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Despite intracerebral haemorrhage causing 5% of deaths worldwide, few evidence-based therapeutic strategies other than stroke unit care exist. Tranexamic acid decreases haemorrhage in conditions such as acute trauma and menorrhoea. We aimed to assess whether tranexamic acid reduces intracerebral haemorrhage growth in patients with acute intracerebral haemorrhage.We did a prospective, double-blind, randomised, placebo-controlled, investigator-led, phase 2 trial at 13 stroke centres in Australia, Finland, and Taiwan. Patients were eligible if they were aged 18 years or older, had an acute intracerebral haemorrhage fulfilling clinical criteria (eg, Glasgow Coma Scale score of7, intracerebral haemorrhage volume70 mL, no identified or suspected secondary cause of intracerebral haemorrhage, no thrombotic events within the previous 12 months, no planned surgery in the next 24 h, and no use of anticoagulation), had contrast extravasation on CT angiography (the so-called spot sign), and were treatable within 4·5 h of symptom onset and within 1 h of CT angiography. Patients were randomly assigned (1:1) to receive either 1 g of intravenous tranexamic acid over 10 min followed by 1 g over 8 h or matching placebo, started within 4·5 h of symptom onset. Randomisation was done using a centralised web-based procedure with randomly permuted blocks of varying size. All patients, investigators, and staff involved in patient management were masked to treatment. The primary outcome was intracerebral haemorrhage growth (33% relative or6 mL absolute) at 24 h. The primary and safety analyses were done in the intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT01702636).Between March 1, 2013, and Aug 13, 2019, we enrolled and randomly assigned 100 participants to the tranexamic acid group (n=50) or the placebo group (n=50). Median age was 71 years (IQR 57-79) and median intracerebral haemorrhage volume was 14·6 mL (7·9-32·7) at baseline. The primary outcome was not different between the two groups: 26 (52%) patients in the placebo group and 22 (44%) in the tranexamic acid group had intracerebral haemorrhage growth (odds ratio [OR] 0·72 [95% CI 0·32-1·59], p=0·41). There was no evidence of a difference in the proportions of patients who died or had thromboembolic complications between the groups: eight (16%) in the placebo group vs 13 (26%) in the tranexamic acid group died and two (4%) vs one (2%) had thromboembolic complications. None of the deaths was considered related to study medication.Our study does not provide evidence that tranexamic acid prevents intracerebral haemorrhage growth, although the treatment was safe with no increase in thromboembolic complications. Larger trials of tranexamic acid, with simpler recruitment methods and an earlier treatment window, are justified.National Health and Medical Research Council, Royal Melbourne Hospital Foundation.

Introduction: Despite pharmacological and practical advantages for tenecteplase (TNK) over alteplase (ALT), no differences were observed in percent of symptomatic intracranial hemorrhage (sICH) in randomized trials (fewer than 900 total patients for either treatment). We compared rates of sICH in patients treated with either drug, using a large, multicenter, international registry. Methods: The CERTAIN collaboration is an ongoing registry of deidentified patient-level data of thrombolytic treated ischemic stroke from various hospitals/programs in New Zealand, Australia, and the United States that have used ALT or TNK since July 1, 2018. Standardized data were abstracted and harmonized from local or regional clinical registries. We defined sICH as clinical worsening of at least 4 points on NIHSS, attributed to parenchymal hematoma, subarachnoid or intraventricular hemorrhage. We used logistic regression for binary variables, adjusting sICH differences for age, baseline NIHSS, thrombectomy, and source hospital network and Mann-Whitney test for continuous baseline variables. Results: A total of 7891 patients were included in the initial analysis. The TNK group was older, more likely to be male, had higher NIHSS, and more frequently underwent mechanical thrombectomy (Table. Sample Characteristics). The sICH rate was 3.71% for ALT and 2.13% for TNK: adjusted OR (95%CI) = 0.49 (0.31-0.76) p=0.002. For patients not undergoing thrombectomy after thrombolytic, the sICH rate was 3.00% for ALT and 1.74% for TNK, adjusted OR (95%CI) = 0.48 (0.27-0.87), p=0.016. For thrombectomy treated cases, sICH rate was 6.80% for ALT and 2.80% for TNK, adjusted OR (95%CI) 0.60 (0.31-1.16), p=0.129. Conclusion: In this preliminary analysis from a large, multicenter registry, ischemic stroke treated with tenecteplase was associated with a lower rate of sICH than with alteplase. An updated analysis with patient data from additional sites will be presented at the Conference.

A young woman with a history of previously undiagnosed episodic neurological deterioration since early childhood associated with viral illnesses developed fulminant encephalitis. Standard investigations gave no diagnosis. Next-generation sequencing identified a heterozygous mutation c.1754C>T (p.Thr585Met) in the RANBP2 gene, giving the diagnosis of recurrent acute necrotising encephalopathy type 1. This condition is probably underdiagnosed, especially in adults, and should be considered in patients with recurrent encephalopathy.

