Flecainide induces a sustained countercurrent dependent effect on RyR2 in permeabilized WT ventricular myocytes but not in intact cells.

Background and purpose: While flecainide is now an accepted treatment for arrhythmias associated with catecholaminergic polymorphic ventricular tachycardia (CPVT), its mechanism of action remains controversial. In studies on myocytes from CPVT mice, inhibition of proarrhythmic Ca2+ waves was initially attributed to a novel action on the type-2 ryanodine receptor (RyR2). However, subsequent work on wild type (WT) myocytes questioned the conclusion that flecainide has a direct action on RyR2. In the present study, the effects of flecainide were compared in intact and permeabilized WT myocytes. Experimental approach: Intracellular Ca2+ was measured using confocal microscopy in intact or saponin permeabilized adult rat ventricular myocytes (ARVM). In some experiments on permeabilized cells, flecainide was studied following partial inhibition of the sarcoplasmic reticulum (SR) counter-current. Key results: Flecainide induced sustained changes Ca2+ sparks and waves in permeabilized ARVM, which were comparable to those reported in intact or permeabilized myocytes from CPVT mice. However, a relatively high level of flecainide (25 µM) was required to induce these effects. Inhibition of the SR counter-current potentiated the effects of flecainide on SR Ca2+ waves. In intact field stimulated ARVM, prolonged exposure to 15 µM flecainide decreased wave frequency but RyR2 dependent effects on Ca2+ sparks were absent; higher drug concentrations blocked field stimulation, consistent with inhibition of Nav1.5. Conclusions and implications: In intact ARVM, the absence of effects on Ca2+ sparks suggests that the intracellular flecainide concentration was insufficient to influence RyR2. Wave inhibition in intact ARVM may reflect secondary effects of Nav1.5 inhibition. Potentiation of flecainide's action by counter-current inhibition can be explained if transient polarization of the SR membrane during SR Ca2+ release facilitates its action on RyR2.

Risk of Aneurysm Rupture (ROAR) study: protocol for a long-term, longitudinal, UK multicentre study of unruptured intracranial aneurysms.

INTRODUCTION: Unruptured intracranial aneurysms (UIA) are common in the adult population, but only a relatively small proportion will rupture. It is therefore essential to have accurate estimates of rupture risk to target treatment towards those who stand to benefit and avoid exposing patients to the risks of unnecessary treatment. The best available UIA natural history data are the PHASES study. However, this has never been validated and given the known heterogeneity in the populations, methods and biases of the constituent studies, there is a need to do so. There are also many potential predictors not considered in PHASES that require evaluation, and the estimated rupture risk is largely based on short-term follow-up (mostly 1 year). The aims of this study are to: (1) test the accuracy of PHASES in a UK population, (2) evaluate additional predictors of rupture and (3) assess long-term UIA rupture rates. METHODS AND ANALYSIS: The Risk of Aneurysm Rupture study is a longitudinal multicentre study that will identify patients with known UIA seen in neurosurgery units. Patients will have baseline demographics and aneurysm characteristics collected by their neurosurgery unit and then a single aggregated national cohort will be linked to databases of hospital admissions and deaths to identify all patients who may have subsequently suffered a subarachnoid haemorrhage. All matched admissions and deaths will be checked against medical records to confirm the diagnosis of aneurysmal subarachnoid haemorrhage. The target sample size is 20 000 patients. The primary outcome will be aneurysm rupture resulting in hospital admission or death. Cox regression models will be built to test each of the study's aims. ETHICS AND DISSEMINATION: Ethical approval has been given by South Central Hampshire A Research Ethics Committee (21SC0064) and Confidentiality Advisory Group support (21CAG0033) provided under Section 251 of the NHS Act 2006. The results will be disseminated in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN17658526.

A comparison of odor plume-tracking behavior of walking and flying insects in different turbulent environments.

