Inert gas clearance from tissue by co-currently and counter-currently arranged microvessels

To elucidate the clearance of dissolved inert gas from tissues, we have developed numerical models of gas transport in a cylindrical block of tissue supplied by one or two capillaries. With two capillaries, attention is given to the effects of co-current and counter-current flow on tissue gas clearance. Clearance by counter-current flow is compared with clearance by a single capillary or by two co-currently arranged capillaries. Effects of the blood velocity, solubility, and diffusivity of the gas in the tissue are investigated using parameters with physiological values. It is found that under the conditions investigated, almost identical clearances are achieved by a single capillary as by a co-current pair when the total flow per tissue volume in each unit is the same (i.e., flow velocity in the single capillary is twice that in each co-current vessel). For both co-current and counter-current arrangements, approximate linear relations exist between the tissue gas clearance rate and tissue blood perfusion rate. However, the counter-current arrangement of capillaries results in less-efficient clearance of the inert gas from tissues. Furthermore, this difference in efficiency increases at higher blood flow rates. At a given blood flow, the simple conduction-capacitance model, which has been used to estimate tissue blood perfusion rate from inert gas clearance, underestimates gas clearance rates predicted by the numerical models for single vessel or for two vessels with co-current flow. This difference is accounted for in discussion, which also considers the choice of parameters and possible effects of microvascular architecture on the interpretation of tissue inert gas clearance

Prospectus, May 7, 1980

STAERKEL ANNOUNCES ADDITIONS, CHANGES TO TAKE PLACE BEFORE FALL; Inflation plan announced; Interest-gathering accounts: big financial changes for U.S.; Walsh, Wienke to be 1980-81 co-editors; Resolution is just a suggestion; Youngersters voicing opinions on candidates; Trikes: the new mode of transportation; Special Olympics teaches student; Spring fever in college; Krannert events are listed; Letters to the Editor; REO still favorite in the Midwest; Dates to live by; Movie tells of anti-war movement in \u2760s; Rec students provide overnight camp-out; The sky\u27s the limit; Classifieds; C-U \u27turned upside down\u27 by punch of Journey and Ramones; Training for women; Trackmen win Region, smash state records; Parkland bows out of Section, prepares for conference tourney; Cobras lose at State; Complete Parkland Statisticshttps://spark.parkland.edu/prospectus_1980/1027/thumbnail.jp

Endosialin (TEM1, CD248) is a marker of stromal fibroblasts and is not selectively expressed on tumour endothelium

AbstractFibroblasts are a diverse cell type and display clear topographic differentiation and positional memory. In a screen for fibroblast specific markers we have characterized four monoclonal antibodies to endosialin (TEM1/CD248). Previous studies have reported that endosialin is a tumour endothelium marker and is localized intracellularly. We demonstrate conclusively that endosialin is a cell surface glycoprotein and is predominantly expressed by fibroblasts and a subset of pericytes associated with tumour vessels but not by tumour endothelium. These novel antibodies will facilitate the isolation and classification of fibroblast and pericyte lineages as well as the further functional analysis of endosialin

Risk-adjusted CUSUM control charts for shared frailty survival models with application to hip replacement outcomes: a study using the NJR dataset

Background:  Continuous monitoring of surgical outcomes after joint replacement is needed to detect which brands’ components have a higher than expected failure rate and are therefore no longer recommended to be used in surgical practice. We developed a monitoring method based on cumulative sum (CUSUM) chart specifically for this application.  Methods:  Our method entails the use of the competing risks model with the Weibull and the Gompertz hazard functions adjusted for observed covariates to approximate the baseline time-to-revision and time-to-death distributions, respectively. The correlated shared frailty terms for competing risks, corresponding to the operating unit, are also included in the model. A bootstrap-based boundary adjustment is then required for risk-adjusted CUSUM charts to guarantee a given probability of the false alarm rates. We propose a method to evaluate the CUSUM scores and the adjusted boundary for a survival model with the shared frailty terms. We also introduce a unit performance quality score based on the posterior frailty distribution. This method is illustrated using the 2003-2012 hip replacement data from the UK National Joint Registry (NJR). Results:  We found that the best model included the shared frailty for revision but not for death. This means that the competing risks of revision and death are independent in NJR data. Our method was superior to the standard NJR methodology. For one of the two monitored components, it produced alarms four years before the increased failure rate came to the attention of the UK regulatory authorities. The hazard ratios of revision across the units varied from 0.38 to 2.28. Conclusions:  An earlier detection of failure signal by our method in comparison to the standard method used by the NJR may be explained by proper risk-adjustment and the ability to accommodate time-dependent hazards. The continuous monitoring of hip replacement outcomes should include risk adjustment at both the individual and unit level

Integrative analysis of neuroblastoma by single-cell RNA sequencing identifies the NECTIN2-TIGIT axis as a target for immunotherapy

Pediatric patients with high-risk neuroblastoma have poor survival rates and urgently need more effective treatment options with less side effects. Since novel and improved immunotherapies may fill this need, we dissect the immunoregulatory interactions in neuroblastoma by single-cell RNA-sequencing of 24 tumors (10 pre- and 14 post-chemotherapy, including 5 pairs) to identify strategies for optimizing immunotherapy efficacy. Neuroblastomas are infiltrated by natural killer (NK), T and B cells, and immunosuppressive myeloid populations. NK cells show reduced cytotoxicity and T cells have a dysfunctional profile. Interaction analysis reveals a vast immunoregulatory network and identifies NECTIN2-TIGIT as a crucial immune checkpoint. Combined blockade of TIGIT and PD-L1 significantly reduces neuroblastoma growth, with complete responses (CR) in vivo. Moreover, addition of TIGIT+PD-L1 blockade to standard relapse treatment in a chemotherapy-resistant Th-ALKF1174L/MYCN 129/SvJ syngeneic model induces CR. In conclusion, our integrative analysis provides promising targets and a rationale for immunotherapeutic combination strategies

Games People Play: The Collapse of “Masculinities” and the Rise of Masculinity as Spectacle

Perspective is important. When Andy Warhol produced an art piece of 13 police mugshots of “Thirteen Most Wanted Men” for the New York World’s Fair in 1964, the work was hurriedly painted over by concerned authorities before the public could view it. It was only years later that the Warhol’s subversive (homoerotic) gaze on the FBI list was more widely appreciated (Crimp in Social Text 59: 49–66, 1999; Siegel in Art Journal 62(1): 7–13, 2003). I begin with this story because it points to key issues I want to take up in this chapter, in particular, the importance of “audience” and different readings when it comes to masculinity. While current theory tends to locate masculinity in the actors, what if it is better located in the audience? What if masculinity was better understood as a kind of public spectacle? In addition, there are the naturally subversive elements of gender (e.g. think of drag performances); the game-like nature of masculinity (men might feel compelled to play along with expectations of masculinity—think of brutal playground expectations on boys—but it doesn’t mean they are not aware of its inauthenticity); and the inevitable—but less discussed link—with sexuality (see below)