In this study, we experimentally measure the frequency-dependent interactions between a gefitinib-resistant non–small cell lung cancer population and its sensitive ancestor via the evolutionary game assay. We show that cost of resistance is insufficient to accurately predict competitive exclusion and that frequency-dependent growth rate measurements are required. Using frequency-dependent growth rate data, we then show that gefitinib treatment results in competitive exclusion of the ancestor, while the absence of treatment results in a likely, but not guaranteed, exclusion of the resistant strain. Then, using simulations, we demonstrate that incorporating ecological growth effects can influence the predicted extinction time. In addition, we show that higher drug concentrations may not lead to the optimal reduction in tumor burden. Together, these results highlight the potential importance of frequency-dependent growth rate data for understanding competing populations, both in the laboratory and as we translate adaptive therapy regimens to the clinic.
DISCLAIMER: This article does not represent the official recommendation of the Cleveland Clinic or CaseWestern Reserve University School of Medicine, nor has it yet been peer reviewed. We are releasing it early, pre-peer review, to allow for quick dissemination/vetting by the scientific/clinical community given the necessity for rapid conservation of personal protective equipment (PPE) during this dire global situation. We welcome feedback from the community.Personal protective equipment (PPE), including face shields, surgical masks, and N95 respirators, is crucially important to the safety of both patients and medical personnel, particularly in the event of an infectious pandemic. As the incidence of Coronavirus Disease (COVID-19) increases exponentially in the United States and worldwide, healthcare provider demand for these necessities is currently outpacing supply. As such, strategies to extend the lifespan of the supply of medical equipment as safely as possible are critically important. In the midst of the current pandemic, there has been a concerted effort to identify viable ways to conserve PPE, including decontamination after use. Some hospitals have already begun using UV-C light to decontaminate N95 respirators and other PPE, but many lack the space or equipment to implement existing protocols. In this study, we outline a procedure by which PPE may be decontaminated using ultraviolet (UV) radiation in biosafety cabinets (BSCs), a common element of many academic, public health, and hospital laboratories, and discuss the dose ranges needed for effective decontamination of critical PPE. We further discuss obstacles to this approach including the possibility that the UV radiation levels vary within BSCs. Effective decontamination of N95 respirator masks or surgical masks requires UV-C doses of greater than 1 Jcm −2 , which would take a minimum of 4.3 hours per side when placing the N95 at the bottom of the BSCs tested in this study. Elevating the N95 mask by 48 cm (so that it lies 19 cm from the top of the BSC) would enable the delivery of germicidal doses of UV-C in 62 minutes per side. Effective decontamination of face shields likely requires a much lower UV-C dose, and may be achieved by placing the face shields at the bottom of the BSC for 20 minutes per side. Our results are intended to provide support to healthcare organizations looking for alternative methods to extend their reserves of PPE. We recognize that institutions will require robust quality control processes to guarantee the efficacy of any implemented decontamination protocol. We also recognize that in certain situations such institutional resources may not be available; while we subscribe to the general principle that some degree of decontamination is preferable to re-use without decontamination, we would strongly advise that in such cases at least some degree of on-site verification of UV dose delivery be performed.
Background Several prospective studies report improved outcomes with pretreatment nutrition interventions prior to radiation therapy for head and neck cancer (HNC), but none have assessed similar interventions before surgery for HNC. Methods POINT, a pilot randomized controlled trial, was conducted to evaluate a multimodal nutrition intervention. Patients undergoing primary surgery with free flap reconstruction for HNC were randomly assigned to the control arm or a preoperative multimodal nutrition intervention. Results POINT included 49 patients. Nutrition risk scores did not change significantly for either the intervention or control group. Control patients had a significant decrease in body weight in the preoperative period (p < 0.001). Conversely, weight among intervention patients did not significantly decrease (p = 0.680). The intervention mitigated weight loss in patients with dysphagia (p = 0.001). Conclusions Preoperative nutrition optimization shows potential to reduce weight loss normally experienced by patients with head and neck cancer prior to surgical extirpation, especially among those with subjective dysphagia.
Personal protective equipment (PPE) is crucially important to the safety of both patients and medical personnel, particularly in the event of an infectious pandemic. As the incidence of Coronavirus Disease 2019 (COVID-19) increases exponentially in the United States and many parts of the world, healthcare provider demand for these necessities is currently outpacing supply. In the midst of the current pandemic, there has been a concerted effort to identify viable ways to conserve PPE, including decontamination after use. In this study, we outline a procedure by which PPE may be decontaminated using ultraviolet (UV) radiation in biosafety cabinets (BSCs), a common element of many academic, public health, and hospital laboratories. According to the literature, effective decontamination of N95 respirator masks or surgical masks requires UV-C doses of greater than 1 Jcm−2, which was achieved after 4.3 hours per side when placing the N95 at the bottom of the BSCs tested in this study. We then demonstrated complete inactivation of the human coronavirus NL63 on N95 mask material after 15 minutes of UV-C exposure at 61 cm (232 μWcm−2). Our results provide support to healthcare organizations looking for methods to extend their reserves of PPE.
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