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Methaemoglobin is a form of haemoglobin with oxidised ferric (+3) iron rather than ferrous (+2) iron, which causes a leftward shift in the oxyhaemoglobin dissociation curve and prevents oxygen delivery. Anaesthesiologists need to be familiar with this differential diagnosis for hypoxia given the use of drugs in the perioperative setting known to induce methaemoglobinaemia, including benzocaine and lidocaine, antibiotics such as dapsone and anaesthetic gases, including nitric oxide. This case report details an interesting case of symptomatic methaemoglobinaemia in the perioperative period in the setting of dapsone use and an erector spinae block performed with ropivacaine.

The COVID-19 pandemic created a unique opportunity to explore the use of Technology Enabled Care Services (TECS), which remains novel for many service providers. This study assesses the factors that affect adaptation to remote monitoring of patients after upper-limb trauma injury. A standardised risk-stratified screening tool is further developed here to support clinical staff in both the determination of appropriate use of TECS and the optimisation of patient care.1: To explore the patient and injury factors that determine the appropriate use of TECS for patients with upper-limb injury. 2: To use these findings to refine a standardised screening tool for the appropriate choice of follow-up format.A retrospective review of patient management was undertaken across three NHS upper-limb trauma units during the first UK COVID-19 lockdown. Data were collected, and themes were analysed across a number of predetermined categories. This was underpinned by a review of contemporary policy guidance and literature.A total of 85% of patients were offered an appropriate format of follow-up; this was defined by the ability to achieve desired patient-clinician goals and lack of complications. Key factors in determining appropriate follow-up included extent of injury, mental health considerations, and the need for face-to-face (F2F) assessment and treatment.Study findings demonstrate consistency between units in the factors determining the appropriate use of TECS. The refined screening tool provides a risk-stratified, standardised approach to the choice of follow-up format, F2F or TECS. It is hoped that this will support future clinical decision-making processes to ensure optimal patient care.

Artificial intelligence (AI) could have the potential to accurately classify mammograms according to the presence or absence of radiological signs of breast cancer, replacing or supplementing human readers (radiologists). The UK National Screening Committee's assessments of the use of AI systems to examine screening mammograms continues to focus on maximising benefits and minimising harms to women screened, when deciding whether to recommend the implementation of AI into the Breast Screening Programme in the UK. Maintaining or improving programme specificity is important to minimise anxiety from false positive results. When considering cancer detection, AI test sensitivity alone is not sufficiently informative, and additional information on the spectrum of disease detected and interval cancers is crucial to better understand the benefits and harms of screening. Although large retrospective studies might provide useful evidence by directly comparing test accuracy and spectrum of disease detected between different AI systems and by population subgroup, most retrospective studies are biased due to differential verification (ie, the use of different reference standards to verify the target condition among study participants). Enriched, multiple-reader, multiple-case, test set laboratory studies are also biased due to the laboratory effect (ie, radiologists' performance in retrospective, laboratory, observer studies is substantially different to their performance in a clinical environment). Therefore, assessment of the effect of incorporating any AI system into the breast screening pathway in prospective studies is required as it will provide key evidence for the effect of the interaction of medical staff with AI, and the impact on women's outcomes.

Somatic hypermutation at antibody loci affects both deoxyadenosine-deoxythymidine (A/T) and deoxycytidine-deoxyguanosine (C/G) pairs. Deamination of C to deoxyuridine (U) by activation-induced deaminase (AID) explains how mutation at C/G pairs is potentiated. Mutation at A/T pairs is triggered during the initial stages of repair of AID-generated U lesions and occurs through an as yet unknown mechanism in which polymerase η has a major role. Recent evidence confirms that human polymerase η can act as a reverse transcriptase. Here, we compare the popular suggestion of mutation at A/T pairs through nucleotide mispairing (owing to polymerase error) during short-patch repair synthesis with the alternative proposal of mutation at A/T pairs through RNA editing and RNA-directed DNA repair.

