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Owing to high water content and homogeneous texture, conventional hydrogels hardly reach satisfactory mechanical performance. Tensile‐resistant groups and structural heterogeneity are employed to fabricate tough hydrogels. However, those techniques significantly increase the complexity and cost of material synthesis, and have only limited applicability. Here, it is shown that ultra‐tough hydrogels can be obtained via a unique hierarchical architecture composed of chemically coupled self‐assembly units. The associative energy dissipation among them may be rationally engineered to yield libraries of tough gels with self‐healing capability. Tunable tensile strength, fracture strain, and toughness of up to 19.6 MPa, 20 000%, and 135.7 MJ cm⁻ 3 are achieved, all of which exceed the best known records. The results demonstrate a universal strategy to prepare desired ultra‐tough hydrogels in predictable and controllable manners.

IntroductionNon-tuberculosis mycobacterial pulmonary disease (NTM-PD) commonly affects a frail, multi-comorbid population, and treatment involves extended courses of multi-antibiotic therapy with a vast side effect profile. Whilst specialist tuberculosis clinics are commonplace in most UK hospitals, NTM-PD patients are typically managed across various respiratory clinics. We present data on the management of NTM-PD in our centre over a six-year period and propose a case for a specialist NTM service with specialist nurse involvement to improve patient outcomes.MethodsWe retrospectively collected data from 2016 to 2021 on patients with NTM isolated from sputum, bronchoalveolar lavage, pleural fluid or lung biopsy. Cystic fibrosis patients and patients under 18 years old were excluded. A broad range of data were collected, including microbiology, comorbidities, imaging, investigations, treatment and outcomes. We compared the management of patients seen in Specialist (tuberculosis or bronchiectasis) Clinics (SC) with patients in General Respiratory Clinic (GRC).ResultsBetween 2016 and 2021 we identified 459 positive pulmonary NTM cultures from 158 patients. Eight patients grew more than one NTM organism over the five-year period resulting in 170 cases total. ATS diagnostic criteria was met in 104 cases and 87 of these were clinically diagnosed with NTM-PD by respiratory consultants, with 17 probable contaminants. The average age of the NTM-PD patients was 68 years, 64.4% were female, and patients had an average of 2.8 comorbidities. Fifty-six patients started treatment. Of these, 33 were managed in a SC and 23 in a GRC. In the GRC group, only 4.5% of patients completed all required pre-treatment investigations compared with 40.6% in SC. HIV status was checked in 32.1% of GRC patients compared with 39.0% of SC patients. In the SC group, 78.8% of patients had contact with a specialist nurse compared to 26.1% in GRC. At the time of data collection 23 patient had completed treatment. Culture conversion was achieved in 25.0% of GRC patients compared to 53.3% in SC.ConclusionOur data reflects the complexity of managing NTM-PD and demonstrates improved management when receiving care in specialist clinics, thus supporting our case for a specialist NTM service with specialist nurse involvement.

BackgroundAmikacin liposome inhalation suspension (ALIS) is the first FDA-approved treatment included in a combination antibacterial drug regimen for adults with refractory Mycobacterium avium complex lung disease (MAC-LD) who have limited or no alternative treatment options. This study used qualitative research methods via one-on-one interviews to gain insight into real-world patient perspectives and practices to mitigate adverse effects (AEs) associated with ALIS.MethodsAdults in the United States were recruited through the patient support program. Patients who received ALIS for ≥7 consecutive days and self-reported a clinician-confirmed diagnosis of refractory MAC-LD were included. A sample size of 20 patients was targeted. Purposive sampling was used to ensure representation of patients with different ALIS therapy durations. Team members trained in qualitative data collection techniques used a semi-structured interview guide with open-ended questions and follow-up probes to conduct patient interviews via phone. Transcripts were coded and analysed using ATLAS.ti v8.ResultsInvitations were sent to 839 patients; 95 patients completed the screening survey and 41 were eligible. Interviews were conducted with 20 patients (mean age, 48.7 years; 90% white; 80% women; mean ALIS duration, 5.45 months). At the time of interview, 15 patients (75%) had experience receiving ALIS for longer than 1 month, and 13 patients (65%) were currently receiving ALIS treatment.Patients described 44 unique AE mitigation strategies, which can be described using 3 categories (figure 1). Most strategies were used to mitigate respiratory AEs. Common strategies (≥50%) included use of relevant informational materials, localized management of throat irritation, and symptom management to reduce fatigue. Concept saturation was achieved, as no new strategies were identified in the last 5 interviews.Abstract P93 Figure 1Proportion of interviewed patients (N=20) Reporting use of AE mitigation strategies intended toSummaryMitigation strategies intended to prepare patients for ALIS treatment, prevent the increased emergence of certain AEs, and mitigate impact of AEs on treatment persistence may have clinical relevance for treatment of MAC-LD with ALIS. Real-world data identified the diverse set of AE mitigation strategies used by patients and also opportunities clinicians can avail of and adopt in improving adherence to ALIS treatment. These qualitative data can inform future studies to further quantify the effectiveness of AE mitigation strategies in real-world settings.Please refer to page A289 for declarations of interest related to this abstract.

