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Introduction: Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults and can be primary or secondary. The antigenic target of antibodies in 70% of primary cases is phospholipase A2 receptor (PLA2R). The presence or absence of mesangial electron-dense deposits has been used to distinguish between primary and secondary MN. Mesangial deposits suggest MN due to lupus, infection, or other causes, though they are reported to occur in approximately 10% of primary MN. Staining for PLA2R is now frequently used for confirming a diagnosis of primary MN. If mesangial deposits predict a secondary cause, they should be more frequent in PLA2R-negative biopsies. Methods: A review of institutional kidney biopsies between March 2017 and June 2020 identified all cases of MN. Cases with a diagnosis of lupus or near “full-house” staining by immunofluorescence microscopy (IF) were excluded. Light microscopy, IF, and electron microscopy (EM) were performed. PLA2R staining was performed by IF. EM for all cases was reviewed and electron-dense deposit location, distribution, and size were determined. Results: Ninety-three cases of MN were identified, of which 86 had both PLA2R staining and EM performed. Of these, 51 cases (59%) were positive for PLA2R and 35 (41%) were negative. Mesangial electron-dense deposits were present in 22 (25.6%) of the 86 cases, including 27.5% (14/51) of PLA2R-positive cases and 22.8% (8/35) of PLA2R-negative cases. No difference was seen in size or distribution of deposits, or other features considered suggestive of secondary MN. Conclusion: PLA2R-negative cases were not more likely to have mesangial deposits than PLA2R-positive cases. Mesangial deposits should not be used as an indicator of secondary MN.

We challenge Knight’s century-old classic model of entrepreneurship by arguing hypotheses that he was wrong not only about the relationship between uncertainty and entrepreneurial performance but a...

It has been recognized that T cells have a pathogenic role in anti-neutrophil cytoplasmic antibody- (ANCA) associated vasculitis, in addition to being dominant cells in the interstitium in ANCA glomerulonephritis (GN). Given there are differences in renal outcomes based on ANCA type, we sought to characterize the interstitial infiltrate in ANCA GN to determine differences in relation to ANCA type and renal function. Immunohistochemistry stains for CD3, CD4, CD20, C4d and FOXP3 were done in renal biopsies of patients with ANCA GN. Light microscopy was used to determine the percentage of cortical interstitium containing positive cells. Demographics, ANCA type and entry eGFR were recorded. The level of staining was compared between ANCA type and entry eGFR using Wilcoxon rank-sum test. Renal biopsies of 16 patients with MPO and 14 with PR3 ANCA GN were studied. CD3 cells were the predominant cells, with all biopsies staining positive for CD4 and FOXP3. C4d staining was negative in all biopsies, with no significant difference in staining between MPO and PR3 groups for any of the identified cell types. However, regardless of ANCA type, FOXP3 staining was significantly higher in patients with baseline GFR 10 mL/min/1.73 m2(mean 7.54, SD 6.6 versus mean 2.67, SD 3.6; p = 0.04). These data confirm the role of T cells in ANCA GN and demonstrate no differences in interstitial T and B cell infiltrates between PR3 and MPO ANCA GN. Higher FOXP3 signal associates with lower renal function, suggesting a role for regulatory T cells. Further characterization of this T cell subset should be explored in future studies.

Objectives Indocyanine green (ICG) is a fluorescent dye which was initially used for liver functional assessment. Moreover, it is of value for intraoperative visualization of liver segments and bile ducts or primary and secondary liver tumors. Especially in minimally invasive liver surgery, this is essential to enhance the precision of anatomical guided surgery and oncological quality. As early adopters of ICG implementation into laparoscopic and robotic-assisted liver surgery in Germany, we summarize the current recommendations and share our experiences. Methods Actual strategies for ICG application in minimally invasive liver surgery were evaluated and summarized during a review of the literature. Experiences in patients who underwent laparoscopic or robotic-assisted liver surgery with intraoperative ICG staining between 2018 and 2020 from the Magdeburg registry for minimally invasive liver surgery (MD-MILS) were evaluated and the data were analyzed retrospectively. Results ICG can be used to identify anatomical liver segments by fluorescence angiography via direct or indirect tissue staining. Fluorescence cholangiography visualizes the intra- and extrahepatic bile ducts. Primary and secondary liver tumors can be identified with a sensitivity of 69–100%. For this 0.5 mg/kg body weight ICG must be applicated intravenously 2–14 days prior to surgery. Within the MD-MILS we identified 18 patients which received ICG for intraoperative tumor staining of hepatocellular carcinoma (HCC), cholangiocarcinoma, peritoneal HCC metastases, adenoma, or colorectal liver metastases. The sensitivity for tumor staining was 100%. In 27.8% additional liver tumors were identified by ICG fluorescence. In 39% a false positive signal could be detected. This occurred mainly in cirrhotic livers. Conclusions ICG staining is a simple and useful tool to assess individual hepatic anatomy or to detect tumors during minimally invasive liver surgery. It may enhance surgical precision and improve oncological quality. False-positive detection rates of liver tumors can be reduced by respecting the tumor entity and liver functional impairments.

