A Multiscale Framework for the Characterization of Damage in Textile Composites Under Thermomechanical Loads

This work examines composite failure at multiple scales. The first scale that is examined is the fiber-matrix scale, where fibers and matrix are discretely modeled. A model is developed at this scale which includes randomness in the fiber positions. This randomness is found to significantly influence the stress field and resulting failure that occurs under thermo mechanical loads as compared to fiber-matrix microstructures with regular arrays of fibers. The fiber-matrix model is utilized to characterize variability and temperature dependence of the composite strength arising from microstructural randomness and the presence of thermally induced stresses. The second scale that is examined is that of a textile unit cell. Failure initiation behavior is examined for a variety of thermo mechanical loadings at this scale, and it is found that failure tends to initiate in a limited number of ways for a wide variety of loadings. A new progressive failure model is then examined for the textile unit cell. This model utilizes cohesive interface elements in the tows, neat matrix pockets, and tow and matrix interfaces to account for crack opening in the textile, as well as a continuum damage model to account for diffuse damage in the tows. Variability and temperature dependence of the transverse tow strength is introduced by specifying varying cohesive strengths in the intra-tow cohesive zones using a Weibull distribution characterized using the random fiber-matrix model. Progressive failure analyses are then performed for the textile unit cell under a variety of thermomechanical loads, and the resulting behaviors are compared to identify characteristic modes of damage development and their effect on the textile response. A continuum damage model for the textile material, which can be applied to engineering structures, is developed based on the characteristic damage modes observed in the textile unit cell analyses. This model tracks the evolution of each characteristic mode of damage based on the structural-scale stress and predicts the degradation in the textile response as a result of this damage. The ability of this model to predict the textile’s response under various damage-inducing loads is then compared to the response obtained from textile unit cell progressive failure analysis, and both models are found to be in good agreement for most loadings

Prediction of Damage Zone Growth in Composites Using Continuum Damage Mechanics

The continuum damage mechanics (CDM) approach is widely used to model damage in polymer matrix composite materials which are represented using the homogenized properties of the fiber and matrix constituents. CDM simplifies the problem of accounting for a large number of defects in a material by considering the homogenized effect of the defects as a change in constitutive properties of the material. However, recent investigations of textile composites have shown that CDM inaccurately predicts the direction of damage zone growth for some composite architectures which fail under shear load, tending to predict failure transverse to the fibers. This behavior is fundamentally attributable to the fact that shear failure in textiles results in large (tow-scale) matrix cracks, while CDM is intended to model distributed micro-cracks. It is shown that when CDM is used to model shear failure in anisotropic continua, material anisotropy tends to cause CDM to predict failure contrary to what is expected for these structures. An approach is presented that may allow CDM to better predict damage growth for shear failure in composites by encouraging the creation of an intial damage zone with sufficient directional bias to overcome the effect of material anisotropy

Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial

We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19. In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978. Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50–72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74–1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67–1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74–1·58]; BRII-196 plus BRII-198 1·00 [0·68–1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91–1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88–1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90. Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19. US National Institutes of Health and Operation Warp Spee