Graphs of curves on infinite-type surfaces with mapping class group actions

We study when the mapping class group of an infinite-type surface $S$ admits an action with unbounded orbits on a connected graph whose vertices are simple closed curves on $S$. We introduce a topological invariant for infinite-type surfaces that determines in many cases whether there is such an action. This allows us to conclude that, as non-locally compact topological groups, many big mapping class groups have nontrivial coarse geometry in the sense of Rosendal.Comment: 25 pages, 5 figures. v3: Final version, incorporates referee's comments, to appear at Annales de l'Institut Fourie

Stable cubulations, bicombings, and barycenters

We prove that the hierarchical hulls of finite sets of points in mapping class groups and Teichm\"uller spaces are stably approximated by a CAT(0) cube complexes, strengthening a result of Behrstock-Hagen-Sisto. As applications, we prove that mapping class groups are semihyperbolic and Teichm\"uller spaces are coarsely equivariantly bicombable, and both admit stable coarse barycenters. Our results apply to the broader class of "colorable" hierarchically hyperbolic spaces and groups.Comment: 80 pages, 25 figure

Survey of equine veterinarians regarding primary equine back pain in the United States

Back pain is a common complaint, clinical finding and performance limiting factor in sport horses. This study sought to gather current veterinary trends in the diagnosis, treatment and management of primary equine back pain in the United States. A 22 question survey was distributed electronically to equine practitioners through AAEP and ACVSMR listservs and through closed social media groups. The survey was open from April 20, 2022 to July 5, 2022. Responses were analyzed using Microsoft excel pivot tables. Ninety-seven survey responses were obtained and analyzed. Respondents reported the clinical signs most frequently relayed to them by the owner/rider/trainer of horses diagnosed with primary back pain were behavioral issues and poor performance. Most common diagnostic tests reported were radiography of the spinous processes, thoraco-lumbar vertebral bodies, and transcutaneous ultrasound of the thoraco-lumbar region. Most common pathologies reported were impinging dorsal spinous processes, degenerative sacro-iliac joint disease, and osteoarthritis in lumbar or thoracic articular process joints. In regards to impinging spinous process (“kissing spine”) treatments, 72.2% of respondents recommended surgery only after non-surgical treatments failed, and 14.6% of respondents never recommended surgery. The majority (82%) of respondents reported some level of improvement in clinical signs of primary back pain with rehabilitation alone. To date, there has been no consensus or discussion about common abnormalities, diagnostic tests, treatments or management options for primary equine back pain in the United States. Results of this survey are a starting point showing current trends in diagnosis, treatment and management of primary equine back pain among equine practitioners in the United States showing 82% of practitioners using rehabilitation as a component of treatment

T-Cell Infiltration and Adaptive Treg Resistance in Response to Androgen Deprivation With or Without Vaccination in Localized Prostate Cancer

Purpose: Previous studies suggest that androgen deprivation therapy (ADT) promotes antitumor immunity in prostate cancer. Whether a vaccine-based approach can augment this effect remains unknown. Experimental Design: Therefore, we conducted a neoadjuvant, randomized study to quantify the immunologic effects of a granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting allogeneic cellular vaccine in combination with low-dose cyclophosphamide (Cy/GVAX) followed by degarelix versus degarelix alone in patients with high-risk localized prostate adenocarcinoma who were planned for radical prostatectomy. Results: Both Cy/GVAX plus degarelix and degarelix alone led to significant increases in intratumoral CD8+ T cell infiltration and PD-L1 expression as compared to a cohort of untreated, matched controls. However, the CD8+ T cell infiltrate was accompanied by a proportional increase in regulatory T cells (Treg), suggesting that adaptive Treg resistance may dampen the immunogenicity of ADT. Although Cy/GVAX followed by degarelix was associated with a modest improvement in time-to-PSA progression and time-to-next treatment as well as an increase in PD-L1, there was no difference in the CD8 T-cell infiltrate as compared to degarelix alone. Gene expression profiling demonstrated that CHIT1, a macrophage marker, was differentially upregulated with Cy/GVAX plus degarelix compared to degarelix alone. Conclusions: Our results highlight that ADT with or without Cy/GVAX induces a complex immune response within the prostate tumor microenvironment. These data have important implications for combining ADT with immunotherapy. In particular, our finding that ADT increases both CD8+ T cells and Tregs, supports the development of regimens combining ADT with Treg-depleting agents in the treatment of prostate cancer

Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.

Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery