CAR-engineered lymphocyte persistence is governed by a FAS ligand/FAS auto-regulatory circuit.

Chimeric antigen receptor (CAR)-engineered T and NK cells can cause durable remission of B-cell malignancies; however, limited persistence restrains the full potential of these therapies in many patients. The FAS ligand (FAS-L)/FAS pathway governs naturally-occurring lymphocyte homeostasis, yet knowledge of which cells express FAS-L in patients and whether these sources compromise CAR persistence remains incomplete. Here, we constructed a single-cell atlas of diverse cancer types to identify cellular subsets expressing FASLG, the gene encoding FAS-L. We discovered that FASLG is limited primarily to endogenous T cells, NK cells, and CAR-T cells while tumor and stromal cells express minimal FASLG. To establish whether CAR-T/NK cell survival is regulated through FAS-L, we performed competitive fitness assays using lymphocytes modified with or without a FAS dominant negative receptor (ΔFAS). Following adoptive transfer, ΔFAS-expressing CAR-T and CAR-NK cells became enriched across multiple tissues, a phenomenon that mechanistically was reverted through FASLG knockout. By contrast, FASLG was dispensable for CAR-mediated tumor killing. In multiple models, ΔFAS co-expression by CAR-T and CAR-NK enhanced antitumor efficacy compared with CAR cells alone. Together, these findings reveal that CAR-engineered lymphocyte persistence is governed by a FAS-L/FAS auto-regulatory circuit.

The supine moving apprehension test-Reliability and validity among healthy individuals and patients with anterior shoulder instability.

Background: Performance-based tests for patients with anterior shoulder dislocation are lacking. This study determined the reliability and validity of the supine moving apprehension test designed to assess the ability to control anterior instability loads. Methods: Thirty-six participants were recruited (18 healthy individuals, and 18 patients following anterior shoulder dislocation). Healthy participants performed the supine moving apprehension test on 2 separate occasions to determine test-retest reliability. Patients completed the supine moving apprehension test and the Western Ontario Shoulder Instability index before and 6 months after surgical stabilization of their shoulder. The presence of anterior apprehension was also documented post-operatively. Results: The supine moving apprehension test demonstrated good test-retest reliability (intraclass correlation coefficient = 0.74-0.84). Patients performed 18-30 repetitions less than healthy individuals during the supine moving apprehension test (P < 0.01). A strong correlation was found between supine moving apprehension test scores and Western Ontario Shoulder Instability post-operatively (r = -0.74, P ≤ 0.01). Supine moving apprehension test scores significantly improved among patients following surgery (P < 0.01). Patients with a negative apprehension test post-operatively performed the supine moving apprehension test significantly better than patients with a positive apprehension test (P < 0.01). Conclusions: The supine moving apprehension test is reliable and valid among patients with anterior shoulder dislocation and may serve to assess patients' ability to control shoulder anterior instability loads.

Parents' experience of a shared parent-child stay during the first week of hospitalization in a child psychiatry inpatient ward.

Hospitalization of children in an inpatient psychiatric ward is stressful for both the children and their parents, and separation from the parents during hospitalization is probably one major cause of this stress. We designated one room in a closed inpatient unit to enable a parent to stay with his/her child, including overnight, during the 1st week of hospitalization. We then examined the parents' experience of the shared parent-child stay. Thirty parents of 16 children aged 6-12 years admitted to our inpatient child psychiatry ward completed in-depth semi-structured interviews after that week's experience. The interviews covered the parents' experiences of the 1st week in the larger context of pre-hospitalization period, which also includes the decision to hospitalize the child. The contents of the interviews were analyzed by means of independent coders that identified the following major themes: (1) ambivalence and confusion of the parents as related to their decision to hospitalize their child in the time period just before admission; (2) gradual process of separation from the child during the joint stay at the ward; (3) building confidence and trust toward the staff. Themes 2 and 3 express benefits from the joint hospitalization that may have a strong positive impact on the child's and the parent's recovery. These themes warrant further evaluation of the proposed shared stay during hospitalization in future studies.

