Programmable stiffness and shape modulation in origami materials: Emergence of a distant actuation feature

This paper develops an origami based mechanical metamaterial with programmable deformation-dependent stiffness and shape modulation, leading to the realization of a distant actuation feature. Through computational and experimental analyses, we have uncovered that a waterbomb based tubular metamaterial can undergo mixed mode of deformations involving both rigid origami motion and structural deformation. Besides the capability of achieving a near-zero stiffness, a contact phase is identified that initiates a substantial increase in the stiffness with programmable features during deformation of the metamaterial. Initiation of the contact phase as a function of the applied global load can be designed based on the microstructural geometry of the waterbomb bases and their assembly. The tubular metamaterial can exhibit a unique deformation dependent spatially varying mixed mode Poisson’s ratio, which is achievable from a uniform initial configuration of the metamaterial. The spatial profile of the metamaterial can be modulated as a function of the applied far-field global force, and the configuration and assembly of the waterbomb bases. This creates a new possibility of developing a distant actuation feature in the metamaterial enabling us to achieve controlled local actuation through the application of a single far-field force. The distant actuation feature eliminates the need of installing embedded complex network of sensors, actuators and controllers in the material. The fundamental programmable features of the origami metamaterial unravelled in this paper can find wide range of applications in soft robotics, aerospace, biomedical devices and various other advanced physical systems

Curved-crease origami face shields for infection control

The COVID-19 pandemic has created enormous global demand for personal protective equipment (PPE). Face shields are an important component of PPE for front-line workers in the context of the COVID-19 pandemic, providing protection of the face from splashes and sprays of virus-containing fluids. Existing face shield designs and manufacturing procedures may not allow for production and distribution of face shields in sufficient volume to meet global demand, particularly in Low and Middle-Income countries. This paper presents a simple, fast, and cost-effective curved-crease origami technique for transforming flat sheets of flexible plastic material into face shields for infection control. It is further shown that the design could be produced using a variety of manufacturing methods, ranging from manual techniques to high-volume die-cutting and creasing. This demonstrates the potential for the design to be applied in a variety of contexts depending on available materials, manufacturing capabilities and labour. An easily implemented and flexible physical-digital parametric design methodology for rapidly exploring and refining variations on the design is presented, potentially allowing others to adapt the design to accommodate a wide range of ergonomic and protection requirements

Curved-crease origami face shields for infection control

The COVID-19 pandemic has created enormous global demand for personal protective equipment (PPE). Face shields are an important component of PPE for front-line workers in the context of the COVID-19 pandemic, providing protection of the face from splashes and sprays of virus-containing fluids. Existing face shield designs and manufacturing procedures may not allow for production and distribution of face shields in sufficient volume to meet global demand, particularly in Low and Middle-Income countries. This paper presents a simple, fast, and cost-effective curved-crease origami technique for transforming flat sheets of flexible plastic material into face shields for infection control. It is further shown that the design could be produced using a variety of manufacturing methods, ranging from manual techniques to high-volume die-cutting and creasing. This demonstrates the potential for the design to be applied in a variety of contexts depending on available materials, manufacturing capabilities and labour. An easily implemented and flexible physical-digital parametric design methodology for rapidly exploring and refining variations on the design is presented, potentially allowing others to adapt the design to accommodate a wide range of ergonomic and protection requirements

Development and validation of a targeted gene sequencing panel for application to disparate cancers

Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour’s molecular profile. We aimed to develop a targeted gene sequencing panel for application to disparate cancer types with particular focus on tumours of the head and neck, plus test for utility in liquid biopsy. The final panel designed through Roche/Nimblegen combined 451 cancer-associated genes (2.01 Mb target region). 136 patient DNA samples were collected for performance and application testing. Panel sensitivity and precision were measured using well-characterised DNA controls (n = 47), and specificity by Sanger sequencing of the Aryl Hydrocarbon Receptor Interacting Protein (AIP) gene in 89 patients. Assessment of liquid biopsy application employed a pool of synthetic circulating tumour DNA (ctDNA). Library preparation and sequencing were conducted on Illumina-based platforms prior to analysis with our accredited (ISO15189) bioinformatics pipeline. We achieved a mean coverage of 395x, with sensitivity and specificity of >99% and precision of >97%. Liquid biopsy revealed detection to 1.25% variant allele frequency. Application to head and neck tumours/cancers resulted in detection of mutations aligned to published databases. In conclusion, we have developed an analytically-validated panel for application to cancers of disparate types with utility in liquid biopsy

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Quasi-static impact of foldcore sandwich panels

This thesis considered the design of new and improved foldcore sandwich panels suitable for high-performance energy absorption applications. This was achieved by utilising origami geometry design techniques to alter foldcore structures such that they possessed different mechanical behaviours and failure modes. The major findings of this thesis were in three areas as follows. First, a modified planar foldcore geometry was developed by introducing sub-folds into a standard foldcore pattern. The new geometry, deemed the indented foldcore, successfully triggered a high-order failure mode known as a travelling hinge line failure mode. This was found to have a much higher energy absorption than the plate buckling failure mode seen in an unmodified foldcore structure. A comprehensive numerical, theoretical, and experimental analysis was conducted on the indented core, which included the development of a new foldcore prototyping method that utilised 3D printed moulds. It was shown that compared to available commercial honeycomb cores, the indented foldcore had an improved uniformity of energy absorption, but weaker overall peak and crushing stresses. Second, rigid origami design principles were used to develop extended foldcore geometries. New parametrisations were presented for three patterns, to complete a set of Miura-derivative geometries termed first-level derivatives. The first-level derivative parametrisations were then combined to create complex, piecewise geometries, with compatible faceted sandwich face geometry also developed. Finally, a method to generate rigid-foldable, curved-crease geometry from Miura-derivative straight-crease geometry was presented. All geometry was validated with physical prototypes and was compiled into a MATLAB Toolbox. Third, the performance of these extended foldcore geometries under impact loadings was investigated. An investigation of curved-crease foldcores showed that they were stronger than straight-crease foldcores, and at certain configurations can potentially match the strength, energy-absorption under quasi-static impact loads, and out-of-plane stiffness of a honeycomb core. A brief investigation of foldcores under low-velocity impact loadings showed that curved-crease foldcores, unlike straight-crease foldcores, strengthened under dynamic loadings, however not to the same extent as honeycomb. Finally, an investigation of single-curved foldcore sandwich shells was conducted. It was seen that foldcore shells could not match the energy-absorption capability of an over-expanded honeycomb shell, but certain core types did exhibit other attributes that might be exploitable with future research, including superior initial strength and superior uniformity of response.</p