The Palm measure and the Voronoi tessellation for the Ginibre process

We prove that the Palm measure of the Ginibre process is obtained by removing a Gaussian distributed point from the process and adding the origin. We obtain also precise formulas describing the law of the typical cell of Ginibre--Voronoi tessellation. We show that near the germs of the cells a more important part of the area is captured in the Ginibre--Voronoi tessellation than in the Poisson--Voronoi tessellation. Moment areas of corresponding subdomains of the cells are explicitly evaluated.Comment: Published in at http://dx.doi.org/10.1214/09-AAP620 the Annals of Applied Probability (http://www.imstat.org/aap/) by the Institute of Mathematical Statistics (http://www.imstat.org

Cardiac Resynchronization Therapy: Who Benefits?

Background: Cardiac resynchronization therapy (CRT) has been well established in multiple large trials to improve symptoms, hospitalizations, reverse remodeling, and mortality in well-selected patients with heart failure when used in addition to optimal medical therapy. Updated consensus guidelines outline patients in whom such therapy is most likely to result in substantial benefit. However, pooled data have demonstrated that only approximately 70% of patients who qualify for CRT based on current indications actually respond favorably. In addition, current guidelines are based on outcomes from the carefully selected patients enrolled in clinical trials, and almost certainly fail to include all patients who might benefit from CRT. Findings: The identification of patients most likely to benefit from CRT requires consideration of factors beyond these standard criteria, QRS morphology with particular consideration in patients with left bundle-branch block pattern, extent of QRS prolongation, etiology of cardiomyopathy, rhythm, and whether the patient requires or will eventually need antibradycardia pacing. In addition, the baseline severity of functional impairment may influence the type of benefit to be expected from CRT; for example, New York Heart Association class I patients may derive long-term benefit in cardiac structure and function, but no benefit in symptoms or hospitalizations can be reasonably expected. In contrast, certain New York Heart Association class IV patients may be too sick to realize long-term mortality benefits from CRT, but improvements in hemodynamic profile and functional capacity may represent vital advances in this population. Conclusion: This review evaluates the evidence regarding the various factors that can predict positive or even detrimental responses to CRT, to help better determine who benefits most from this evolving therapy

Gunshot wounds to the penis and scrotum : a narrative review of management in civilian and military settings

CITATION: Goldman, Charlotte et al. 2021. Gunshot wounds to the penis and scrotum : a narrative review of management in civilian and military settings. Translational Andrology and Urology, 10(6):2596-2608, doi:10.21037/tau-20-1175.The original publication is available at: https://pubmed.ncbi.nlm.nih.govENGLISH ABSTRACT: Gunshot wounds (GSW) to the penis and scrotum are present in two thirds of all genitourinary (GU) trauma, with a growing proportion of blast injuries in the military setting. Depending on the energy of the projectile, the injury patterns present differently for military and civilian GSWs. In this review, we sought to provide a detailed overview of GSWs to the external genitalia, from mechanisms to management. We examine how ballistic injury impacts tissues, as well as the types of injuries that occur, and how to assess these injuries to the external genitalia. If there is concern for injury to the deep structures of the penis or scrotum, operative exploration and repair is warranted. Relevant history and physical examination, role of imaging, and choice of conservative or surgical treatment options in the civilian and military setting are discussed, as well as guidelines for management set forth by the American Urological Association (AUA) and European Association of Urology (EAU).Publisher's versio

Lysosome-mediated processing of chromatin in senescence

Cellular senescence is a stable proliferation arrest, a potent tumor suppressor mechanism, and a likely contributor to tissue aging. Cellular senescence involves extensive cellular remodeling, including of chromatin structure. Autophagy and lysosomes are important for recycling of cellular constituents and cell remodeling. Here we show that an autophagy/lysosomal pathway processes chromatin in senescent cells. In senescent cells, lamin A/C–negative, but strongly γ-H2AX–positive and H3K27me3-positive, cytoplasmic chromatin fragments (CCFs) budded off nuclei, and this was associated with lamin B1 down-regulation and the loss of nuclear envelope integrity. In the cytoplasm, CCFs were targeted by the autophagy machinery. Senescent cells exhibited markers of lysosomal-mediated proteolytic processing of histones and were progressively depleted of total histone content in a lysosome-dependent manner. In vivo, depletion of histones correlated with nevus maturation, an established histopathologic parameter associated with proliferation arrest and clinical benignancy. We conclude that senescent cells process their chromatin via an autophagy/lysosomal pathway and that this might contribute to stability of senescence and tumor suppression

Protein profiling in hepatocellular carcinoma by label-free quantitative proteomics in two west african populations.

Background Hepatocellular Carcinoma is the third most common cause of cancer related death worldwide, often diagnosed by measuring serum AFP; a poor performance stand-alone biomarker. With the aim of improving on this, our study focuses on plasma proteins identified by Mass Spectrometry in order to investigate and validate differences seen in the respective proteomes of controls and subjects with LC and HCC. Methods Mass Spectrometry analysis using liquid chromatography electro spray ionization quadrupole time-of-flight was conducted on 339 subjects using a pooled expression profiling approach. ELISA assays were performed on four significantly differentially expressed proteins to validate their expression profiles in subjects from the Gambia and a pilot group from Nigeria. Results from this were collated for statistical multiplexing using logistic regression analysis. Results Twenty-six proteins were identified as differentially expressed between the three subject groups. Direct measurements of four; hemopexin, alpha-1-antitrypsin, apolipoprotein A1 and complement component 3 confirmed their change in abundance in LC and HCC versus control patients. These trends were independently replicated in the pilot validation subjects from Nigeria. The statistical multiplexing of these proteins demonstrated performance comparable to or greater than ALT in identifying liver cirrhosis or carcinogenesis. This exercise also proposed preliminary cut offs with achievable sensitivity, specificity and AUC statistics greater than reported AFP averages. Conclusions The validated changes of expression in these proteins have the potential for development into high-performance tests usable in the diagnosis and or monitoring of HCC and LC patients. The identification of sustained expression trends strengthens the suggestion of these four proteins as worthy candidates for further investigation in the context of liver disease. The statistical combinations also provide a novel inroad of analyses able to propose definitive cut-offs and combinations for evaluation of performance

A high-resolution map of human evolutionary constraint using 29 mammals.

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ∼4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ∼60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease

EVI1 activation in blast crisis CML due to juxtaposition to the rare 17q22 partner region as part of a 4-way variant translocation t(9;22)

<p>Abstract</p> <p>Background</p> <p>Variant translocations t(9;22) occur in 5 to 10% of newly diagnosed CMLs and additional genetic changes are present in 60–80% of patients in blast crisis (BC). Here, we report on a CML patient in blast crisis presenting with a four-way variant t(9;22) rearrangement involving the <it>EVI1 </it>locus.</p> <p>Methods</p> <p>Dual-colour Fluorescence In Situ Hybridisation was performed to unravel the different cytogenetic aberrations. Expression levels of <it>EVI1 </it>and <it>BCR/ABL1 </it>were investigated using real-time quantitative RT-PCR.</p> <p>Results</p> <p>In this paper we identified a patient with a complex 4-way t(3;9;17;22) which, in addition to <it>BCR/ABL1 </it>gene fusion, also resulted in <it>EVI1 </it>rearrangement and overexpression.</p> <p>Conclusion</p> <p>This report illustrates how a variant t(9;22) translocation can specifically target a second oncogene most likely contributing to the more aggressive phenotype of the disease. Molecular analysis of such variants is thus warranted to understand the phenotypic consequences and to open the way for combined molecular therapies in order to tackle the secondary oncogenic effect which is unresponsive to imatinib treatment.</p

Endoplasmic spreading requires coalescence of vimentin intermediate filaments at force-bearing adhesions

10.1091/mbc.E12-05-0377Molecular Biology of the Cell24121-30MBCE

Cancer Genome Sequencing and Its Implications for Personalized Cancer Vaccines

New DNA sequencing platforms have revolutionized human genome sequencing. The dramatic advances in genome sequencing technologies predict that the $1,000 genome will become a reality within the next few years. Applied to cancer, the availability of cancer genome sequences permits real-time decision-making with the potential to affect diagnosis, prognosis, and treatment, and has opened the door towards personalized medicine. A promising strategy is the identification of mutated tumor antigens, and the design of personalized cancer vaccines. Supporting this notion are preliminary analyses of the epitope landscape in breast cancer suggesting that individual tumors express significant numbers of novel antigens to the immune system that can be specifically targeted through cancer vaccines