TAM receptors in phagocytosis: Beyond the mere internalization of particles.

TYRO3, AXL, and MERTK constitute the TAM family of receptor tyrosine kinases, activated by their ligands GAS6 and PROS1. TAMs are necessary for adult homeostasis in the immune, nervous, reproductive, skeletal, and vascular systems. Among additional cellular functions employed by TAMs, phagocytosis is central for tissue health. TAM receptors are dominant in providing phagocytes with the molecular machinery necessary to engulf diverse targets, including apoptotic cells, myelin debris, and portions of live cells in a phosphatidylserine-dependent manner. Simultaneously, TAMs drive the release of anti-inflammatory and tissue repair molecules. Disruption of the TAM-driven phagocytic pathway has detrimental consequences, resulting in autoimmunity, male infertility, blindness, and disrupted vascular integrity, and which is thought to contribute to neurodegenerative diseases. Although structurally and functionally redundant, the TAM receptors and ligands underlie complex signaling cascades, of which several key aspects are yet to be elucidated. We discuss similarities and differences between TAMs and other phagocytic pathways, highlight future directions and how TAMs can be harnessed therapeutically to modulate phagocytosis.

Do patients with Peyronie's disease perceive penile curvature in adults and children differently than the general population?

BACKGROUND: As perception of penile curvature varies widely, we sought to understand how adults perceive curvature and how these opinions compare with those of patients with curvature, specifically Peyronie's disease (PD). AIM: To investigate the perspectives of curvature correction from adults with and without PD, as well as differences within demographics. METHODS: A cross-sectional survey was administered to adult patients and nonpatient companions in general urology clinics at 3 institutions across the United States. Men, women, and nonbinary participants were recruited. Patients were grouped as having PD vs andrology conditions without PD vs general urology conditions plus companions. The survey consisted of unlabeled 2-dimensional images of penis models with varying degrees of curvature. Participants selected images that they would want surgically corrected for themselves and their children. Univariable and multivariable analyses were performed to identify demographic variables associated with willingness to correct. OUTCOMES: Our main outcome was to detect differences in threshold to correct curvature between those with and without PD. RESULTS: Participants were grouped as follows: PD (n = 141), andrology (n = 132), and general (n = 302) . Respectively, 12.8%, 18.9%, and 19.9% chose not to surgically correct any degree of curvature (P = .17). For those who chose surgical correction, the mean threshold for correction was 49.7°, 51.0°, and 51.0° (P = .48); for their children, the decision not to correct any degree of curvature was 21.3%, 25.4%, and 29.3% (P = .34), which was significantly higher than correction for themselves (P < .001). The mean threshold for their children's correction was 47.7°, 53.3°, and 49.4° for the PD, andrology, and general groups (P = .53), with thresholds no different vs themselves (P = .93). On multivariable analysis, no differences were seen in demographics within the PD and andrology groups. In the general group, participants aged 45 to 54 years and those who identified as LGBTQ (lesbian, gay, bisexual, transgender, queer) had a higher threshold for correction as compared with their counterparts when factoring other demographic variables (63.2° vs 48.8°, P = .001; 62.1° vs 50.4°, P = .05). CLINICAL IMPLICATIONS: With changing times and viewpoints, this study stresses the importance of shared decision making and balancing risks and benefits to correction of penile curvature. STRENGTHS AND LIMITATIONS: Strengths include the broad population surveyed. Limitations include the use of artificial models. CONCLUSION: No significant differences were seen in the decision to surgically correct curvature between participants with and without PD, with participants being less likely to choose surgical correction for their children.

Elasticity of whole blood clots measured via Volume Controlled Cavity Expansion.