Many animals locate food, mates and territories by following plumes of attractive odors. There are clear differences in the structure of this plume-tracking behavior depending on whether an animal is flying, swimming, walking or crawling. These differences could arise from different control rules used by the central nervous system during these different modes of locomotion or one set of rules interacting with the different environments while walking on the surface versus flying or swimming. Flow speeds and turbulence that characterize the environments where walking and flying insects track plumes may alter the structure of odor plumes in an environment-specific way that results in the same control rules generating behaviors that appear quite different. We tested these ideas by challenging walking male cockroaches, Periplaneta americana, and flying male moths, Manduca sexta, to track plumes of their species' sex pheromones in low wind speeds characteristic of cockroach experimental environments, higher wind speeds characteristic of moth experimental environments, and conditions ranging from low to high turbulence. Introducing a turbulence-generating structure into the flow significantly improved the flying plume tracker's ability to locate the odor source, and changed the structure of the behavior of both flying and walking plume trackers. Our results support the idea that plume trackers moving slowly along the substrate may use the spatial distribution of odor, while faster moving flying plume trackers may use the timing of odor encounters to steer to locate the source.

Radiological follow-up of endovascularly treated intracranial aneurysms: a survey of current practice in the UK and Ireland.

PURPOSE: Due to the risk of intracranial aneurysm (IA) recurrence and the potential requirement for re-treatment following endovascular treatment (EVT), radiological follow-up of these aneurysms is necessary. There is little evidence to guide the duration and frequency of this follow-up. The aim of this study was to establish the current practice in neurosurgical units in the UK and Ireland. METHODS: A survey was designed with input from interventional neuroradiologists and neurosurgeons. Neurovascular consultants in each of the 30 neurosurgical units providing a neurovascular service in the UK and Ireland were contacted and asked to respond to questions regarding the follow-up practice for IA treated with EVT in their department. RESULTS: Responses were obtained from 28/30 (94%) of departments. There was evidence of wide variations in the duration and frequency of follow-up, with a minimum follow-up duration for ruptured IA that varied from 18 months in 5/28 (18%) units to 5 years in 11/28 (39%) of units. Young patient age, previous subarachnoid haemorrhage and incomplete IA occlusion were cited as factors that would prompt more intensive surveillance, although larger and broad-necked IA were not followed-up more closely in the majority of departments. CONCLUSIONS: There is a wide variation in the radiological follow-up of IA treated with EVT in the UK and Ireland. Further standardisation of this aspect of patient care is likely to be beneficial, but further evidence on the behaviour of IA following EVT is required in order to inform this process.

A survey of the radiological follow-up of unruptured intracranial aneurysms in the United Kingdom.

OBJECTIVE: Unruptured intracranial aneurysms (UIA) are common. For many the treatment risks outweigh their risk of subarachnoid haemorrhage and patients undergo surveillance imaging. There is little data to inform if and how to monitor UIAs resulting in widely varying practices. This study aimed to determine the current practice of unruptured UIA surveillance in the United Kingdom. METHODS: A questionnaire was designed to address the themes of surveillance protocols for UIA including when surveillance is initiated, how frequently it is performed, and when it is terminated. Additionally, how aneurysm growth is managed and how clinically meaningful growth is defined were explored. The questionnaire was distributed to members of the British Neurovascular Group using probability-based cluster and non-probability purposive sampling methods. RESULTS: Responses were received from 30 of the 30 (100.0%) adult neurosurgical units in the United Kingdom of which 27 (90.0%) routinely perform surveillance for aneurysm growth. Only four units had a unit policy. The mean patient age up to which a unit would initiate follow-up of a low-risk UIA was 65.4 ± 9.0 years. The time points at which imaging is performed varied widely. There was an even split between whether units use a fixed duration of follow-up or an age threshold for terminating surveillance. Forty percent of units will follow-up patients more than 5 years from diagnosis. The magnitude in the change in size that was felt to constitute growth ranged from 1 to 3mm. No units routinely used vessel wall imaging although 27 had access to 3T MRI capable of performing it. CONCLUSIONS: There is marked heterogeneity in surveillance practices between units in the United Kingdom. This study will help units better understand their practice relative to their peers and provide a framework forplanning further research on aneurysm growth.

