Jack Hellerstedt

Two‐dimensional (2D) materials with frustrated crystal geometries can host strongly correlated electrons, potentially leading to a range of exotic many‐body quantum phases, such as Mott insulators, quantum spin‐liquids, and Kondo lattices. The ability to control exchange‐coupling within these systems is therefore highly desirable. Here, we use an atomically sharp scanning tunneling microscope probe to vertically manipulate a 2D Mott insulating honeycomb‐kagome metal‐organic framework (MOF) featuring Kondo‐screened local magnetic moments on Ag(111). We show that by controlling the adsorption height of the MOF, we can also controllably and reversibly change the strength of Kondo coupling between the MOF's local spins and the substrate's conduction electrons. This mechanical control of Kondo coupling could be extended to other forms of interlayer exchange coupling, potentially allowing for atomic‐scale design or control of spintronics technologies.

IMPORTANCE: Point-of-care, non-invasive brain monitoring in critically ill patients following cardiac arrest could provide earlier detection of neurological injury and, when combined with earlier treatments, limit brain injury. Point-of-care monitoring could also enable better neuro-prognostication. OBJECTIVES: The study assessed the time to detection of brain injury using optical brain pulse monitoring (OBPM) compared to routine brain monitoring. The association of OBPM signals with more severe forms of brain injury was also assessed. DESIGN: Retrospective analysis of patients enrolled in an observational study. SETTING: Critical care unit of a tertiary academic hospital. PARTICIPANTS: Adult patients requiring mechanical ventilation in a critical care unit following a cardiac arrest. MAIN OUTCOMES AND MEASURES: OBPM uses red and infrared light to capture brain pulse waveforms whose morphology reflects the relative arteriole and venous pressure levels driving microvascular blood flow in the brain. The OBPM sensors were placed bilaterally on the anterior temporal region of the scalp, over the middle cerebral artery territories. Time to brain injury detection was defined as the period from cardiac arrest to the first detection of brain injury by OBPM or routine monitoring. RESULTS: Twelve patients were enrolled, three required veno-arterial extra-corporeal membrane oxygenator support. In-hospital mortality was 83% and eight patients developed global hypoxic-ischemic brain injury. The median time to detection of brain injury was 57 hours earlier using OBPM compared to routine monitoring (P < 0.01). In brain injured patients OBPM brain pulse morphologies changed over time and were often different between hemispheres, high amplitude respiratory waves were also present. Known poor prognostic brain pulse waveform morphologies were present in some patients with severe brain injury. CONCLUSIONS AND RELEVANCE: OBPM detected brain injury earlier compared to routine brain monitoring. Earlier detection of neurological injury could improve patient outcomes through earlier treatment and better neuro-prognostication. KEY POINTS: Question: Can point-of-care non-invasive optical brain pulse monitoring (OBPM) in critically ill patients following cardiac arrest provide earlier detection of brain injury compared to routine monitoring? Findings: In this observational study of 12 patients the median time to detection of brain injury was 57 hours earlier using OBPM compared to routine monitoring. Meaning: Earlier detection of brain injury could improve patient outcomes through earlier treatment and better neuro-prognostication.

Early stroke detection and treatment are critical for improving patient outcomes. Optical brain pulse monitoring (OBPM) uses red and infrared light to capture brain pulse waveforms reflecting arteriole-to-venous pressure levels driving microvascular blood flow. This study assessed OBPM’s potential to detect middle cerebral artery occlusion (MCAo) and reperfusion in a clinically relevant sheep model. Stroke was induced in 11 Merino wethers via 4-hour occlusion of the right MCA, followed by 6 hours of reperfusion. OBPM recordings were taken at baseline, MCAo, early and late reperfusion. The OBPM brain pulse waveform classes were classified based on the presence of arterial or central venous circulation wave features. Magnetic resonance imaging assessed infarct volume at 2 hours post-reperfusion. Invasive brain tissue oxygen and intracranial pressures were also monitored. The OBPM brain pulse waveform classes changed during MCAo and reperfusion ( p p = 0.0007). Reperfusion was associated with the return of arterial circulation features ( p = 0.001). Early reperfusion was also associated with an increase in the brain pulse amplitude ( p < 0.05) and the respiratory wave amplitude ( p < 0.05). OBPM may aid in early stroke detection and reperfusion assessment following intervention.