Supplementary methods and Figures Supplementary Figure 1. Effect of cerdulatinib on Immobilised anti-IgM mediated signaling Supplementary Figure 2. Effect of cerdulatinib on soluble anti-IgM mediated signaling Supplementary Figure 3. Effect of cerdulatinib on Immobilised anti-IgD mediated signaling Supplementary Figure 4. Effect of cerdulatinib on soluble anti-IgD mediated signaling Supplementary Figure 5. Effect of cerdulatinib on anti-IgM induced calcium flux and IL-4 induced surface marker expression Supplementary Figure 6. Representative phosflow plots Supplementary Figure 7. Cerdulatinib overcomes the protective effect of BCR-stimulation and IL- 4/CD40L. Supplementary Figure 8. Mcl-1 and Bcl-XL but not Bcl-2 are downregulated by cerdulatinib Supplementary Figure 9. Effect of cerdulatinib on MCL-1 and BCL-XL mRNA expression

Contains Supplemental Table 1, drosophila diet fatty acid composition. Supplemental Table 2, mouse diet composition. Supplemental Table 3, mouse diet fatty acid composition. Supplemental Table 4, incorporation of exogenous fatty acids into murine colonic crypt membrane phospholipids. Supplemental Table 5, incorporation of exogenous corn oil fatty acids into Drosophila gut membrane phospholipids.

This file contains supplementary data showing phenotypic/cytokine/chemokine changes in immune cell population following stimulation/tumour inoculation. The data also demonstrate that monocyte and neutrophil are not required for mAb mediated deletion of target cell in adoptive transfer model.

Purpose:In chronic lymphocytic leukemia (CLL), disease progression associates with surface IgM (sIgM) levels and signaling capacity. These are variably downmodulated in vivo and recover in vitro, suggesting a reversible influence of tissue-located antigen. Therapeutic targeting of sIgM function via ibrutinib, an inhibitor of Bruton tyrosine kinase (BTK), causes inhibition and tumor cell redistribution into the blood, with significant clinical benefit. Circulating CLL cells persist in an inhibited state, offering a tool to investigate the effects of drug on BTK-inhibited sIgM.Experimental Design:We investigated the consequences of ibrutinib therapy on levels and function of sIgM in circulating leukemic cells of patients with CLL.Results:At week 1, there was a significant increase of sIgM expression (64% increase from pretherapy) on CLL cells either recently released from tissue or persisting in blood. In contrast, surface IgD (sIgD) and a range of other receptors did not change. SIgM levels remained higher than pretherapy in the following 3 months despite gradual cell size reduction and ongoing autophagy and apoptotic activity. Conversely, IgD and other receptors did not increase and gradually declined. Recovered sIgM was fully N-glycosylated, another feature of escape from antigen, and expression did not increase further during culture in vitro. The sIgM was fully capable of mediating phosphorylation of SYK, which lies upstream of BTK in the B-cell receptor pathway.Conclusions:This specific IgM increase in patients underpins the key role of tissue-based engagement with antigen in CLL, confirms the inhibitory action of ibrutinib, and reveals dynamic adaptability of CLL cells to precision monotherapy.See related commentary by Burger, p. 2372

Purpose: B-cell receptor (BCR)–associated kinase inhibitors, such as ibrutinib, have revolutionized the treatment of chronic lymphocytic leukemia (CLL). However, these agents are not curative, and resistance is already emerging in a proportion of patients. IL4, expressed in CLL lymph nodes, can augment BCR signaling and reduce the effectiveness of BCR kinase inhibitors. Therefore, simultaneous targeting of the IL4- and BCR signaling pathways by cerdulatinib, a novel dual Syk/JAK inhibitor currently in clinical trials (NCT01994382), may improve treatment responses in patients.Experimental Design: PBMCs from patients with CLL were treated in vitro with cerdulatinib alone or in combination with venetoclax. Cell death, chemokine, and cell signaling assay were performed and analyzed by flow cytometry, immunoblotting, q-PCR, and ELISA as indicated.Results: At concentrations achievable in patients, cerdulatinib inhibited BCR- and IL4-induced downstream signaling in CLL cells using multiple readouts and prevented anti-IgM- and nurse-like cell (NLC)–mediated CCL3/CCL4 production. Cerdulatinib induced apoptosis of CLL cells, in a time- and concentration-dependent manner, and particularly in IGHV-unmutated samples with greater BCR signaling capacity and response to IL4, or samples expressing higher levels of sIgM, CD49d+, or ZAP70+. Cerdulatinib overcame anti-IgM, IL4/CD40L, or NLC-mediated protection by preventing upregulation of MCL-1 and BCL-XL; however, BCL-2 expression was unaffected. Furthermore, in samples treated with IL4/CD40L, cerdulatinib synergized with venetoclax in vitro to induce greater apoptosis than either drug alone.Conclusions: Cerdulatinib is a promising therapeutic for the treatment of CLL either alone or in combination with venetoclax, with the potential to target critical survival pathways in this currently incurable disease. Clin Cancer Res; 23(9); 2313–24. ©2016 AACR.