Use of Self-Collected Saliva Samples for the Detection of SARS-CoV-2.

OBJECTIVE: Using a US Food and Drug Administration (FDA) emergency use authorization (EUA) reverse transcription polymerase chain reaction (RT-PCR) method, we examined the analytic performance accuracy of saliva specimens as compared to nasopharyngeal (NP) specimens in symptomatic patients. Correlation between test results and symptoms was also evaluated. METHODS: Over a 5-week period in 2020, 89 matched saliva and nasopharyngeal swabs were collected from individuals exhibiting symptoms consistent with SARS-CoV-2. Specimens were tested with an FDA EUA-approved RT-PCR method, and performance characteristics were compared. RESULTS: The concordance rate between saliva and nasopharyngeal testing was 93.26%. The mean cycle threshold value of saliva when compared to the NP specimen was 3.56 cycles higher. As compared to NP swab, saliva testing demonstrates acceptable agreement but lower sensitivity. CONCLUSION: When compared to a reference method using NP swabs, the use of saliva testing proved to be a reliable method. Self-collected saliva testing for SARS-CoV-2 allows for a viable option when trained staff or collection materials are in short supply.

Immune Activation in Primary Human Immunodeficiency Virus: Influence of Duration of Infection, Treatment, and Substance Use.

Background: Primary human immunodeficiency virus (HIV) is characterized by dynamic changes in viral load and innate and adaptive immune responses; it is unclear the extent to which time from acquisition to antiretroviral therapy (ART) initiation and substance use impact these immunologic changes. Methods: We studied plasma immune activation biomarkers, viral load, and CD4+ and CD8+ cell counts in participants from the Sabes primary infection study in Peru, who had been randomized to begin ART immediately after diagnosis vs 24 weeks later. We modeled influence of substance use and duration of HIV infection on biomarkers at baseline and over 24 weeks. Results: Compared to participants enrolled >30 days after HIV acquisition, participants enrolled during acute infection (≤30 days) had higher mean interferon (IFN)-γ and IFN-α2a (1.7-fold and 3.8-fold interquartile range [IQR] higher, respectively). Participants enrolled >30 days after HIV acquisition had higher mean baseline CD8+ cell count (2.7 times the IQR). Alcohol use (positive phosphatidylethanol level) was associated with elevated IFN-γ, tumor necrosis factor alpha (TNF-α), and interleukin 12p70 (IL-12p70), and smoking was associated with higher macrophage inflammatory protein 1α, TNF-α, and IL-12p70. Most biomarkers declined more quickly in participants who initiated ART immediately; however, substance use and duration of HIV infection at enrollment had little influence on rate of decline. Conclusions: IFN-γ and other biomarkers are elevated during early primary infection, when exposure to HIV antigens is high. Immune activation decreased most quickly in those who started ART during acute/early primary infection. Higher CD8+ cell counts and a trend toward higher soluble CD163 levels during the 30 days after acquisition suggest the onset of compensatory responses and immune exhaustion.

Obstructive hydrocephalus secondary to a perianeurysmal cyst: a case report.

Perianeurysmal cysts are an extremely rare association with cerebral aneurysms. We report the case of a 64 year old male who presented with obstructive hydrocephalus due to a perianeurysmal cyst. The cyst originated in association with a thrombosed, right-sided, terminal internal carotid artery aneurysm. Definitive management was offered with craniotomy and surgical clipping of the aneurysm together with endoscopic cyst fenestration. The patient made a full recovery and was asymptomatic at 3-month follow-up. We review the literature and discuss the potential mechanisms of cyst formation.

Linkage to care after HIV diagnosis among men who have sex with men and transgender women in Lima, Peru.

In Lima, Perú, HIV prevalence is estimated to be 15% among men who have sex with men (MSM) and 30% among transgender women (TW). We investigated timely linkage of MSM and TW to HIV care, as linkage to antiretroviral therapy (ART) is critical to protect the health of those living with HIV and to prevent onward transmission. We investigated linkage within 90 days of HIV diagnosis by matching data from two studies conducted in Lima between 2013 and 2015 to national ART program records. We used generalized linear modeling to assess predictors of timely linkage and late presentation to care. Of 487 newly-diagnosed MSM and TW, only 44% presented for care at an HIV clinic within 90 days. Timely linkage was less common among TW (aPR 0.7, 95% CI 0.5-1.0), those younger than 24 (aPR 0.8, 95% CI 0.6-1.0), and those reporting a history of sex work (aPR 0.7, 95% CI 0.6-0.9). Proximity to an ART program clinic was not associated with linkage; most participants linked to clinics offering "LGBTQ-friendly" care. The pattern of clinics selected by participants suggests the importance of concerns about confidentiality and stigma in decision-making about where to link to care.

Performance Accuracy of a Laboratory-Developed Real-Time RT-PCR Method for Detection of SARS-CoV-2 in Self-Collected Saliva Specimens.

OBJECTIVE: The ongoing COVID-19 pandemic caused by SARS-CoV-2 has challenged diagnostic laboratories to re-examine traditional methods for collecting specimens and sample types used in molecular testing. Our goal was to demonstrate that saliva can be used for detecting SARS-CoV-2 and correlates well with established molecular methods using nasopharyngeal (NP) swabs. METHODS: We examined use of a saliva collection device in conjunction with a laboratory-developed real-time reverse transcription-polymerase chain reaction (LDPCR) method for detecting SARS-CoV-2 in a symptomatic population and compared results with 2 US Food and Drug Administration (FDA)-approved methods (emergency use authorization [EUA]) that use specimens from NP swabs. RESULTS: The sensitivity of LDPCR compared with the reference methods was 75.0% (21/28); specificity, 98.1% (104/106). When cycle threshold values were compared between paired specimens using the LDPCR and a EUA reverse transcription PCR method, both targeting the open-reading frame gene, the mean value for saliva was 4.66 cycles higher than for NP specimens. CONCLUSION: Use of self-collected saliva in conjunction with an LDPCR for SARS-CoV-2 compared favorably with 2 FDA EUA methods using NP swabs. The use of an alternative sample type and assay method will aid in expanding the availability of testing during the ongoing COVID-19 pandemic.

Defect-Free Single-Layer Graphene by 10 s Microwave Solid Exfoliation and Its Application for Catalytic Water Splitting.

Mass production of defect-free single-layer graphene flakes (SLGFs) by a cost-effective approach is still very challenging. Here, we report such single-layer graphene flakes (SLGFs) (>90%) prepared by a nondestructive, energy-efficient, and easy up-scalable physical approach. These high-quality graphene flakes are attributed to a novel 10 s microwave-modulated solid-state approach, which not only fast exfoliates graphite in air but also self-heals the surface of graphite to remove the impurities. The fabricated high-quality graphene films (∼200 nm) exhibit a sheet resistance of ∼280 Ω/sq without any chemical or physical post-treatment. Furthermore, graphene-incorporated Ni-Fe electrodes represent a remarkable ∼140 mA/cm2 current for the catalytic water oxidation reaction compared with the pristine Ni-Fe electrode (∼10 mA/cm2) and a 120 mV cathodic shift in onset potential under identical experimental conditions, together with a faradic efficiency of >90% for an ideal ratio of H2 and O2 production from water. All these excellent performances are attributed to extremely high conductivity of the defect-free graphene flakes.

The role of Facebook groups in the management and raising of awareness of antidepressant withdrawal: is social media filling the void left by health services?