Kidney involvement is common in patients with systemic lupus erythematosus (SLE). This study investigates the clinical and prognostic characteristics of thrombotic microangiopathy (TMA) compared to class IV lupus nephritis in SLE patients. A retrospective review of patients who underwent kidney biopsy, with a primary diagnosis of SLE and TMA between June 2006 and September 2018 was conducted. Those patients were subsequently compared to patients with class IV lupus nephritis between January 2018 and December 2018. Demographics, laboratory, and serological data at the time of biopsy were abstracted. Among 214 SLE patients records screened, 27 were included in the final analysis. Eight patients had lupus-related TMA without evidence of active lupus nephritis, while 19 patients had class IV lupus nephritis without evidence of TMA. TMA patients had significantly higher lactate dehydrogenase levels (718 ± 499 vs. 264 ± 107.7 U/L, p = 0.009), serum C3 (100.6 ± 39.3 vs. 65.8 ± 27 mg/dL, p = 0.049), white blood cell count (14743.8 ± 7933.3 vs. 5807.9 ± 2053.2 × 10E3/uL, p

We discuss the impediments to theorizing about entrepreneurial activity, why these exist, and what to do about them. We do so because we believe that the evolution of theory in entrepreneurship has been frustratingly slow. We approach the relevant issues from an appropriate but narrow perspective—through the analysis of two pairs of recent articles published in the generalist top theory outlet—the Academy of Management Review. We consider these as exemplars of high-quality, high-visibility, likely-to-be-highly-cited, and new entrepreneurship theorizing. All four articles focus on original partial theory-building in the entrepreneurial process. These articles address different challenges facing different individual entrepreneurs, with many similarities in approach. However, each work argues its new propositions or insights from a non-entrepreneurial reference theory, which may well be one of the sacrifices that must be made to get published in top mainstream journals. We focus on the similarities of these articles to argue our points about why theorizing in our field is unlikely to improve in the near future and to identify the main impediments to such improvements. We explore the negative implications for our field’s future, and then we suggest five bold steps to better the prognostication.

Introduction In patients with systemic lupus erythematosus (SLE) without concurrent active urinary sediment or unexplained acute kidney injury (AKI), current guidelines recommend performing a kidney biopsy in those with at least 500 mg/24-hour (European League Against Rheumatism/European Renal Association-European Dialysis and Transplant Association [EULAR/ERA-EDTA]) or 1000 mg/24-hour (American College of Rheumatology [ACR]) proteinuria. To evaluate the relevance of these indications, we studied histopathologic findings in patients with SLE with proteinuria below these cutoffs. Methods We retrospectively reviewed the clinical, laboratory and histological characteristics of patients with SLE with, Graphical abstract

The existence of ambiguity presents a challenge to decision-makers as it eliminates the ability to apply standard optimization approaches, such as those based on calculating the objective expected values of alternative actions. In reality, ambiguity arises in most strategically important decisions in some form because of the genuine limits on the decision-maker’s rationality and on the information available about the alternatives and the future. To address that reality, we define such problems as strategic decision-making under ambiguity where choices over resource investments must be made in competitive environments where possible outcomes and their payoffs are known ex ante, but the probabilities of such outcomes are unknowable ex ante. We outline a multi-step, logical approach for addressing such problems in theory with the goal of providing an improved basis for practical decisions that should increase organizational performance.

We complement emerging theory-building in social entrepreneurship by adopting a new perspective. We start with the assumption that the existence of opposing interests is the main reason that things...

