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The COVID-19 pandemic has led to an increased demand for mechanical ventilators and concerns of a ventilator shortage. Several groups have advocated for 1 ventilator to ventilate 2 or more patients in the event of such a shortage. However, differences in patient lung mechanics could make sharing a ventilator detrimental to both patients. Our previous study indicated failure to ventilate in 67% of simulations. The safety problems that must be solved include individual control of tidal volume (V

), individual measurement of V

, individualization of PEEP settings, and individual PEEP measurement. The purpose of this study was to evaluate potential solutions developed at our institution.

Two separate lung simulators were ventilated with a modified multiplex circuit using pressure control ventilation. Parameters of the lung models used for simulations (resistance and compliance) were evidence-based from published studies. Individual circuit-modification devices were first evaluated for accuracy. Devices wereults of this simulation-based study indicate that devices for individual control and display of VT and PEEP are effective in extending the usability and potential patient safety of multiplex ventilation.

Pulmonary rehabilitation is an effective treatment for patients with COPD, but patient uptake and adherence to the current offering of center-based pulmonary rehabilitation is modest due to transportation, access, poverty, and frailty, and even more so in the context of the COVID pandemic. Home-based options have been proposed and were found noninferior to center-based rehabilitation; however, there is a lack of home-based programs, and more understanding is needed. We aimed to test the feasibility, uptake, and adherence to a home-based program for COPD rehabilitation with health coaching.

We conducted a randomized trial with a wait-list controlled design to evaluate the effects of a home-based program with health coaching on breathlessness in subjects with moderate to severe COPD unable to attend the regular pulmonary rehabilitation program. The 8-week intervention consisted of video-guided exercises to be done 6 times a week and captured with a computer tablet. Health coaching was done weekly over the tth COPD that cannot attend to the well-established center-based pulmonary rehabilitation. (ClinicalTrials.gov registration NCT02557178.).

The tested home-based rehabilitation program with health coaching was feasible, highly acceptable, showed a high degree of adherence, and improved self-management abilities. This study offers seminal information for home-based rehabilitation programs to design alternative options of rehabilitation to individuals with COPD that cannot attend to the well-established center-based pulmonary rehabilitation. (ClinicalTrials.gov registration NCT02557178.).

Although administration of regional anesthesia nerve blocks has increased during the COVID-19 pandemic, training opportunities in regional anesthesia have reduced. Simulation training may enhance skills, but simulators must be accurate enough for trainees to engage in a realistic way-for example, detection of excessive injection pressure. The soft-embalmed Thiel cadaver is a life-like, durable simulator that is used for dedicated practice and mastery learning training in regional anesthesia. We hypothesized that injection opening pressure in perineural tissue, at epineurium and in subepineurium were similar to opening pressures measured in experimental animals, fresh frozen cadavers, glycol soft-fix cadavers and patients.

We systematically reviewed historical data, then conducted three validation studies delivering a 0.5 mL hydrolocation bolus of embalming fluid and recording injection pressure. First, we delivered the bolus at 12 mL/min at epimysium, perineural tissue, epineurium and in subepineurium at 48 peripheral nerve sites on three cadavers. Second, we delivered the bolus at using three infusion rates 1 mL/min, 6 mL/min and 12 mL/min on epineurium at 70 peripheral nerve sites on five cadavers. Third, we repeated three injections (12 mL/min) at 24 epineural sites over the median and sciatic nerves of three cadavers.

Mean (95%) injection pressure was greater at epineurium compared with subepineurium (geometric ratio 1.2 (95% CI 0.9 to 1.6)), p=0.04, and perineural tissue (geometric ratio 5.1 (95% CI 3.7 to 7.0)), p<0.0001. Mean (95%) injection pressure was greater at 12 mL/min compared with 1 mL/min (geometric ratio 1.6 (95% CI 1.2 to 2.1), p=0.005). Pressure measurements were similar in study 3 (p>0.05 for all comparisons).

We conclude that the soft-embalmed Thiel cadaver is a realistic simulator of injection opening pressure.

We conclude that the soft-embalmed Thiel cadaver is a realistic simulator of injection opening pressure.In this paper, I explore the 2012 face transplant performed on US recipient Richard Norris and how it was represented by the media as a 'makeover story'. Informed by press coverage from the date of the transplant to the present day, I examine a widely viewed and critically acclaimed investigative report that aired on CBS's 60 Minutes entitled 'My Brother's Keeper'. Through a close reading of both its form and content, I claim that the report's makeover story consists of four key themes heroic medicine and miraculous science; appearance-based stigma and social alienation; appearance-based conformity and social assimilation; and subjective alterity and embodied hybridity. In doing so, I contend that the report's themes contain the widespread ambivalence about facial transplantation by confirming prevailing assumptions about medical science and how it creates normal people who live good lives. That said, I also contend that the report's themes complicate these assumptions by highlighting how facial transplantation invariably involves immediate encounters with otherness and corporeal interconnectedness. I conclude that the report's makeover story-characterised as it is by the constraints of the before-and-after format-must be rethought and, ultimately, reworked if we wish to do justice to face transplant recipients.The COVID-19 pandemic has highlighted the need to quickly and reliably prioritize clinically approved compounds for their potential effectiveness for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Here, we deployed algorithms relying on artificial intelligence, network diffusion, and network proximity, tasking each of them to rank 6,340 drugs for their expected efficacy against SARS-CoV-2. To test the predictions, we used as ground truth 918 drugs experimentally screened in VeroE6 cells, as well as the list of drugs in clinical trials that capture the medical community's assessment of drugs with potential COVID-19 efficacy. We find that no single predictive algorithm offers consistently reliable outcomes across all datasets and metrics. This outcome prompted us to develop a multimodal technology that fuses the predictions of all algorithms, finding that a consensus among the different predictive methods consistently exceeds the performance of the best individual pipelines. We screened in human cells the top-ranked drugs, obtaining a 62% success rate, in contrast to the 0.8% hit rate of nonguided screenings. Of the six drugs that reduced viral infection, four could be directly repurposed to treat COVID-19, proposing novel treatments for COVID-19. We also found that 76 of the 77 drugs that successfully reduced viral infection do not bind the proteins targeted by SARS-CoV-2, indicating that these network drugs rely on network-based mechanisms that cannot be identified using docking-based strategies. These advances offer a methodological pathway to identify repurposable drugs for future pathogens and neglected diseases underserved by the costs and extended timeline of de novo drug development.Regional quarantine policies, in which a portion of a population surrounding infections is locked down, are an important tool to contain disease. However, jurisdictional governments-such as cities, counties, states, and countries-act with minimal coordination across borders. We show that a regional quarantine policy's effectiveness depends on whether 1) the network of interactions satisfies a growth balance condition, 2) infections have a short delay in detection, and 3) the government has control over and knowledge of the necessary parts of the network (no leakage of behaviors). As these conditions generally fail to be satisfied, especially when interactions cross borders, we show that substantial improvements are possible if governments are outward looking and proactive triggering quarantines in reaction to neighbors' infection rates, in some cases even before infections are detected internally. We also show that even a few lax governments-those that wait for nontrivial internal infection rates before quarantining-impose substantial costs on the whole system. Our results illustrate the importance of understanding contagion across policy borders and offer a starting point in designing proactive policies for decentralized jurisdictions.Microbial community responses to environmental change are largely associated with ecological processes; however, the potential for microbes to rapidly evolve and adapt remains relatively unexplored in natural environments. To assess how ecological and evolutionary processes simultaneously alter the genetic diversity of a microbiome, we conducted two concurrent experiments in the leaf litter layer of soil over 18 mo across a climate gradient in Southern California. In the first experiment, we reciprocally transplanted microbial communities from five sites to test whether ecological shifts in ecotypes of the abundant bacterium, Curtobacterium, corresponded to past adaptive differentiation. selleck kinase inhibitor In the transplanted communities, ecotypes converged toward that of the native communities growing on a common litter substrate. link2 Moreover, these shifts were correlated with community-weighted mean trait values of the Curtobacterium ecotypes, indicating that some of the trait variation among ecotypes could be explained by local adaptation to climate conditions. In the second experiment, we transplanted an isogenic Curtobacterium strain and tracked genomic mutations associated with the sites across the same climate gradient. Using a combination of genomic and metagenomic approaches, we identified a variety of nonrandom, parallel mutations associated with transplantation, including mutations in genes related to nutrient acquisition, stress response, and exopolysaccharide production. Together, the field experiments demonstrate how both demographic shifts of previously adapted ecotypes and contemporary evolution can alter the diversity of a soil microbiome on the same timescale.Living systems maintain or increase local order by working against the second law of thermodynamics. link3 Thermodynamic consistency is restored as they consume free energy, thereby increasing the net entropy of their environment. Recently introduced estimators for the entropy production rate have provided major insights into the efficiency of important cellular processes. In experiments, however, many degrees of freedom typically remain hidden to the observer, and, in these cases, existing methods are not optimal. Here, by reformulating the problem within an optimization framework, we are able to infer improved bounds on the rate of entropy production from partial measurements of biological systems. Our approach yields provably optimal estimates given certain measurable transition statistics. In contrast to prevailing methods, the improved estimator reveals nonzero entropy production rates even when nonequilibrium processes appear time symmetric and therefore may pretend to obey detailed balance. We demonstrate the broad applicability of this framework by providing improved bounds on the energy consumption rates in a diverse range of biological systems including bacterial flagella motors, growing microtubules, and calcium oscillations within human embryonic kidney cells.

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