Measuring and understanding the mechanical properties of blood clots can provide insights into disease progression and the effectiveness of potential treatments. However, several limitations hinder the use of standard mechanical testing methods to measure the response of soft biological tissues, like blood clots. These tissues can be difficult to mount, and are inhomogeneous, irregular in shape, scarce, and valuable. To remedy this, we employ in this work Volume Controlled Cavity Expansion (VCCE), a technique that was recently developed, to measure local mechanical properties of soft materials in their natural environment. Through highly controlled volume expansion of a water bubble at the tip of an injection needle, paired with simultaneous measurement of the resisting pressure, we obtain a local signature of whole blood clot mechanical response. Comparing this data with predictive theoretical models, we find that a 1-term Ogden model is sufficient to capture the nonlinear elastic response observed in our experiments and produces shear modulus values that are comparable to values reported in the literature. Moreover, we find that bovine whole blood stored at 4 °C for greater than 2 days exhibits a statistically significant shift in the shear modulus from 2.53 ± 0.44 kPa on day 2 (N = 13) to 1.23 ± 0.18 kPa on day 3 (N = 14). In contrast to previously reported results, our samples did not exhibit viscoelastic rate sensitivity within strain rates ranging from 0.22 - 21.1 s-1. By surveying existing data on whole blood clots for comparison, we show that this technique provides highly repeatable and reliable results, hence we propose the more widespread adoption of VCCE as a path forward to building a better understanding of the mechanics of soft biological materials.

Torsion-induced stick-slip phenomena in the delamination of soft adhesives.

Soft adhesive contacts are ubiquitous in nature and are increasingly used in synthetic systems, such as flexible electronics and soft robots, due to their advantages over traditional joining techniques. While methods to study the failure of adhesives typically apply tensile loads to the adhesive joint, less is known about the performance of soft adhesives under shear and torsion, which may become important in engineering applications. A major challenge that has hindered the characterization of shear/torsion-induced delamination is imposed by the fact that, even after delamination, contact with the substrate is maintained, thus allowing for frictional sliding and re-adhesion. In this work, we address this gap by studying the controlled delamination of soft cylinders under combined compression and torsion. Our experimental observations expose the nucleation of delamination at an imperfection and its propagation along the circumference of the cylinder. The observed sequence of 'stick-slip' events and the sensitivity of the delamination process to material parameters are explained by a theoretical model that captures axisymmetric delamination patterns, along with the subsequent frictional sliding and re-adhesion. By opening up an avenue for improved characterization of adhesive failure, our experimental approach and theoretical framework can guide the design of adhesives in future applications.

Phagocytosis in the retina promotes local insulin production in the eye.

The retina is highly metabolically active, relying on glucose uptake and aerobic glycolysis. Situated in close contact to photoreceptors, a key function of cells in the retinal pigment epithelium (RPE) is phagocytosis of damaged photoreceptor outer segments (POS). Here we identify RPE as a local source of insulin in the eye that is stimulated by POS phagocytosis. We show that Ins2 messenger RNA and insulin protein are produced by RPE cells and that this production correlates with RPE phagocytosis of POS. Genetic deletion of phagocytic receptors ('loss of function') reduces Ins2, whereas increasing the levels of the phagocytic receptor MerTK ('gain of function') increases Ins2 production in male mice. Contrary to pancreas-derived systemic insulin, RPE-derived local insulin is stimulated during starvation, which also increases RPE phagocytosis. Global or RPE-specific Ins2 gene deletion decreases retinal glucose uptake in starved male mice, dysregulates retinal physiology, causes defects in phototransduction and exacerbates photoreceptor loss in a mouse model of retinitis pigmentosa. Collectively, these data identify RPE cells as a phagocytosis-induced local source of insulin in the retina, with the potential to influence retinal physiology and disease.

The crucial role of elasticity in regulating liquid-liquid phase separation in cells.

Liquid-liquid phase separation has emerged as a fundamental mechanism underlying intracellular organization, with evidence for it being reported in numerous different systems. However, there is a growing concern regarding the lack of quantitative rigor in the techniques employed to study phase separation, and their ability to account for the complex nature of the cellular milieu, which affects key experimentally observable measures, such as the shape, size and transport dynamics of liquid droplets. Here, we bridge this gap by combining recent experimental data with theoretical predictions that capture the subtleties of nonlinear elasticity and fluid transport. We show that within a biologically accessible range of material parameters, phase separation is highly sensitive to elastic properties and can thus be used as a mechanical switch to rapidly transition between different states in cellular systems. Furthermore, we show that this active mechanically mediated mechanism can drive transport across cells at biologically relevant timescales and could play a crucial role in promoting spatial localization of condensates; whether cells exploit such mechanisms for transport of their constituents remains an open question.

Regulation of bone homeostasis by MERTK and TYRO3.

The fine equilibrium of bone homeostasis is maintained by bone-forming osteoblasts and bone-resorbing osteoclasts. Here, we show that TAM receptors MERTK and TYRO3 exert reciprocal effects in osteoblast biology: Osteoblast-targeted deletion of MERTK promotes increased bone mass in healthy mice and mice with cancer-induced bone loss, whereas knockout of TYRO3 in osteoblasts shows the opposite phenotype. Functionally, the interaction of MERTK with its ligand PROS1 negatively regulates osteoblast differentiation via inducing the VAV2-RHOA-ROCK axis leading to increased cell contractility and motility while TYRO3 antagonizes this effect. Consequently, pharmacologic MERTK blockade by the small molecule inhibitor R992 increases osteoblast numbers and bone formation in mice. Furthermore, R992 counteracts cancer-induced bone loss, reduces bone metastasis and prolongs survival in preclinical models of multiple myeloma, breast- and lung cancer. In summary, MERTK and TYRO3 represent potent regulators of bone homeostasis with cell-type specific functions and MERTK blockade represents an osteoanabolic therapy with implications in cancer and beyond.

Outcomes among patients admitted for non-ST-segment myocardial infarction in the pre-pandemic and pandemic COVID-19 era: Israel Nationwide study.

BACKGROUND: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic in 2019, several countries have reported a substantial drop in the number of patients admitted with non-ST-segment myocardial infarction (NSTEMI). OBJECTIVE: We aimed to evaluate the changes in admissions, in-hospital management and outcomes of patients with NSTEMI in the COVID-19 era in a nationwide survey. METHOD: A prospective, multicenter, observational, nationwide study involving 13 medical centers across Israel aimed to evaluate consecutive patients with NSTEMI admitted to intensive cardiac care units over an 8-week period during the COVID-19 outbreak and to compare them with NSTEMI patients admitted at the same period 2 years earlier (control period). RESULTS: There were 624 (43%) NSTEMI patients, of whom 349 (56%) were hospitalized during the COVID-19 era and 275 (44%) during the control period. There were no significant differences in age, gender and other baseline characteristics between the two study periods. During the COVID-19 era, more patients arrived at the hospital via an emergency medical system compared with the control period (P = 0.05). Time from symptom onset to hospital admission was longer in the COVID-19 era as compared with the control period [11.5 h (interquartile range, IQR, 2.5-46.7) vs. 2.9 h (IQR 1.7-6.8), respectively, P < 0.001]. Nevertheless, the time from hospital admission to reperfusion was similar in both groups. The rate of coronary angiography was also similar in both groups. The in-hospital mortality rate was similar in both the COVID-19 era and the control period groups (2.3% vs. 4.7%, respectively, P = 0.149) as was the 30-day mortality rate (3.7% vs. 5.1%, respectively, P = 0.238). CONCLUSION: In contrast to previous reports, admission rates of NSTEMI were similar in this nationwide survey during the COVID-19 era. With longer time from symptoms to admission, but with the same time from hospital admission to reperfusion therapy and with similar in-hospital and 30-day mortality rates. Even in times of crisis, adherence of medical systems to clinical practice guidelines ensures the preservation of good clinical outcomes.

An analysis of factors that influence patient preference of third-line therapy for overactive bladder.

OBJECTIVE: Patients with overactive bladder (OAB) refractory to first- and second-line therapy may pursue third-line therapies, including intradetrusor onabotulinum toxin-A (BTX), peripheral tibial nerve stimulation (PTNS), and sacral neuromodulation (SNM). The factors that influence patient preference for each treatment modality have not yet been explored. This study sought to investigate the specific parameters that patients consider in choosing a third-line therapy for OAB. METHODS: Patients refractory to first- and second-line therapies for OAB were identified in our outpatient clinic and asked to watch an educational video providing information on the risks and benefits of each third-line treatment option. They were then given a questionnaire to rank their preference of therapy and select reasons for why they found each therapy favorable and unfavorable. Patients under age 18 years, non-English speakers, those with a developmental disability, and those with a diagnosis of neurogenic bladder were excluded. RESULTS: Of the 98 patients included in the study, 40 participants (40.8%) chose intradetrusor BTX injections, 34 (34.7%) chose PTNS, and 16 (16.3%) chose SNM as their first choice. Seven patients (7.1%) chose none of the offered therapies, and one patient (1.0%) chose all three therapies with equal preference. BTX was found most attractive for its long efficacy (47%); its least attractive feature was the potential need for self-catheterization due to urinary retention (54%). PTNS was found most attractive for being a nonsurgical option (32%) and having no reported significant complications (39%); its least attractive feature was need for frequent office visits (61%). SNM was found most attractive for its potential for long-term relief without frequent office visits (53%); its least attractive feature was need for an implanted device (33%). Patients opting for SNM had higher scores on Urinary Distress Inventory-6 and Incontinence Impact Questionnaire-7 questionnaires when compared to patients opting for BTX injections or PTNS (p < 0.05). 47.4% of patients eventually pursued a third-line therapy. Of those, there was a 67.6% concordance rate between the therapy patients ranked first and the therapy they eventually underwent. CONCLUSIONS: Patients with more severe OAB symptoms opt for more invasive and less time-consuming therapy with the potential for long-term relief, namely SNM. Despite thorough counseling, many patients do not progress to advanced OAB therapies. Understanding factors that influence patients' affinity toward a specific type of treatment can aid with individualized counseling on third-line OAB therapies.

Targeted suppression of human IBD-associated gut microbiota commensals by phage consortia for treatment of intestinal inflammation.

Human gut commensals are increasingly suggested to impact non-communicable diseases, such as inflammatory bowel diseases (IBD), yet their targeted suppression remains a daunting unmet challenge. In four geographically distinct IBD cohorts (n = 537), we identify a clade of Klebsiella pneumoniae (Kp) strains, featuring a unique antibiotics resistance and mobilome signature, to be strongly associated with disease exacerbation and severity. Transfer of clinical IBD-associated Kp strains into colitis-prone, germ-free, and colonized mice enhances intestinal inflammation. Stepwise generation of a lytic five-phage combination, targeting sensitive and resistant IBD-associated Kp clade members through distinct mechanisms, enables effective Kp suppression in colitis-prone mice, driving an attenuated inflammation and disease severity. Proof-of-concept assessment of Kp-targeting phages in an artificial human gut and in healthy volunteers demonstrates gastric acid-dependent phage resilience, safety, and viability in the lower gut. Collectively, we demonstrate the feasibility of orally administered combination phage therapy in avoiding resistance, while effectively inhibiting non-communicable disease-contributing pathobionts.

Exodus: sequencing-based pipeline for quantification of pooled variants.

SUMMARY: Next-Generation Sequencing is widely used as a tool for identifying and quantifying microorganisms pooled together in either natural or designed samples. However, a prominent obstacle is achieving correct quantification when the pooled microbes are genetically related. In such cases, the outcome mostly depends on the method used for assigning reads to the individual targets. To address this challenge, we have developed Exodus-a reference-based Python algorithm for quantification of genomes, including those that are highly similar, when they are sequenced together in a single mix. To test Exodus' performance, we generated both empirical and in silico next-generation sequencing data of mixed genomes. When applying Exodus to these data, we observed median error rates varying between 0% and 0.21% as a function of the complexity of the mix. Importantly, no false negatives were recorded, demonstrating that Exodus' likelihood of missing an existing genome is very low, even if the genome's relative abundance is low and similar genomes are present in the same mix. Taken together, these data position Exodus as a reliable tool for identifying and quantifying genomes in mixed samples. Exodus is open source and free to use at: https://github.com/ilyavs/exodus. AVAILABILITY AND IMPLEMENTATION: Exodus is implemented in Python within a Snakemake framework. It is available on GitHub alongside a docker containing the required dependencies: https://github.com/ilyavs/exodus. The data underlying this article will be shared on reasonable request to the corresponding author. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Human mitochondrial RNA modifications associate with tissue-specific changes in gene expression, and are affected by sunlight and UV exposure.

RNA-DNA differences (RDD) have previously been identified in the human mitochondrial RNA (mt-RNA) transcripts, yet their functional impact is poorly understood. By analyzing 4928 RNA-seq samples from 23 body sites, we found that mtDNA gene expression negatively correlated with the levels of both m1A 947 16 S rRNA modification (mtDNA position 2617) and the m1A 1812 ND5 mRNA modification (mtDNA position 13,710) in 15 and 14 body sites, respectively. Such correlation was not evident in all tested brain tissues, thus suggesting a tissue-specific impact of these modifications on mtDNA gene expression. To assess the response of the tested modifications to environmental cues, we analyzed pairs of skin samples that were either exposed to the sun or not. We found that the correlations of mtDNA gene expression with both mt-RNA modifications were compromised upon sun exposure. As a first step to explore the underlying mechanism, we analyzed RNA-seq data from keratinocytes that were exposed to increasing doses of UV irradiation. Similar to sun exposure, we found a significant decrease in mtDNA gene expression upon increase in UV dosage. In contrast, there was a significant increase in the m1A 947 16 S rRNA modification levels upon elevation in UV dose. Finally, we identified candidate modulators of such responses. Taken together, our results indicate that mt-RNA modifications functionally correlate with mtDNA gene expression, and responds to environmental cues, hence supporting their physiological importance.

Mutant C. elegans mitofusin leads to selective removal of mtDNA heteroplasmic deletions across generations to maintain fitness.

BACKGROUND: Mitochondrial DNA (mtDNA) is present at high copy numbers in animal cells, and though characterized by a single haplotype in each individual due to maternal germline inheritance, deleterious mutations and intact mtDNA molecules frequently co-exist (heteroplasmy). A number of factors, such as replicative segregation, mitochondrial bottlenecks, and selection, may modulate the exitance of heteroplasmic mutations. Since such mutations may have pathological consequences, they likely survive and are inherited due to functional complementation via the intracellular mitochondrial network. Here, we hypothesized that compromised mitochondrial fusion would hamper such complementation, thereby affecting heteroplasmy inheritance. RESULTS: We assessed heteroplasmy levels in three Caenorhabditis elegans strains carrying different heteroplasmic mtDNA deletions (ΔmtDNA) in the background of mutant mitofusin (fzo-1). Animals displayed severe embryonic lethality and developmental delay. Strikingly, observed phenotypes were relieved during subsequent generations in association with complete loss of ΔmtDNA molecules. Moreover, deletion loss rates were negatively correlated with the size of mtDNA deletions, suggesting that mitochondrial fusion is essential and sensitive to the nature of the heteroplasmic mtDNA mutations. Introducing the ΔmtDNA into a fzo-1;pdr-1;+/ΔmtDNA (PARKIN ortholog) double mutant resulted in a skewed Mendelian progeny distribution, in contrast to the normal distribution in the fzo-1;+/ΔmtDNA mutant, and severely reduced brood size. Notably, the ΔmtDNA was lost across generations in association with improved phenotypes. CONCLUSIONS: Taken together, our findings show that when mitochondrial fusion is compromised, deleterious heteroplasmic mutations cannot evade natural selection while inherited through generations. Moreover, our findings underline the importance of cross-talk between mitochondrial fusion and mitophagy in modulating the inheritance of mtDNA heteroplasmy.

