Reflections on the Death Scene

An introduction to the Death Scene issue of Cultural Studies Review, with reflections on the nature of the death scene in general and on the specific issues covered by contributors

Cocaine-Induced Behavioral Sensitization: Effects of Haloperidol and SCH 23390 Treatments

An article by Bruce Mattingly published in the Fall of 1996 issue of the Pharmacology Biochemistry and Behavior Journal, pages 481-486

Chimeric antigen receptor–T cell therapy manufacturing: modelling the effect of offshore production on aggregate cost of goods

Cell and gene therapies have demonstrated excellent clinical results across a range of indications with chimeric antigen receptor (CAR)–T cell therapies among the first to reach market. Although these therapies are currently manufactured using patient-derived cells, therapies using healthy donor cells are in development, potentially offering avenues toward process improvement and patient access. An allogeneic model could significantly reduce aggregate cost of goods (COGs), potentially improving market penetration of these life-saving treatments. Furthermore, the shift toward offshore production may help reduce manufacturing costs. In this article, we examine production costs of an allogeneic CAR-T cell process and the potential differential manufacturing costs between regions. Two offshore locations are compared with regions within the United States. The critical findings of this article identify the COGs challenges facing manufacturing of allogeneic CAR-T immunotherapies, how these may evolve as production is sent offshore and the wider implication this trend could have

Application and Analysis of Bounded-Impulse Trajectory Models with Analytic Gradients

In the companion paper, analytic methods were presented for computing the Jacobian entries for two-sided direct shooting trajectory models that utilize the bounded-impulse approximation. In this paper we discuss practical implementation considerations. Efficient computation of the mathematical components required to compute the partials is discussed and a guiding numerical example is provided for validation purposes. A solar electric power model suitable for preliminary mission design is presented, including a method for handling thruster cut-off events that result in non-smooth derivatives. The challenges associated with incorporating the SPICE ephemeris system into an optimization framework are discussed and an alternative is presented that results in smooth time partials. Application problems illustrate the benefits of employing analytic Jacobian calculations vs. using the method of finite differences. The importance of accurately modeling hardware and operational constraints at the preliminary design stage, and the benefits of using an analytic Jacobian in a solver that combines the monotonic basin hopping heuristic method with a local gradient search are also explored

A Prospective Controlled Trial of an Electronic Hand Hygiene Reminder System

Background. The use of electronic hand hygiene reminder systems has been proposed as an approach to improve hand hygiene compliance among healthcare workers, although information on efficacy is limited. We prospectively assessed whether hand hygiene activities among healthcare workers could be increased using an electronic hand hygiene monitoring and reminder system. Methods. A prospective controlled clinical trial was conducted in 2 medical intensive care units (ICUs) at an academic medical center with comparable patient populations, healthcare staff, and physical layout. Hand hygiene activity was monitored concurrently in both ICUs, and the reminder system was installed in the test ICU. The reminder system was tested during 3 administered phases including: room entry/exit chimes, display of real-time hand hygiene activity, and a combination of the 2. Results. In the test ICU, the mean number of hand hygiene events increased from 1538 per day at baseline to 1911 per day (24% increase) with the use of a combination of room entry/exit chimes, real-time displays of hand hygiene activity, and manager reports (P \u3c .001); in addition, the ratio of hand hygiene to room entry/exit events also increased from 26.1% to 36.6% (40% increase, P \u3c .001). The performance returned to baseline (1473 hand hygiene events per day) during the follow-up phase. There was no significant change in hand hygiene activity in the control ICU during the course of the trial. Conclusions. In an ICU setting, an electronic hand hygiene reminder system that provided real-time feedback on overall unit-wide hand hygiene performance significantly increased hand hygiene activity

Analytic Gradient Computation for Bounded-Impulse Trajectory Models Using Two-Sided Shooting

Many optimization methods require accurate partial derivative information in order to ensure efficient, robust, and accurate convergence. This work outlines analytic methods for computing the problem Jacobian for two different bounded-impulse spacecraft trajectory models solved using two-sided shooting. The specific two-body Keplerian propagation method used by both of these models is described. Methods for incorporating realistic operational constraints and hardware models at the preliminary stage of a trajectory design effort are also demonstrated and the analytic methods derived are tested for accuracy using automatic differentiation. A companion paper will solve several relevant problems that show the utility of employing analytic derivatives, i.e. compared to using derivatives found using finite differences

Numerical Computation of a Continuous-thrust State Transition Matrix Incorporating Accurate Hardware and Ephemeris Models

A significant body of work exists showing that providing a nonlinear programming (NLP) solver with expressions for the problem constraint gradient substantially increases the speed of program execution and can also improve the robustness of convergence, especially for local optimizers. Calculation of these derivatives is often accomplished through the computation of spacecraft's state transition matrix (STM). If the two-body gravitational model is employed as is often done in the context of preliminary design, closed form expressions for these derivatives may be provided. If a high fidelity dynamics model, that might include perturbing forces such as the gravitational effect from multiple third bodies and solar radiation pressure is used then these STM's must be computed numerically. We present a method for the power hardward model and a full ephemeris model. An adaptive-step embedded eight order Dormand-Prince numerical integrator is discussed and a method for the computation of the time of flight derivatives in this framework is presented. The use of these numerically calculated derivatieves offer a substantial improvement over finite differencing in the context of a global optimizer. Specifically the inclusion of these STM's into the low thrust missiondesign tool chain in use at NASA Goddard Spaceflight Center allows for an increased preliminary mission design cadence

Bezlotoxumab for prevention of recurrent Clostridium difficile infection in patients at increased risk for recurrence

Background: Bezlotoxumab is a human monoclonal antibody against Clostridium difficile toxin B indicated to prevent C. difficile infection (CDI) recurrence (rCDI) in adults at high risk for rCDI. This post hoc analysis of pooled monocolonal antibodies for C.difficile therapy (MODIFY) I/II data assessed bezlotoxumab efficacy in participants with characteristics associated with increased risk for rCDI. Methods: The analysis population was the modified intent-to-treat population who received bezlotoxumab or placebo (n = 1554) by risk factors for rCDI that were prespecified in the statistical analysis plan: age ≥65 years, history of CDI, compromised immunity, severe CDI, and ribotype 027/078/244. The proportion of participants with rCDI in 12 weeks, fecal microbiota transplant procedures, 30-day all cause and CDI-associated hospital readmissions, and mortality at 30 and 90 days after randomization were presented. Results: The majority of enrolled participants (75.6%) had ≥1 risk factor; these participants were older and a higher proportion had comorbidities compared with participants with no risk factors. The proportion of placebo participants who experienced rCDI exceeded 30% for each risk factor compared with 20.9% among those without a risk factor, and the rCDI rate increased with the number of risk factors (1 risk factor: 31.3%; ≥3 risk factors: 46.1%). Bezlotoxumab reduced rCDI, fecal microbiota transplants, and CDI-associated 30-day readmissions in participants with risk factors for rCDI. Conclusions: The risk factors prespecified in the MODIFY statistical analysis plan are appropriate to identify patients at high risk for rCDI. While participants with ≥3 risk factors had the greatest reduction of rCDI with bezlotoxumab, those with 1 or 2 risk factors may also benefit. Clinical Trials Registration: NCT01241552 (MODIFY I) and NCT01513239 (MODIFY II)