BACKGROUND: Antidepressant withdrawal is experienced by about half of people who try to reduce or come off their medication. It can be a debilitating, long lasting process. Many clinicians misdiagnose or minimise symptoms, inadvertently prolonging suffering. Most are unable to help patients safely taper off. There has been little research into the peer support communities that are playing an increasingly important role in helping people withdraw from psychiatric medications. METHODS: To illustrate the growth and activities of Facebook withdrawal groups, we examined 13 such groups. All were raising awareness of, and supporting individuals tapering off, antidepressants and were followed for 13 months. A further three groups were added for the last 5 months of the study. RESULTS: In June 2020, the groups had a total membership of 67,125, of which, 60,261 were in private groups. The increase in membership for the 13 groups over the study period was 28.4%. One group was examined in greater detail. Group membership was 82.5% female, as were 80% of the Administrators and Moderators, all of whom are lay volunteers. Membership was international but dominated (51.2%) by the United States (US). The most common reason for seeking out this group was failed clinician-led tapers. DISCUSSION: The results are discussed in the context of research on the prevalence, duration and severity of antidepressant withdrawal. We question why so many patients seek help in peer-led Facebook groups, rather than relying on the clinicians that prescribed the medications. The withdrawal experiences of tens of thousands of people remain hidden in these groups where they receive support to taper when healthcare services should be responsible. Further research should focus on the methods of support and tapering protocols used in these groups to enable improved, more informed support by clinicians. Support from Governments and healthcare agencies is also needed, internationally, to address this issue.

Sexual Behavior Among Men Who Have Sex With Men: The Need for More Targeted Outreach to Men Who Also Have Sex With Cisgender Women.

BACKGROUND: In Peru, as in the Americas overall, men who have sex with men (MSM) are disproportionately affected by HIV. Most research focuses on practices between cisgender men, whereas many MSM report male and female partners, cisgender, transgender, or both. METHODS: Data for these analyses were from a treatment-as-prevention study in Lima (the Sabes study). We compared demographics and behaviors of MSM who reported cisgender women partners in the past 3 months (MSMW) and MSM who reported both cisgender and transgender women partners (MSMW-T) to MSM who reported only male partners (MSMO). We calculated HIV incidence in each group during 2-year follow-up. RESULTS: Compared with MSMO, MSMW and MSMW-T more often self-identify as heterosexual or bisexual and report insertive sex practices. MSMW reported condomless sex with cisgender women: vaginal (72%), anal sex (18%). One-third of MSMW reported condomless receptive anal sex with men in the past 3 months, with 24% of MSMW overall who reported both condomless receptive sex with men and condomless insertive vaginal or anal sex with cisgender women. Of these, 17% were HIV infected. HIV incidence did not differ significantly between groups. CONCLUSION: Most MSMW and MSMW-T report bisexual or heterosexual orientation and prefer insertive sex. MSMW and MSMW-T (47% and 29%, respectively) engage in receptive anal intercourse. In both groups, the majority who engaged in condomless receptive sex with men (76% MSMW, 85% MSMW-T) also engaged in condomless vaginal and/or anal sex with women, indicating need for intervention.

Safety of oral naltrexone in HIV-positive men who have sex with men and transgender women with alcohol use disorder and initiating antiretroviral therapy.

HIV disproportionately affects men who have sex with men (MSM) and transgender women (TW). These populations use alcohol more heavily than the general population, and alcohol use disorders (AUDs) are more prevalent among them. Naltrexone (NTX) has documented efficacy and safety as a medication-assisted therapy for AUD. Its use has not been well-examined in persons with HIV (PWH) newly initiating antiretroviral therapy (ART) where the possibility of hepatotoxicity may be increased when initating multiple new medications. This study assessed the safety of oral NTX treatment (50 mg daily) initiated concomitantly with antiretroviral therapy (ART) in a double-blind randomized placebo-controlled trial of NTX in MSM/TW in Lima, Peru among MSM and TW with AUD (AUDIT score ≥ 8). We analyzed adverse event data from ART-naïve participants (N = 155) who were randomized (2:1) to initiate ART plus NTX (N = 103) or ART plus placebo (N = 52). Participants were monitored for 24 weeks while taking ART plus NTX/placebo, followed by 24 weeks receiving ART alone. Over 48 weeks, 135 grade 2 or 3 adverse events were reported, resulting in 1.3 clinical adverse events per participant equally represented in both treatment and placebo arms. Two serious adverse events occurred among two participants receiving NTX; neither was attributed to the study medication. No significant differences were found in the proportion of subjects reporting any adverse events between treatment arms across all time-points. These results suggest NTX is safe in MSM/TW PWH with AUD newly initiating ART, as no excess of clinical adverse events or transaminase elevation was associated with NTX use.

Development of the Melanoma Concerns Questionnaire (MCQ-28); refinement of the EORTC QLQ-MEL38 module.

OBJECTIVE: Few patient-reported outcome measures (PROMs) have been developed that adequately measure the patient-experience following diagnosis and treatment of melanoma. Building on previous research, which developed the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Module (QLQ-MEL38), the aim of this study was to further test the hypothesised domain structure and psychometric properties of the phase 3 module, in a new larger sample of melanoma patients. METHODS: Melanoma patients (n = 270) were recruited from four countries (Australia, England, Serbia, and Spain). Patients completed the EORTC core questionnaire (QLQ-C30), the QLQ-MEL38, and a sociodemographic survey. Using this new larger dataset, comparisons were made with the hypothesised domain structure of the EORTC phase 3 module using principal component analysis. Items which formed subscales in a revised domain structure were then tested for goodness of fit (GoF) to the Rasch model. RESULTS: The original hypothesised and final domain structures were similar but not identical. Twenty-four items (83%) loaded onto the same distinct subscales previously generated by phase 3, and item-by-item comparison of the two pattern matrices indicated an extremely close match. Ten items were removed from the QLQ-MEL38 phase 3 module, and rescoring of some items was required. Four subscales, together with five individual items, comprised the final instrument. CONCLUSION: The newly developed measure (named the Melanoma Concerns Questionnaire; MCQ-28) was found to tap into several important psychosocial domains of concern to melanoma patients, particularly those being managed in "usual" clinic settings.

Characterizing Men Who Have Sex with Transgender Women in Lima, Peru: Sexual Behavior and Partnership Profiles.

HIV prevalence is high among transgender women (TW), but how HIV is transmitted to this population is not well understood. This analysis aims to characterize sexual partners of TW (PTW) to understand how their behavior contributes to HIV risk among TW. We examined baseline data from TW, PTW, and men who have sex with men (MSM) from a treatment-as-prevention study in Lima, Peru. Individual and partnership characteristics were compared across groups, and Poisson regression was used to calculate prevalence ratios for associations between sexual concurrency and potential correlates. We found that 81% of PTW had no cisgender male partners. Prevalence of alcohol dependency, concurrency, and condomless anal intercourse was high and HIV testing was low compared to the other groups. Our results suggest that PTW are a distinct population from MSM and TW, engage in behavior associated with HIV transmission, and are likely not well reached by HIV prevention interventions.

Mapping the Origins of Luminescence in ZnO Nanowires by STEM-CL.

In semiconductor nanowires, understanding both the sources of luminescence (excitonic recombination, defects, etc.) and the distribution of luminescent centers (be they uniformly distributed, or concentrated at structural defects or at the surface) is important for synthesis and applications. We develop scanning transmission electron microscopy-cathodoluminescence (STEM-CL) measurements, allowing the structure and cathodoluminescence (CL) of single ZnO nanowires to be mapped at high resolution. Using a CL pixel resolution of 10 nm, variations of the CL spectra within such nanowires in the direction perpendicular to the nanowire growth axis are identified for the first time. By comparing the local CL spectra with the bulk photoluminescence spectra, the CL spectral features are assigned to internal and surface defect structures. Hyperspectral CL maps are deconvolved to enable characteristic spectral features to be spatially correlated with structural features within single nanowires. We have used these maps to show that the spatial distribution of these defects correlates well with regions that show an increased rate of nonradiative transitions.