Contains Supplemental Figure 1, photomicrographs of cells demonstrating the method for determining quantitative pERK levels. Supplemental Figure 2, pERK, ERK, and Ras western images. Supplemental Figure 3, charts representing data from FLIM-FRET experiments on corn oil fed drosophila.

Ras signaling originates from transient nanoscale compartmentalized regions of the plasma membrane composed of specific proteins and lipids. The highly specific lipid composition of these nanodomains, termed nanoclusters, facilitates effector recruitment and therefore influences signal transduction. This suggests that Ras nanocluster proteolipid composition could represent a novel target for future chemoprevention interventions. There is evidence that consumption of fish oil containing long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) such as eicosapentaenoic acid (EPA, 20:5Δ5,8,11,14,17) and docosahexaenoic acid (DHA, 22:6Δ4,7,10,13,16,19) may reduce colon cancer risk in humans, yet the mechanism underlying this effect is unknown. Here, we demonstrate that dietary n-3 PUFA reduce the lateral segregation of cholesterol-dependent and -independent nanoclusters, suppressing phosphatidic acid-dependent oncogenic KRas effector interactions, via their physical incorporation into plasma membrane phospholipids. This results in attenuation of oncogenic Ras-driven colonic hyperproliferation in both Drosophila and murine models. These findings demonstrate the unique properties of dietary n-3 PUFA in the shaping of Ras nanoscale proteolipid complexes and support the emerging role of plasma membrane-targeted therapies.Significance: The influence of dietary long chain n-3 polyunsaturated fatty acids on plasma membrane protein nanoscale organization and KRas signaling supports development of plasma membrane-targeted therapies in colon cancer.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/14/3899/F1.large.jpg. Cancer Res; 78(14); 3899–912. ©2018 AACR.

Tumors routinely attract and co-opt macrophages to promote their growth, angiogenesis, and metastasis. Macrophages are also the key effector cell for mAb therapies. Here we report that the tumor microenvironment creates an immunosuppressive signature on tumor-associated macrophages (TAM), which favors expression of inhibitory rather than activating Fcγ receptors (FcγR), thereby limiting the efficacy of mAb immunotherapy. We assessed a panel of TLR and STING agonists (a) for their ability to reprogram macrophages to a state optimal for mAb immunotherapy. Both STINGa and TLRa induced cytokine release, modulated FcγR expression, and augmented mAb-mediated tumor cell phagocytosis in vitro. However, only STINGa reversed the suppressive FcγR profile in vivo, providing strong adjuvant effects to anti-CD20 mAb in murine models of lymphoma. Potent adjuvants like STINGa, which can improve FcγR activatory:inhibitory (A:I) ratios on TAM, are appealing candidates to reprogram TAM and curb tumor-mediated immunosuppression, thereby empowering mAb efficacy. Cancer Res; 77(13); 3619–31. ©2017 AACR.

Supplementary data

Supplementary Tables S1-S2 and Figures S1-S4 with legends

Contains the legend text for supplemental figures 1, quantitative pERK analysis images.Supplemental figures 2, pERK Western. Supplemental figures 3, Drosophila corn oil FLIM-FRET.

To determine differences in glucose control and cardiovascular disease risk factors following three weeks of added soda, 100% fruit juice, or water in apparently healthy, college-aged adults.Thirty-six adults (18 males; 18 females) between the ages of 18 and 30 years of age.A 3-arm randomized controlled parallel-arm trial; at baseline and after three weeks consuming the assigned beverage, participants completed glucose control and cardiovascular disease risk factor assessments.There were no significant differences between beverage conditions for glucose control or cardiovascular disease risk factors (ps0.05). There were no significant changes in caloric intake or differences in caloric intake between conditions,In healthy, young adults, under free-living conditions, short-term consumption of two commercially packaged servings of SBs did not lead to significant glucose control or cardiovascular disease risk factor changes, indicating potential compensation and/or resilience to negative short-term effects.

Determination of the rheological behavior of polymer magnetic composites is required for real-time industrial processing and incorporating advance material feedback loops. However, the rheological behavior in the presence of an alternating magnetic field (AMF) has many technical challenges with respect to unwanted induction of nearby electronics and testing probes. For the first time, a custom-made magneto-rheometer is designed to quantitate viscoelastic adhesives susceptible to alternating magnetic fields (AMFs). The dynamic viscosity, complex modulus, and temperature profiles are correlated with the cumulative AMF exposure, thermal conductivity, particle loading and nature of non-ferrous support materials. Magnetoadhesive composites reached the gelation point in less than 1 min after AMF exposure. Epoxy resins exceeded 11 MPa shear modulus at strains of

OBJECTIVE Historically, preoperative planning for functional neurosurgery has depended on the indirect localization of target brain structures using visible anatomical landmarks. However, recent technological advances in neuroimaging have permitted marked improvements in MRI-based direct target visualization, allowing for refinement of “first-pass” targeting. The authors reviewed studies relating to direct MRI visualization of the most common functional neurosurgery targets (subthalamic nucleus, globus pallidus, and thalamus) and summarize sequence specifications for the various approaches described in this literature. METHODS The peer-reviewed literature on MRI visualization of the subthalamic nucleus, globus pallidus, and thalamus was obtained by searching MEDLINE. Publications examining direct MRI visualization of these deep brain stimulation targets were included for review. RESULTS A variety of specialized sequences and postprocessing methods for enhanced MRI visualization are in current use. These include susceptibility-based techniques such as quantitative susceptibility mapping, which exploit the amount of tissue iron in target structures, and white matter attenuated inversion recovery, which suppresses the signal from white matter to improve the distinction between gray matter nuclei. However, evidence confirming the superiority of these sequences over indirect targeting with respect to clinical outcome is sparse. Future targeting may utilize information about functional and structural networks, necessitating the use of resting-state functional MRI and diffusion-weighted imaging. CONCLUSIONS Specialized MRI sequences have enabled considerable improvement in the visualization of common deep brain stimulation targets. With further validation of their ability to improve clinical outcomes and advances in imaging techniques, direct visualization of targets may play an increasingly important role in preoperative planning.

STFC are acknowledged for supporting the “Curation and Preliminary Examination of the Winchcombe Carbonaceous Chondrite Fall” project (ST/V000799/1), and Natural History Museum staff for curatorial support. Oxygen isotope studies at the Open University are funded by a consolidated grant from the Science and Technology Facilities Council (STFC), UK GRANT NUMBER: ST/T000228/1 (IAF, RCG, JM, MA), and STFC studentship NUMBER: ST/S505614/1 (RF). As part of an integrated consortium study, we have undertaken O, Cd, Cr, Si, Te, Ti, and Zn whole rock isotopic measurements of the Winchcombe CM2 meteorite. δ66Zn values determined for two Winchcombe aliquots are +0.29 ± 0.05‰ (2SD) and +0.45 ± 0.05‰ (2SD). The difference between these analyses likely reflects sample heterogeneity. Zn isotope compositions for Winchcombe show excellent agreement with published CM2 data. δ114Cd for a single Winchcombe aliquot is +0.29 ± 0.04‰ (2SD), which is close to a previous result for Murchison. δ130Te values for three aliquots gave indistinguishable results, with a mean value of +0.62 ± 0.01‰ (2SD) and are essentially identical to published values for CM2s. ε53Cr and ε54Cr for Winchcombe are 0.319 ± 0.029 (2SE) and 0.775 ± 0.067 (2SE), respectively. Based on its Cr isotopic composition, Winchcombe plots close to other CM2 chondrites. ε50Ti and ε46Ti values for Winchcombe are 3.21 ± 0.09 (2SE) and 0.46 ± 0.08 (2SE), respectively, and are in line with recently published data for CM2s. The δ30Si composition of Winchcombe is −0.50 ± 0.06‰ (2SD, n = 11) and is essentially indistinguishable from measurements obtained on other CM2 chondrites. In conformity with petrographic observations, oxygen isotope analyses of both bulk and micromilled fractions from Winchcombe clearly demonstrate that its parent body experienced extensive aqueous alteration. The style of alteration exhibited by Winchcombe is consistent with relatively closed system processes. Analysis of different fractions within Winchcombe broadly support the view that, while different lithologies within an individual CM2 meteorite can be highly variable, each meteorite is characterized by a predominant alteration type. Mixing of different lithologies within a regolith environment to form cataclastic matrix is supported by oxygen isotope analysis of micromilled fractions from Winchcombe. Previously unpublished bulk oxygen isotope data for 12 CM2 chondrites, when combined with published data, define a well‐constrained regression line with a slope of 0.77. Winchcombe analyses define a more limited linear trend at the isotopically heavy, more aqueously altered, end of the slope 0.77 CM2 array. The CM2 slope 0.77 array intersects the oxygen isotope field of CO3 falls, indicating that the unaltered precursor material to the CMs was essentially identical in oxygen isotope composition to the CO3 falls. Our data are consistent with earlier suggestions that the main differences between the CO3s and CM2s reflect differing amounts of water ice that co‐accreted into their respective parent bodies, being high in the case of CM2s and low in the case of CO3s. The small difference in Si isotope compositions between the CM and CO meteorites can be explained by different proportions of matrix versus refractory silicates. CMs and COs may also be indistinguishable with respect to Ti and Cr isotopes; however, further analysis is required to test this possibility. The close relationship between CO3 and CM2 chondrites revealed by our data supports the emerging view that the snow line within protoplanetary disks marks an important zone of planetesimal accretion. Publisher PDF

