meth consumption in a typical addict. Our phenotypic analysis of leukocytes from this dose escalation model revealed that meth affected key immune subsets. Meth administration led to a decrease in abundance of natural killer (NK) cells and the remaining NK cells possessed a phenotype suggesting reduced responsiveness. Dendritic cells (DCs) and Gr-1(high) monocytes/macrophages were also decreased in abundance while Gr-1(low) monocytes/macrophages appear to show signs of perturbation. CD4 and CD8 T cell subsets were affected by methamphetamine, both showing a reduction in antigen-experienced subsets. CD4 T cells also exhibited signs of activation, with increased expression of CD150 on CD226-expressing cells and an expansion of KLRG1(+), FoxP3(-) cells. These results exhibit that meth has the ability to disrupt immune homeostasis and impact key subsets of leukocytes which may leave users more vulnerable to pathogens

Integrated results from the COPERNICUS and GALILEO studies.

OBJECTIVES: To report on the efficacy and safety of intravitreal aflibercept in patients with macular edema secondary to central retinal vein occlusion (CRVO) in an integrated analysis of COPERNICUS and GALILEO. PATIENTS AND METHODS: Patients were randomized to receive intravitreal aflibercept 2 mg every 4 weeks or sham injections until week 24. From week 24 to week 52, all intravitreal aflibercept-treated patients in both studies and sham-treated patients in COPERNICUS were eligible to receive intravitreal aflibercept based on prespecified criteria. In GALILEO, sham-treated patients continued to receive sham treatment through week 52. RESULTS: At week 24, mean gain in best-corrected visual acuity and mean reduction in central retinal thickness were greater for intravitreal aflibercept-treated patients compared with sham, consistent with individual trial results. At week 52, after 6 months of intravitreal aflibercept as-needed treatment in COPERNICUS, patients originally randomized to sham group experienced visual and anatomic improvements but did not improve to the extent of those initially treated with intravitreal aflibercept, while the sham group in GALILEO did not improve over week 24 mean best-corrected visual acuity scores. Ocular serious adverse events occurred in CONCLUSION: This analysis of integrated data from COPERNICUS and GALILEO confirmed that intravitreal aflibercept is an effective treatment for macular edema following CRVO

Insight Into the Molecular Mechanisms for Microcystin Biodegradation in Lake Erie and Lake Taihu

Microcystins are potent hepatotoxins that are frequently detected in fresh water lakes plagued by toxic cyanobacteria. Microbial biodegradation has been referred to as the most important avenue for removal of microcystin from aquatic environments. The biochemical pathway most commonly associated with the degradation of microcystin is encoded by the mlrABCD (mlr) cassette. The ecological significance of this pathway remains unclear as no studies have examined the expression of these genes in natural environments. Six metatranscriptomes were generated from microcystin-producing Microcystis blooms and analyzed to assess the activity of this pathway in environmental samples. Seventy-eight samples were collected from Lake Erie, United States/Canada and Lake Tai (Taihu), China, and screened for the presence of mlr gene transcripts. Read mapping to the mlrcassette indicated transcripts for these genes were absent, with only 77 of the collective 3.7 billion reads mapping to any part of the mlr cassette. Analysis of the assembled metatranscriptomes supported this, with only distantly related sequences identified as mlrABC-like. These observations were made despite the presence of microcystin and over 500,000 reads mapping to the mcy cassette for microcystin production. Glutathione S-transferases and alkaline proteases have been previously hypothesized to be alternative pathways for microcystin biodegradation, and expression of these genes was detected across space and time in both lakes. While the activity of these alternative pathways needs to be experimentally confirmed, they may be individually or collectively more important than mlr genes in the natural environment. Importantly, the lack of mlr expression could indicate microcystin biodegradation was not occurring in the analyzed samples. This study raises interesting questions about the ubiquity, specificity and locality of microcystin biodegradation, and highlights the need for the characterization of relevant mechanisms in natural communities to understand the fate of microcystin in the environment and risk to public health

Author Correction: Longitudinal assessment of tumor development using cancer avatars derived from genetically engineered pluripotent stem cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper