A tidal lung simulation to quantify lung heterogeneity with the Inspired Sinewave Test

We have created a lung simulation to quantify lung heterogeneity from the results of the inspired sinewave test (IST). The IST is a lung function test that is non-invasive, non-ionising and does not require patients' cooperation. A tidal lung simulation is developed to assess this test and also a method is proposed to calculate lung heterogeneity from IST results. A sensitivity analysis based on the Morris method and linear regression were applied to verify and to validate the simulation. Additionally, simulated emphysema and pulmonary embolism conditions were created using the simulation to assess the ability of the IST to identify these conditions. Experimental data from five pigs (pre-injured vs injured) were used for validation. This paper contributes to the development of the IST. Firstly, our sensitivity analysis reveals that the IST is highly accurate with an underestimation of about 5% of the simulated values. Sensitivity analysis suggested that both instability in tidal volume and extreme expiratory flow coefficients during the test cause random errors in the IST results. Secondly, the ratios of IST results obtained at two tracer gas oscillation frequencies can identify lung heterogeneity (ELV60/ELV180 and Qp60/Qp180). There was dissimilarity between simulated emphysema and pulmonary embolism (p < 0:0001). In the animal model, the control group had ELV60/ELV180 = 0.58 compared with 0.39 in injured animals (p < 0.0001)

Sustainable personal protective clothing for healthcare applications: A review

Personal protective equipment (PPE) is critical to protect healthcare workers (HCWs) from highly infectious diseases such as COVID-19. However, hospitals have been at risk of running out of the safe and effective PPE including personal protective clothing needed to treat patients with COVID-19, due to unprecedented global demand. In addition, there are only limited manufacturing facilities of such clothing available worldwide, due to a lack of available knowledge about relevant technologies, ineffective supply chains, and stringent regulatory requirements. Therefore, there remains a clear unmet need for coordinating the actions and efforts from scientists, engineers, manufacturers, suppliers, and regulatory bodies to develop and produce safe and effective protective clothing using the technologies that are locally available around the world. In this review, we discuss currently used PPE, their quality, and the associated regulatory standards. We survey the current state-of-the-art antimicrobial functional finishes on fabrics to protect the wearer against viruses and bacteria and provide an overview of protective medical fabric manufacturing techniques, their supply chains, and the environmental impacts of current single-use synthetic fiber-based protective clothing. Finally, we discuss future research directions, which include increasing efficiency, safety, and availability of personal protective clothing worldwide without conferring environmental problems

Timing the Landmark Events in the Evolution of Clear Cell Renal Cell Cancer: TRACERx Renal.

Clear cell renal cell carcinoma (ccRCC) is characterized by near-universal loss of the short arm of chromosome 3, deleting several tumor suppressor genes. We analyzed whole genomes from 95 biopsies across 33 patients with clear cell renal cell carcinoma. We find hotspots of point mutations in the 5' UTR of TERT, targeting a MYC-MAX-MAD1 repressor associated with telomere lengthening. The most common structural abnormality generates simultaneous 3p loss and 5q gain (36% patients), typically through chromothripsis. This event occurs in childhood or adolescence, generally as the initiating event that precedes emergence of the tumor's most recent common ancestor by years to decades. Similar genomic changes drive inherited ccRCC. Modeling differences in age incidence between inherited and sporadic cancers suggests that the number of cells with 3p loss capable of initiating sporadic tumors is no more than a few hundred. Early development of ccRCC follows well-defined evolutionary trajectories, offering opportunity for early intervention

Copy number signatures and mutational processes in ovarian carcinoma.

The genomic complexity of profound copy number aberrations has prevented effective molecular stratification of ovarian cancers. Here, to decode this complexity, we derived copy number signatures from shallow whole-genome sequencing of 117 high-grade serous ovarian cancer (HGSOC) cases, which were validated on 527 independent cases. We show that HGSOC comprises a continuum of genomes shaped by multiple mutational processes that result in known patterns of genomic aberration. Copy number signature exposures at diagnosis predict both overall survival and the probability of platinum-resistant relapse. Measurement of signature exposures provides a rational framework to choose combination treatments that target multiple mutational processes.NIHR, Ovarian Cancer Action, Cancer Research UK Cambridge Centre, Cambridge Experimental Cancer Medicine Centr

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Intravascular oxygen sensors with novel applications for bedside respiratory monitoring

Measurement allows us to quantify various parameters and variables in natural systems. In addition, by measuring the effect by which a perturbation of one part of the system influences the system as a whole, insights into the functional mechanisms of the system can be inferred. Clinical monitoring has a different role to that of scientific measurement. Monitoring describes measurements whose prime purpose is not to give insights into underlying mechanisms, but to provide information to 'warn' of imminent events. What is often more important is the description of trends in measured variables. In this article, we give some examples - focussed around oxygen sensors - of how new sensors can make important measurements and might in the future contribute to improved clinical management