Acute kidney injury (AKI) due to cisplatin is a significant problem that limits its use as an effective chemotherapeutic agent. T cell receptor+CD4−CD8− double negative (DN) T cells constitute the major T cell population in the human and mouse kidney, express programmed cell death protein (PD)-1, and protect from ischemic AKI. However, the pathophysiological roles of DN T cells in cisplatin-induced AKI is unknown. In this study, wild-type mice were treated with cisplatin (30 mg/kg) or vehicle, and the effects on kidney DN T cell numbers and function were measured. In vitro experiments evaluated effects of kidney DN T cells on cisplatin-induced apoptosis and PD ligand 1 (PD-L1) in renal epithelial cells. Adoptive transfer experiments assessed the therapeutic potential of DN T cells during cisplatin-induced AKI. Our results show that kidney DN T cell population increased at 24 h and declined by 72 h after cisplatin treatment. Cisplatin treatment increased kidney DN T cell proliferation, apoptosis, CD69, and IL-10 expression, whereas CD62L, CD44, IL-17A, interferon-γ, and TNF-α were downregulated. Cisplatin treatment decreased both PD-1 and natural killer 1.1 subsets of kidney DN T cells with a pronounced effect on the PD-1 subset. In vitro kidney DN T cell coculture decreased cisplatin-induced apoptosis in kidney proximal tubular epithelial cells, increased Bcl-2, and decreased cleaved caspase 3 expression. Cisplatin-induced expression of PD ligand 1 was reduced in proximal tubular epithelial cells cocultured with DN T cells. Adoptive transfer of DN T cells attenuated kidney dysfunction and structural damage from cisplatin-induced AKI. These results demonstrate that kidney DN T cells respond rapidly and play a protective role during cisplatin-induced AKI.

We propose a partial theory explaining the processing of opportunities by individuals in organizations, specifically for opportunities with both commercial and moral significance (measured as intensities). The goal of such theorizing is to identify and analyze the range of interactions that the ethical and economic impacts of an opportunity can have so that managers can make better decisions on their exploitation and modification. We explain why and how there is variance in the processing of the ideas behind such opportunities as caused by their moral and commercial intensities. We explain the likely interactions between those two intensities, and when they occur and what can result. Doing so complements work in social entrepreneurship and corporate social responsibility by filling the gaps of the possible combinations of economic and ethical interactions. We provide these explanations by leveraging a precedent model that had adapted a standard knowledge-processing method to ethical decision-making issues. The explanations resonate because our model leverages the traditional textbook entrepreneurship opportunity evaluation criteria to provide a holistic view of an underlying idea’s commercial intensity, a view that aligns with the driving assumption that the focal decision-makers are boundedly rational.

Hypertensive patients are frequently treated with inhibitors of the renin-angiotensin system (RASi). In renin knockout mice, cells programmed for the renin phenotype ( Renin null cells) stimulate the concentric hypertrophy of intrarenal arteries and arterioles. The Renin null cells invade the arteriolar walls and stimulate the concentric growth of smooth muscle cells (SMCs). EM exam showed disorganized glomerular arterioles, marked layering of SMCs and increased basement membrane, compared to a single organized SMC layer in WT mice. The hypertrophy leads to flow obstruction, ischemia, and renal failure.We hypothesize that Renin null cells or renin-expressing cells from animals treated with RASi possess a unique transcriptome that drives their own abnormal fate and the concentric accumulation of SMCs.To test this, we performed single-cell RNA-seq in WT and Renin null cells. We also tested genetically hypertensive mice and their normotensive controls treated with captopril for 6 months. Further, we examined renal biopsies from patients treated with RAS inhibitors for more than 5 years, age-matched controls without RAS inhibitors, and healthy control kidneys.The transcriptional profile of Renin null cells was markedly different from the profile of WT cells. Gene ontology indicated that Renin null cells possess a contractile rather than the endocrine phenotype of WT cells ( p P P P 2 , without RAS; 677.8 ± 313.4 μm 2 , vs. long-term RAS; 1347 ± 529.9 μm 2 , P =0.003).In conclusion, renin cells stimulated by inhibition of RAS have specific molecular programs that contribute to arterial disease.

Inhibitors of the renin-angiotensin system (RAS) are widely used to treat hypertension. Using mice harboring fluorescent cell lineage tracers, single-cell RNA-Seq, and long-term inhibition of RAS in both mice and humans, we found that deletion of renin or inhibition of the RAS leads to concentric thickening of the intrarenal arteries and arterioles. This severe disease was caused by the multiclonal expansion and transformation of renin cells from a classical endocrine phenotype to a matrix-secretory phenotype: the cells surrounded the vessel walls and induced the accumulation of adjacent smooth muscle cells and extracellular matrix, resulting in blood flow obstruction, focal ischemia, and fibrosis. Ablation of the renin cells via conditional deletion of β1 integrin prevented arteriolar hypertrophy, indicating that renin cells are responsible for vascular disease. Given these findings, prospective morphological studies in humans are necessary to determine the extent of renal vascular damage caused by the widespread use of inhibitors of the RAS.

The field of social entrepreneurship has taken off with the explosive growth of different versions of the phenomena, like micro-credit, and with greater support, as from Ashoka and the Gates Founda...