Spider silk is a natural polymeric fiber with high tensile strength, toughness, and has distinct thermal, optical, and biocompatible properties. The mechanical properties of spider silk are ascribed to its hierarchical structure, including primary and secondary structures of the spidroins (spider silk proteins), the nanofibril, the “core–shell”, and the “nano‐fishnet” structures. In addition, spider silk also exhibits remarkable properties regarding humidity/water response, water collection, light transmission, thermal conductance, and shape‐memory effect. This motivates researchers to prepare artificial functional fibers mimicking spider silk. In this review, the authors summarize the study of the structure and properties of natural spider silk, and the biomimetic preparation of artificial fibers from different types of molecules and polymers by taking some examples of artificial fibers exhibiting these interesting properties. In conclusion, biomimetic studies have yielded several noteworthy findings in artificial fibers with different functions, and this review aims to provide indications for biomimetic studies of functional fibers that approach and exceed the properties of natural spider silk. The authors summarize the study of the structure and properties of natural spider silk, and the biomimetic preparation of artificial fibers from different types of materials by taking some examples of artificial fibers exhibiting these interesting properties. This review aims to provide indications for biomimetic studies of functional fibers that approach and exceed the properties of natural spider silk.

Tough hydrogel has attracted considerable interest in various fields, however, due to poor biocompatibility, nondegradation, and pronounced compositional differences from natural tissues, it is difficult to be used for tissue regeneration. Here, a gelatin‐based tough hydrogel (GBTH) is proposed to fill this gap. Inspired by human exercise to improve muscle strength, the synergistic effect is utilized to generate highly functional crystalline domains for resisting crack propagation. The GBTH exhibits excellent tensile strength of 6.67 MPa (145‐fold that after untreated gelation). Furthermore, it is directly sutured to a ruptured tendon of adult rabbits due to its pronounced toughness and biocompatibility, self‐degradability in vivo, and similarity to natural tissue components. Ruptured tendons can compensate for mechanotransduction by GBTH and stimulate tendon differentiation to quickly return to the initial state, that is, within eight weeks. This strategy provides a new avenue for preparation of highly biocompatible tough hydrogel for tissue regeneration. Inspired by human muscle strengthening, tough gelatin hydrogel is prepared by directed training and ion‐induced synergistic crystallization. Furthermore, tough gelatin hydrogel can be implanted into the body to repair damaged tendons due to their high toughness and biocompatibility. Tough gelatin hydrogel is expected to be an ideal material for tendon repair.

This paper focuses on the amount of functional structure and on the Voice properties of complement clauses in tough-constructions, on the basis of previously unexplored variation patterns in Italo-Romance. Cross-dialectal data from various regions of Italy (north, south, extreme south, and islands) show that two main syntactic types of tough-constructions are attested, interacting with the complementation strategies available in each variety. In Type 1, the embedded clause is a VoiceP with an infinitive; in Type 2, the embedded clause is a full TP or a CP and its verb (non-finite or finite) has either passive morphology or a resumptive object clitic. In light of this distribution, I propose that heavily reduced clauses have a passive-like argument realisation pattern (as in Type 1), in contrast with larger clauses (as in Type 2) which behave in a standard way despite being more heterogeneous. This claim supports an extension of current accounts of clausal complementation in Italo-Romance to one more pattern.

HighlightsThe skin-inspired multifunctional ultra-tough electronic skin with tunable mechanical properties was developed by a physically cross-linking salting-freezing-thawing method.The hydrogel integrates transparency (>60%), super toughness (up to 13.96 MJ m−3), good antibacterial properties (E. coli and S. aureus), UV protection (Filtration: 80%–90%), high electrical conductivity (4.72 S m−1), anti-swelling and recyclability.As a human–machine interface, it can be used for complex underwater activities, information encryption/decryption and finger joint rehabilitation training. Multifunctional supramolecular ultra-tough bionic e-skin with unique durability for human–machine interaction in complex scenarios still remains challenging. Herein, we develop a skin-inspired ultra-tough e-skin with tunable mechanical properties by a physical cross-linking salting-freezing-thawing method. The gelling agent (β-Glycerophosphate sodium: Gp) induces the aggregation and binding of PVA molecular chains and thereby toughens them (stress up to 5.79 MPa, toughness up to 13.96 MJ m−3). Notably, due to molecular self-assembly, hydrogels can be fully recycled and reprocessed by direct heating (100 °C for a few seconds), and the tensile strength can still be maintained at about 100% after six recoveries. The hydrogel integrates transparency (> 60%), super toughness (up to 13.96 MJ m−3, bearing 1500 times of its own tensile weight), good antibacterial properties (E. coli and S. aureus), UV protection (Filtration: 80%–90%), high electrical conductivity (4.72 S m−1), anti-swelling and recyclability. The hydrogel can not only monitor daily physiological activities, but also be used for complex activities underwater and message encryption/decryption. We also used it to create a complete finger joint rehabilitation system with an interactive interface that dynamically presents the user’s health status. Our multifunctional electronic skin will have a profound impact on the future of new rehabilitation medical, human–machine interaction, VR/AR and the metaverse fields.

