As self-employment and entrepreneurship become increasingly important in our modern economies, Simon C. Parker provides a timely, definitive and comprehensive overview of the field. In this book he ...brings together and assesses the large and disparate literature on these subjects and provides an up-to-date overview of new research findings. Key issues addressed include: the impact of ability, risk, personal characteristics and the macroeconomy on entrepreneurship; issues involved in raising finance for entrepreneurial ventures, with an emphasis on the market failures that can arise as a consequence of asymmetric information; the job creation performance of the self-employed; the growth, innovation and exit behaviour of new ventures and small firms; and the appropriate role for governments interested in promoting self-employment and entrepreneurship. This book will serve as an essential reference guide to researchers, students and teachers of entrepreneurship in economics, business and management and other related disciplines.
Entrepreneurship is an integral part of economic change and growth. Yet until recently it has been largely neglected by economists. In The Economics of Entrepreneurship, Simon C. Parker draws on ...theoretical insights and recent empirical findings to show how economics can contribute to our understanding of entrepreneurship. The book is based on an earlier work, The Economics of Self-employment and Entrepreneurship (Cambridge University Press, 2004), that has quickly become an essential reference for academics researching the economics of entrepreneurship. Written in a more accessible style, this book contains much that made this earlier work so successful and, in addition, includes improved pedagogical features and new material on the theory of the firm, spin-offs, nascent entrepreneurship, growth-enhancing knowledge spillovers and social entrepreneurship. It can be used both as a reference text for academics from a variety of disciplines and as a textbook for graduate students.
•This ESMO Clinical Practice Guideline provides key recommendations on the management of prostate cancer.•Authorship includes a multidisciplinary group of experts from different institutions and ...countries in Europe.•Key treatment recommendations are provided.•Recommendations have been updated in the light of new evidence.
ABSTRACT
The Coma cluster is the nearest massive ($M \gtrsim 10^{15}\, \mathrm{M_\odot }$) galaxy cluster, making it an excellent laboratory to probe the influence of the cluster environment on ...galaxy star formation. Here, we present a sample of 41 galaxies with disturbed morphologies consistent with ram pressure stripping. These galaxies are identified visually using high-quality, multiband imaging from the Canada–France–Hawaii telescope covering ${\sim}9\, \mathrm{deg^2}$ of the Coma cluster. These ‘stripping candidates’ are clear outliers in common quantitative morphological measures, such as concentration-asymmetry and Gini-M20, confirming their disturbed nature. Based on the orientations of observed asymmetries, as well as the galaxy positions in projected phase space, these candidates are consistent with galaxies being stripped shortly after infall on to the Coma cluster. Finally, the stripping candidates show enhanced star formation rates, both relative to ‘normal’ star-forming Coma galaxies and isolated galaxies in the field. Ram pressure is likely driving an enhancement in star formation during the stripping phase, prior to quenching. On the whole, ram pressure stripping appears to be ubiquitous across all regions of the Coma cluster.
A major rate-limiting step in developing more effective immunotherapies for GBM is our inadequate understanding of the cellular complexity and the molecular heterogeneity of immune infiltrates in ...gliomas. Here, we report an integrated analysis of 201,986 human glioma, immune, and other stromal cells at the single cell level. In doing so, we discover extensive spatial and molecular heterogeneity in immune infiltrates. We identify molecular signatures for nine distinct myeloid cell subtypes, of which five are independent prognostic indicators of glioma patient survival. Furthermore, we identify S100A4 as a regulator of immune suppressive T and myeloid cells in GBM and demonstrate that deleting S100a4 in non-cancer cells is sufficient to reprogram the immune landscape and significantly improve survival. This study provides insights into spatial, molecular, and functional heterogeneity of glioma and glioma-associated immune cells and demonstrates the utility of this dataset for discovering therapeutic targets for this poorly immunogenic cancer.
Diabetic nephropathy is characterized by damage to both the glomerulus and tubulointerstitium, but relatively little is known about accompanying cell-specific changes in gene expression. We performed ...unbiased single-nucleus RNA sequencing (snRNA-seq) on cryopreserved human diabetic kidney samples to generate 23,980 single-nucleus transcriptomes from 3 control and 3 early diabetic nephropathy samples. All major cell types of the kidney were represented in the final dataset. Side-by-side comparison demonstrated cell-type–specific changes in gene expression that are important for ion transport, angiogenesis, and immune cell activation. In particular, we show that the diabetic thick ascending limb, late distal convoluted tubule, and principal cells all adopt a gene expression signature consistent with increased potassium secretion, including alterations in Na⁺/K⁺-ATPase, WNK1, mineralocorticoid receptor, and NEDD4L expression, as well as decreased paracellular calcium and magnesium reabsorption. We also identify strong angiogenic signatures in glomerular cell types, proximal convoluted tubule, distal convoluted tubule, and principal cells. Taken together, these results suggest that increased potassium secretion and angiogenic signaling represent early kidney responses in human diabetic nephropathy.
The integration of single cell transcriptome and chromatin accessibility datasets enables a deeper understanding of cell heterogeneity. We performed single nucleus ATAC (snATAC-seq) and RNA ...(snRNA-seq) sequencing to generate paired, cell-type-specific chromatin accessibility and transcriptional profiles of the adult human kidney. We demonstrate that snATAC-seq is comparable to snRNA-seq in the assignment of cell identity and can further refine our understanding of functional heterogeneity in the nephron. The majority of differentially accessible chromatin regions are localized to promoters and a significant proportion are closely associated with differentially expressed genes. Cell-type-specific enrichment of transcription factor binding motifs implicates the activation of NF-κB that promotes VCAM1 expression and drives transition between a subpopulation of proximal tubule epithelial cells. Our multi-omics approach improves the ability to detect unique cell states within the kidney and redefines cellular heterogeneity in the proximal tubule and thick ascending limb.
Single-cell sequencing technologies have advanced our understanding of kidney biology and disease, but the loss of spatial information in these datasets hinders our interpretation of intercellular ...communication networks and regional gene expression patterns. New spatial transcriptomic sequencing platforms make it possible to measure the topography of gene expression at genome depth.
We optimized and validated a female bilateral ischemia-reperfusion injury model. Using the 10× Genomics Visium Spatial Gene Expression solution, we generated spatial maps of gene expression across the injury and repair time course, and applied two open-source computational tools, Giotto and SPOTlight, to increase resolution and measure cell-cell interaction dynamics.
An ischemia time of 34 minutes in a female murine model resulted in comparable injury to 22 minutes for males. We report a total of 16,856 unique genes mapped across our injury and repair time course. Giotto, a computational toolbox for spatial data analysis, enabled increased resolution mapping of genes and cell types. Using a seeded nonnegative matrix regression (SPOTlight) to deconvolute the dynamic landscape of cell-cell interactions, we found that injured proximal tubule cells were characterized by increasing macrophage and lymphocyte interactions even 6 weeks after injury, potentially reflecting the AKI to CKD transition.
In this transcriptomic atlas, we defined region-specific and injury-induced loss of differentiation markers and their re-expression during repair, as well as region-specific injury and repair transcriptional responses. Lastly, we created an interactive data visualization application for the scientific community to explore these results (http://humphreyslab.com/SingleCell/).
Giant cell tumor (GCT) of bone is a rare, benign, aggressive bone tumor with an unusual capacity to metastasize to the lung. It was the goal of this study to identify patient and treatment-specific ...variables associated with the development of pulmonary metastases of GCT of bone.
From 1980 to 2009, 291 patients with benign GCT of bone were treated at our institution, and 167 were followed for at least two years. Eleven (6.6%) of these 167 patients developed biopsy-confirmed pulmonary metastasis. All patients were evaluated relative to nine patient, disease, and treatment-specific variables.
We identified four properties of benign GCT of bone associated with an increased risk of metastasis on univariate analysis: age at diagnosis, axial location of the primary GCT, primary Enneking stage-3 disease, and local recurrence. Multivariate analysis showed local recurrence to be an independent risk factor for pulmonary metastasis (adjusted odds ratio, 7.42).
There is an increased risk of pulmonary metastasis of GCT of bone in patients who are younger, present with Enneking stage-3 disease, develop local recurrence, and/or present with axial disease. The mode of treatment was not found to be associated with the development of pulmonary metastasis.
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