Implantable optical nanosensors hold the promise of rapid, minimally-invasive longitudal monitoring of analytes in a patient or animal. Such devices will allow for informed clinical intervention based on changes in drug, biomarker, or disease state profiles. We developed implantable nanosensors based on the optical properties of single-walled carbon nanotubes (SWCNT). SWCNT fluorescence is in the ‘tissue-transparent’ near-infrared spectrum, allowing for fluorescence measurements after implantation inside an animal. Further, SWCNT fluorescence is photostable, allowing for multiple measurements over time. We engineered separate SWCNT-based sensors such that their fluorescence emission responded to various analytes, including small molecule drugs as well as protein and nucleic acid biomarkers. Each sensor device was immobilized into a semi-permeable biocompatible membrane, allowing analyte penetration but retaining SWCNT inside. We implanted each sensor device into live mice, either in the peritoneal cavity or subcutaneously, and performed whole-mouse near-infrared fluorescence imaging to ensure the stability of the membrane and sensor brightness. We used a sensor implant specific for the chemotherapeutic doxorubicin to drug monitor transport within the animal. We used sensor implants specific for the ovarian cancer protein biomarker HE4 or for individual microRNA sequences to measure exogenous or cancer-generated quantities of each biomarker in mice. We expect these implantable sensors to have potential as research tools or clinical diagnostics to monitor pharmacokinetics or locally measure disease biomarkers in real-time.

A young woman with a history of previously undiagnosed episodic neurological deterioration since early childhood associated with viral illnesses developed fulminant encephalitis. Standard investigations gave no diagnosis. Next-generation sequencing identified a heterozygous mutation c.1754CT (p.Thr585Met) in the

Modulation of the carbon nanotube photoluminescence band position has implications for applications such as sensing and imaging. Carbon nanotube photoluminescence solvatochromism, the hypsochromic or bathochromic shifting of nanotube emission, can be induced via changes in the local dielectric environment. We developed methods to modulate nanotube solvatochromic behavior to improve sensor responses, and we developed tools to observe solvatochromism within live cells and, recently, live animals. We found that nanotube solvatochromism extends to variations of local electrostatic charge, induced by adsorption/desorption of polyelectrolytes on the nanotube surface, such as proteins and nucleic acids. We also found that dielectric and charge-mediated solvatochromism can be compounded to exacerbate the response. Upon triggered desorption of a polyelectrolyte, such as upon desorption of RNA upon hybridization, for instance, amphiphilic molecules can adsorb to the recently-uncovered nanotube surface. The adsorption displaces water to result in hypsochromic shifting, which can be additive, as polyelectrolyte desorption will also cause a hypsochromic shift. We found that the amphiphile may be a surfactant but, recently, we found that proteins can result in a similar response, facilitating the detection of viruses. We developed tools to image changes in nanotube emission in live cells (near-infrared hyperspectral microscopy) and, recently, live animals (preclinical, near-infrared hyperspectral imaging). Carbon nanotube solvatochromism-based sensors, in combination with spectral imaging tools, allow measurements of biomarkers, drugs, and metabolites in live cells and organisms, facilitating improvements in disease detection, drug development, and biomedical research.

Carbon nanomaterials have unique structural and optical properties that have been under-explored for the development of artistic applications. We developed pigments and fluorescent dyes using single-walled carbon nanotube and graphene to create visual art. We developed carbon nanotube-based pigments for application to paper and other solid substrates with optimal fluorescence in the infrared. The photoluminescence of these paints was used to generate artwork that illuminates the unique properties and opportunities inherent in the material. We developed several methods to visualize the near-infrared nanotube emission, including novel lighting solutions as well as imaging solutions, for use with large-scale visual art formats. We also developed large-scale visual art using graphene as a pigment. Laser-induced graphene was synthesized in-situ on paper substrates with dimensions up to 20 x 30 inches. Machine-automated processes allowed the faithful reproduction of computer-generated artwork into graphene on an “artist’s canvas.”

The early detection of cancer could lead to vastly improved patient outcomes. We aim to identify cancer biomarkers within the body at early disease stages, permitting detection before symptoms arise. We are developing implantable nanosensors, using the unique optical properties of carbon nanotubes, to facilitate non-invasive detection via optical detection through living tissues. The sensors could enable early detection of cancer in people at high risk for the disease, in successfully treated patients to monitor recurrence, or in patients who are undergoing treatment to inform clinical decisions.

The detection of biomarkers and drugs in live cells and animals would allow for more effective studies of the dynamics of cancer and treatment. Toward these ends, single-walled carbon nanotube photoluminescence is suitable for measurements in live cells and in vivo, and nanotube near-infrared emission exhibits sensitivity to the local environment via solvatochromic responses. We developed new optical instrumentation to image carbon nanotubes and to measure spectral changes of carbon nanotube photoluminescence in live cells and animals. Concomitantly, we developed new methods to exacerbate the nanotube emission response to produce large spectral shifts (> 14 nm) upon the binding of cancer biomarkers and chemotherapeutic drugs. The ability to improve measurements and control of carbon nanotube solvatochromism may improve sensitivity and selectivity of nanosensors and potentially expand the application of nanotube-based optical measurements to new classes of bioanalytes.

The unique optical properties of single-walled carbon nanotubes (SWCNT) confer ideal sensing properties for biological applications. SWCNT near-infrared photoluminescence exhibits photostability, penetration through biological media, and environmental sensitivity. Nanotube emission can undergo modulation of the optical bandgap, causing a shift in emission wavelength. These characteristics allow for consistent rapid and long-term analyte detection and quantification in complex ex vivo and in vivo environments. We have employed these unique properties to develop biomarker-specific SWCNT-based sensors for translational biomedical applications.