Using odors to find food and mates is one of the most ancient and highly conserved behaviors. Arthropods from flies to moths to crabs use broadly similar strategies to navigate toward odor sources—such as integrating flow information with odor information, comparing odor concentration across sensors, and integrating odor information over time. Because arthropods share many homologous brain structures—antennal lobes for processing olfactory information, mechanosensors for processing flow, mushroom bodies (or hemi-ellipsoid bodies) for associative learning, and central complexes for navigation, it is likely that these closely related behaviors are mediated by conserved neural circuits. However, differences in the types of odors they seek, the physics of odor dispersal, and the physics of locomotion in water, air, and on substrates mean that these circuits must have adapted to generate a wide diversity of odor-seeking behaviors. In this review, we discuss common strategies and specializations observed in olfactory navigation behavior across arthropods, and review our current knowledge about the neural circuits subserving this behavior. We propose that a comparative study of arthropod nervous systems may provide insight into how a set of basic circuit structures has diversified to generate behavior adapted to different environments.

During the COVID-19 pandemic, the Stanford Summer Research Program - Amgen Scholars Program (SSRP) adapted to a remote program experience, gaining insights into maintaining inclusivity, access, and equity for its student participants. This paper outlines the transformative changes implemented by SSRP program staff and offers recommendations to promote equity while returning to in-person summer research programs, incorporating lessons learned in the COVID-19 era to center minoritized students.

Signaling via the B-cell receptor (BCR) is a key driver and therapeutic target in chronic lymphocytic leukemia (CLL). BCR stimulation of CLL cells induces expression of eIF4A, an initiation factor important for translation of multiple oncoproteins, and reduces expression of PDCD4, a natural inhibitor of eIF4A, suggesting that eIF4A may be a critical nexus controlling protein expression downstream of the BCR in these cells. We, therefore, investigated the effect of eIF4A inhibitors (eIF4Ai) on BCR-induced responses. We demonstrated that eIF4Ai (silvestrol and rocaglamide A) reduced anti-IgM-induced global mRNA translation in CLL cells and also inhibited accumulation of MYC and MCL1, key drivers of proliferation and survival, respectively, without effects on upstream signaling responses (ERK1/2 and AKT phosphorylation). Analysis of normal naïve and non-switched memory B cells, likely counterparts of the two main subsets of CLL, demonstrated that basal RNA translation was higher in memory B cells, but was similarly increased and susceptible to eIF4Ai-mediated inhibition in both. We probed the fate of MYC mRNA in eIF4Ai-treated CLL cells and found that eIF4Ai caused a profound accumulation of MYC mRNA in anti-IgM treated cells. This was mediated by MYC mRNA stabilization and was not observed for MCL1 mRNA. Following drug wash-out, MYC mRNA levels declined but without substantial MYC protein accumulation, indicating that stabilized MYC mRNA remained blocked from translation. In conclusion, BCR-induced regulation of eIF4A may be a critical signal-dependent nexus for therapeutic attack in CLL and other B-cell malignancies, especially those dependent on MYC and/or MCL1.