Fast Exfoliation and Functionalisation of Two-Dimensional Crystalline Carbon Nitride by Framework Charging.

Two-dimensional (2D) layered graphitic carbon nitride (gCN) nanosheets offer intriguing electronic and chemical properties. However, the exfoliation and functionalisation of gCN for specific applications remain challenging. We report a scalable one-pot reductive method to produce solutions of single- and few-layer 2D gCN nanosheets with excellent stability in a high mass yield (35 %) from polytriazine imide. High-resolution imaging confirmed the intact crystalline structure and identified an AB stacking for gCN layers. The charge allows deliberate organic functionalisation of dissolved gCN, providing a general route to adjust their properties.

Preparation of Ibuprofen Microparticles by Antisolvent Precipitation Crystallization Technique: Characterization, Formulation, and In Vitro Performance.

This study demonstrates the preparation and characterization of ibuprofen (IBP) microparticles with some excipients by a controlled crystallization technique with improved dissolution performance. Using the optimum concentrations pluronic F127, hydroxypropyl methyl cellulose, D-mannitol, and l-leucine in aqueous ethanol, the IBP microparticles were prepared. The dissolution tests were performed in phosphate buffer saline using a United States Pharmacopoeia dissolution tester at 37°C. The Raman spectroscopy was used to investigate the interactions and distribution of the IBP with the additives in the microcrystals. The prepared IBP microparticles showed higher dissolution compared to that of the smaller sized original IBP particles. The Raman data revealed that the excipients with a large number of hydroxyl groups distributed around the IBP particle in the crystal enhanced the dissolution of the drug by increasing the drug-solvent interaction presumably through hydrogen bonding. The Raman mapping technique gave an insight into the enhanced dissolution behavior of the prepared IBP microparticles, and such information will be useful for developing pharmaceutical formulations of hydrophobic drugs. The controlled crystallization was a useful technique to prepare complex crystals of IBP microparticles along with other additives to achieve the enhanced dissolution profile.

Laser Sintering of Liquid Metal Nanoparticles for Scalable Manufacturing of Soft and Flexible Electronics.

Soft, flexible, and stretchable electronics are needed to transmit power and information, and track dynamic poses in next-generation wearables, soft robots, and biocompatible devices. Liquid metal has emerged as a promising material for these applications due to its high conductivity and liquid phase state at room temperature; however, surface oxidation of liquid metal gives it unique behaviors that are often incompatible with scalable manufacturing techniques. This paper reports a rapid and scalable approach to fabricate soft and flexible electronics composed of liquid metal. Compared to other liquid metal patterning approaches, this approach has the advantages of compatibility with a variety of substrates, ease of scalability, and efficiency through automated processes. Nonconductive liquid metal nanoparticle films are sintered into electrically conductive patterns by use of a focused laser beam to rupture and ablate particle oxide shells, and allow their liquid metal cores to escape and coalesce. The laser sintering phenomenon is investigated through comparison with focused ion beam sintering and by studying the effects of thermal propagation in sintered films. The effects of laser fluence, nanoparticle size, film thickness, and substrate material on resistance of the sintered films are evaluated. Several devices are fabricated to demonstrate the electrical stability of laser-patterned liquid metal traces under flexing, multilayer circuits, and intricately patterned circuits. This work merges the precision, consistency, and speed of laser manufacturing with the material benefits of liquid conductors on elastic substrates to demonstrate decisive progress toward commercial-scale manufacturing of soft electronics.