Summary: It may be surprising that one of the most popular compensation schemes in business is so open to being hacked – to having managers cheat to win. We explore tournament theory to detail its vulnerabilities to various forms of cheating unilateral and multilateral. We identify who is most likely to be involved and under what conditions. We describe the costs to the victims, to the firm, and to society. We outline the possible strategic effects – in terms of firm performance. And, we discuss possible ways to address these vulnerabilities to the schemes we rely on to motivate managers to put in the right efforts, to take the right risks, and to lead the right way. JEL classification: M52, J33, D82, J31, D73, Keywords: Cheating, Managerial compensation schemes, Tournament theory, Vulnerabilities

We seek to fill a gap in the understanding of pre-entrepreneurial education. We use a field study to flesh out initial prescriptions on how to build successful high school entrepreneurship education programs. We draw from the applicable studies and related theoretical frameworks to highlight drivers of success. We conclude that the kind of heterogeneity in embodied in the ‘pre-entrepreneur’ high school students needs to be addressed better in our educational systems and our other societal support systems, that our educational systems need to recognize that people not only ‘think differently’ as entrepreneurs but also at different points in their lives, and that points to a need for innovation in business schools, especially in entrepreneurship education, to leverage what potential that the new high school models build. Thus, we propose that programs that leverage identifiable and meaningful heterogeneity in their students, expectations, and communities will experience greater success across many measures of value creation.

Purpose Assuming that supplier knowledge can either strengthen the partnership by nurturing the commitment and trust between partners or allow the buyer to be more calculative, this study aims to propose two types of knowledge sharing in supplier relationship – a type benefiting the partnership and another privately benefiting only one partner. Design/methodology/approach Using structural equation modeling and a surveyed dataset from 352 buyer–supplier partnerships, this study tested the research model of dual mechanism, where two types of knowledge sharing co-exist and have opposite effects on partnership longevity. Findings This study found that the two types of knowledge sharing create divergent effects on partnership continuation. For a buyer firm developing supplier knowledge, its supplier firm reciprocates by sharing knowledge with the buyer. While relation-specific knowledge promotes partnership longevity through developing trust, institutionalized knowledge hampers partnership longevity. Research limitations/implications Findings overall indicate that knowledge plays a more instrumental role in sharing knowledge in a buyer–supplier relationship, and alternative forces simultaneously work in the partnership. Although this study explicates two mediating mechanisms for the effect of supplier knowledge, there remain many unknown aspects of the effect. Practical implications From the buyer’s perspective, it is possible its institutionalized knowledge can facilitate its relationship with a current supply chain partner so that it can gain more benefits from the relationship. From the supplier’s perspective, caution should be exercised in selecting the type of knowledge to share. Social implications This study may have a broad impact on public policy by theorizing and testing why some partnerships last longer/shorter than others in association with the dynamics of the relationship initiated by one’s relational knowledge and the other’s knowledge sharing. Originality/value What this study contributes to involves the theorizing and testing the effects of the dual mechanism of knowledge sharing on partnership longevity. This study provides an example of a private investment in knowledge that is reciprocated with each type of knowledge – benefiting the partner and also benefiting the focal buyer firm.

Plastic deformation of samples compressed to Mbar pressures at high strain rates at the National Ignition Facility (NIF) forms the basis of ongoing material strength experiments in conditions relevant to meteor impacts, geophysics, armor development, and inertial confinement fusion. Hard x-ray radiography is the primary means of measuring the evolution of these samples, typically employing a slit-collimated high-Z microdot driven by the NIF laser to generate [Formula: see text] keV x rays [E. Gumbrell et al., Rev. Sci. Instrum. 89, 10G118 (2018) and C. M. Huntington et al., Rev. Sci. Instrum. 89, 10G121 (2018)]. Alternatively, a dysprosium “micro-flag” target driven by the Advanced Radiographic Capability laser ([Formula: see text] kJ, 10 ps) can deliver significantly higher spatiotemporal resolution [M. P. Hill et al., Rev. Sci. Instrum. 92, 033535 (2021)], especially in high-opacity samples. Initial experiments revealed problematic brightness and spectral gradients from this source, but by radiographing a set of diamond-turned, 105 µm-thick Pb test objects and supported by simulations using the 3D Monte Carlo code GEANT4, these geometry-dependent gradients across the field of view are quantified and mitigation strategies are assessed. In addition to significantly enhancing the modulation transfer function compared to the existing system, image stacking from multiple layers of image plate is shown to almost double the signal to noise ratio that will reduce uncertainties in future dynamic strength experiments.