Carbene-based macromolecules are an emerging new stimuli-sensitive class of biomaterials that avoid the impediments of free radical polymerization but maintain a rapid liquid-to-biorubber transition. Activation of diazirine-grafted polycaprolactone polyol (CaproGlu) is limited to UVA wavelengths that have tissue exposure constraints and limited light intensities. For the first time, UVA is circumvented with visible light-emitting diodes at 445 nm (blue) to rapidly activate diazirine-to-carbene covalent cross-linking. Iridium photocatalysts serve to initiate diazirine, despite having little to no absorption at 445 nm. CaproGlu's liquid organic matrix dissolves the photocatalyst with no solvents required, creating a light transparent matrix. Considerable differences in cross-linking chemistry are observed in UVA vs visible/photocatalyst formulations. Empirical analysis and theoretical calculations reveal a more efficient conversion of diazirine directly to carbene with no diazoalkane intermediate detected. Photorheometry results demonstrate a correlation between shear moduli, joules light dose, and the lower limits of photocatalyst concentration required for the liquid-to-biorubber transition. Adhesion strength on ex vivo hydrated tissues exceeds that of cyanoacrylates, with a fixation strength of up to 20 kg·f·cm2. Preliminary toxicity assessment on leachates and materials directly in contact with mammalian fibroblast cells displays no signs of fibroblast cytotoxicity. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) Nanyang Technological University Accepted version T.W.J.S. and I.D. are co-inventors of patent application Hygroscopic, Crosslinking Coatings and Bioadhesives; PCT/ SG2018/050452. The project was supported by the Ministry of Education Tier 1 Grant RG17/18 (S): Novel light activated, diazo protecting groups; Ministry of Education Tier 2 Grant (MOE2018-T2-2-114): CaproGlu, double-sided wet tissue adhesives; NTUitive POC (Gap) Fund NGF/2018/05: Aesthetic Applications of CaproGlu Bioadhesives; and A*Star IAF PP Grant (H19/01/a0/0II9): CathoGlu Bioadhesives-preventing catheter extravasation and skin infections. L.B. acknowledges funding from the Spanish Ministry of Science and Innovation (MCIU), project PID2019- 104654GB-I00.

The current study compared postprandial glycemic and insulinemic responses to four nutrition bars containing two different doses of resistant starch type-4. Normoglycemic adults (

Performing endovascular medical interventions safely and efficiently requires a diverse set of skills that need to be practised in dedicated training sessions. Here, we used multimodal magnetic resonance (MR) imaging to determine the structural and functional plasticity and core skills associated with skill acquisition. A training group learned to perform a simulator-based endovascular procedure, while a control group performed a simplified version of the task; multimodal MR images were acquired before and after training. Using a well-controlled interaction design, we found strong, multimodal evidence for the role of the intraparietal sulcus (IPS) in endovascular skill acquisition that is in line with previous work implicating the structure in simple visuo-motor and mental rotation tasks. Our results provide a unique window into the multimodal nature of rapid structural and functional plasticity of the human brain while learning a multifaceted and complex clinical skill. Further, our results provide a detailed description of the plasticity process associated with endovascular skill acquisition and highlight specific facets of skills that could enhance current medical pedagogy and be useful to explicitly target during clinical resident training.

In this article, we take stock of the institutional logics perspective and highlight opportunities for new scholarship. While we celebrate the growth and generativity of the literature on institutional logics, we also note that there has been a troubling tendency in recent work to use logics as analytical tools, feeding disquiet about reification and reductionism. Seeding a broader scholarly agenda that addresses such weaknesses in the literature, we highlight nascent efforts that aim to more systematically understand institutional logics as complex, dynamic phenomena in their own right. In doing so, we argue for more research that probes how logics cohere and endure by unpacking the role of values, the centrality of practice, and the governance dynamics of institutional logics and their orders. Furthermore, we encourage bridging the study of institutional logics with various literatures, including ethnomethodology, phenomenology, professions, elites, world society, and the old institutionalism, to enhance progress in these directions.