Flow synthesis of photocatalytic semiconductor-metal hybrid nanocrystals.

Semiconductor-metal hybrid nanostructures are promising materials for photocatalytic applications, providing high efficiencies compared to their composing counterparts. So far, the synthesis of such hybrid nanoparticles was limited to batch reactors, achieving tunability while demonstrating how each of the nanocrystals' characteristics affects photocatalytic performances. Yet, new methodologies should be established to increase the synthetic yield while maintaining high control over the resulting structures. Herein, scalable advanced flow techniques are introduced, yielding ZnSe-metal hybrid nanoparticles either in a thermal growth or photo-induced growth regime. Firstly, thermal gold growth in the flow reactor is achieved with good control over the metal tip size and the nanoparticle morphology. We address the dependence of the reaction on temperature, the precursor to nanorod molar ratios, and additional parameters. Additionally, light-induced growth by the flow reactor is demonstrated for platinum clusters. The quality of the resulting hybrids is directly demonstrated by their functionality in photocatalytic hydrogen generation by water reduction, displaying enhanced activity compared to bare ZnSe nanorods. The fairly straightforward adaptation of such powerful flow-reaction techniques to scale-up photocatalytic hybrid nanoparticle syntheses takes them one step forwards towards the realization of their potential in real-life application scenarios.

Investigation of abrasive saw kickback.

Saw kickback can cause fatal injuries, but only woodcutting saws have regulations and assessment methodologies for kickback. These regulations do not apply to abrasive cutting saws, as their cutting mechanism and dominant kickback mode differ from those of woodcutting saws. This work combines theoretical and experimental tools to investigate abrasive saw kickback. A theoretical model based on frictional engagement during a pinch-based kickback event is shown to predict resultant kickback energy in good agreement with experimental measurements. These measurements were obtained using a specialized machine that generates pinch-based kickback events and measures resultant kickback energy. Upon validating the model, two representative saws, a circular cutoff saw and a chainsaw, were tested using the prototype machine to evaluate their comparative kickback risk. This work demonstrates that pinch-based kickback is a potential safety risk for abrasive cutting saw operators and provides a testing machine design and analytical framework for evaluating this risk.

Interfacial cavitation.

Cavitation has long been recognized as a crucial predictor, or precursor, to the ultimate failure of various materials, ranging from ductile metals to soft and biological materials. Traditionally, cavitation in solids is defined as an unstable expansion of a void or a defect within a material. The critical applied load needed to trigger this instability -- the critical pressure -- is a lengthscale independent material property and has been predicted by numerous theoretical studies for a breadth of constitutive models. While these studies usually assume that cavitation initiates from defects in the bulk of an otherwise homogeneous medium, an alternative and potentially more ubiquitous scenario can occur if the defects are found at interfaces between two distinct media within the body. Such interfaces are becoming increasingly common in modern materials with the use of multimaterial composites and layer-by-layer additive manufacturing methods. However, a criterion to determine the threshold for interfacial failure, in analogy to the bulk cavitation limit, has yet to be reported. In this work, we fill this gap. Our theoretical model captures a lengthscale independent limit for interfacial cavitation, and is shown to agree with our observations at two distinct lengthscales, via two different experimental systems. To further understand the competition between the two cavitation modes (bulk versus interface), we expand our investigation beyond the elastic response to understand the ensuing unstable propagation of delamination at the interface. A phase diagram summarizes these results, showing regimes in which interfacial failure becomes the dominant mechanism.