Tough soft materials usually show strain softening and inelastic deformation. Here, we study the molecular mechanism of abnormally large nonsoftening, quasi-linear but inelastic deformation in tough hydrogels made of hyperconnective physical network and linear polymers as molecular glues to the network. The interplay of hyperconnectivity of network and effective load transfer by molecular glues prevents stress concentration, which is revealed by an affine deformation of the network to the bulk deformation up to sample failure. The suppression of local stress concentration and strain amplification plays a key role in avoiding necking or strain softening and endows the gels with a unique large nonsoftening, quasi-linear but inelastic deformation.

BackgroundArikayce was introduced in the UK as add-on therapy for patients with treatment-refractory mycobacterium avium complex (MAC).1 This review examined the outcomes of patients treated with Arikayce.MethodEligible patients were identified through clinical, microbiological and radiological review. Patients were given a Drug Response Assessment (safety test-dosing) before starting Arikayce (590 mg OD) and followed clinically to determine treatment tolerability and sputum cultures.ResultsOur cohort comprises 11 patients, one of the largest in Europe. Patients with refractory MAC had coexistent bronchiectasis, COPD or ILD; 10F/1M, 37–78 yrs, FEV10.52l-2.71l (table 1). 2 patients failed the DRA. Of the remaining 9, within 6 mts’ treatment, 1 culture converted, 2 failed to culture convert and stopped Arikayce. 5 others remain on Arikayce, and 1 stopped because of intolerance. Side effects reported include cough, dysphonia and dyspnoea, which some patients manage by stopping/restarting or taking on alternate days.Abstract P90 Table 1Pt no. F/M Age (yrs) Hx* In pt/OP DRA date FEV1(l) FEV1% pred Arikayce: mts on Rx Reported s/e 4 F 37 1 OP 11/22 2.30 66 >6 nil 7 F 60 1 OP 03/23 2.29 83 <6 voice 8 M 69 2 OP 02/23 2.71 91 <6 u/k 9 F 73 1 IP 06/03 1.85 90 <6 voice 10 F 68 1 OP 05/05 2.62 108 <6 voice 11 F 48 3 IP 01/06 1.34 45 <6 cough, headache, SOB, wheeze 6 F 64 1 OP 12/22 1.34 51 Stopped at 2 due to s/e weak, nauseous, cough, rash, chest tightness 3 F 68 1 OP 11/22 1.10 40 Stopped at 6 due to culture SOB 1 F 78 1 OP 11/22 1.54 83 Stopped at ~6 due to culture cough, voice 2 F 59 1 IP 11/22 1.18 52 0 5 F 67 3 IP 12/22 0.52 23 0 *KEY1 Bx, refr MAC, on standard Rx2 No Bx, IPF, refr MAC, on standard Rx3 No Bx, COPD, refr MAC, intol of standard RxDiscussionTreatment of refractory patients with MAC is challenging. To date 1/3 patients on Arikayce for 6 mts culture converted, reflecting the CONVERT study.1 Side effects were commonly reported, but most patients were able to continue the medication.ReferenceGriffith D, et al. Am J Crit Care Med 2018;198(12):1559–1569.Please refer to page A289 for declarations of interest related to this abstract.

IntroductionRespiratory fungal infections are increasingly encountered in clinical practice and can lead to life threatening invasive diseases. A multi-disciplinary approach has been recommended to provide comprehensive medical care for patients with fungal disease. The Imperial Healthcare NHS Trust Fungal MDT meeting was established in 2017 to discuss patients with suspected fungal disease.AimTo assess the impact of the Fungal MDT discussion on clinical management of patients with suspected pulmonary fungal disease.MethodThe MDT comprising of Respiratory physicians, Microbiologist, Mycologist, Radiologist, Haematologist, and an Infection pharmacist convened monthly. Data was collected from the first MDT discussion in 250 consecutive patients from 2017 to 2021.ResultsFrom the 250 patients, 39% were referred to the MDT to guide management and 22% to establish a diagnosis. Advice on diagnosis and management were sought in 32%. At first MDT discussion a diagnosis was made in 62% of patients and the MDT requested further investigations in 66%. MDT discussion resulted in a change in management in 62% of patients including a change in treatment duration in 22%, commencing antifungal therapy in 13% and stopping treatment in 9% of patients.An underlying respiratory diagnosis was present in 45% of patients with 49% receiving systemic immunosuppression for either renal or haematological conditions. The commonest underlying respiratory diseases were chronic obstructive pulmonary disease (18%) and bronchiectasis (17%). The most common diagnosis was invasive fungal disease occurring in 21% of patients with 10% having semi-invasive fungal disease, 14% chronic pulmonary aspergillosis and 5% allergic bronchopulmonary aspergillosis. Non-fungal disease was diagnosed in 21% of patients. Concomitant bacterial infection was present in 49% of patients.ConclusionIn our centre, Fungal MDT discussion led to the diagnosis or change in management in 62% of patients referred. Fungal MDTs may be useful in centres with a large population of immunocompromised patients or chronic respiratory disease to increase diagnostic certainty, guide management and promote anti-fungal stewardship in a complex case load.