Early detection of neurological deterioration in serious acute brain injury is seen as an important goal to reduce death and disability, but monitoring for neurological deterioration remains challenging. Routine methods, such as neurological examination and brain imaging, often identify brain injuries only after they have progressed to an irreversible stage. Alternate approaches such as invasive brain monitoring, are complex, costly and carry inherent risks. The optical brain pulse monitor (OBPM) is a novel, noninvasive, safe, and continuous monitoring device designed to provide earlier detection of neurological deterioration and address the limitations of traditional approaches. This review presents the development, technical aspects, and clinical results from past and ongoing trials over the last five years.

Scanning Tunnelling Microscopes (STM) are capable of capturing images of surfaces with atomic-scale resolution. This is achieved by scanning an atomically sharp probe across the surface of the sample while monitoring an electric current. However, the quality of STM data relies heavily on the atomic-scale geometry and composition of the scanning probe apex, as well as the roughness and cleanliness of the scanned region. For instance, blunt tips result in blurry images while contaminated tips can lead to noisy images due to interactions with the sample. As a result, optimal STM data acquisition commonly requires time-consuming tasks such as probe conditioning-i.e., sharpening via "tip-shaping", where the apex of the probe can be refined by poking it into a clean metal surface-and identification of areas of interest of the sample. Moreover, the quality of the probe can vary during a scan, especially when scanning over debris or excessively rough areas, necessitating additional tip-shaping.

Electron-electron interactions in materials lead to exotic many-body quantum phenomena, including Mott metal-insulator transitions (MITs), magnetism, quantum spin liquids, and superconductivity. These phases depend on electronic band occupation and can be controlled via the chemical potential. Flat bands in two-dimensional (2D) and layered materials with a kagome lattice enhance electronic correlations. Although theoretically predicted, correlated-electron Mott insulating phases in monolayer 2D metal-organic frameworks (MOFs) with a kagome structure have not yet been realised experimentally. Here, we synthesise a 2D kagome MOF on a 2D insulator. Scanning tunnelling microscopy (STM) and spectroscopy reveal a MOF electronic energy gap of ∼200 meV, consistent with dynamical mean-field theory predictions of a Mott insulator. Combining template-induced (via work function variations of the substrate) and STM probe-induced gating, we locally tune the electron population of the MOF kagome bands and induce Mott MITs. These findings enable technologies based on electrostatic control of many-body quantum phases in 2D MOFs.

Subarachnoid haemorrhage (SAH) can trigger a range of poorly understood cerebrovascular responses that may play a role in delayed cerebral ischemia. The brain pulse monitor is a novel non-invasive device that detects a brain photoplethysmography signal that provides information on intracranial pressure (ICP), compliance, blood flow and tissue oxygen saturation. We monitored the cerebrovascular responses in a patient with Lundberg B waves following a SAH. The patient presented with a Fischer grade 4 SAH that required urgent left posterior communicating artery aneurysm coiling and ventricular drain insertion. On hospital day 4 oscillations or spikes on the invasive ICP were noted, consistent with Lundberg B waves. Brain pulse monitoring demonstrated concurrent pulse waveform features consistent with reduced brain compliance and raised ICP over both brain hemispheres. Oxygen levels also demonstrated slow oscillations correlated with the ICP spikes. Brief infrequent episodes of reduced and absent brain pulses were also noted over the right hemisphere. Our findings suggest that the brain pulse monitor holds promise for early detection of delayed cerebral ischemia and could offer insights into the vascular mechanisms at play. Plain Language Summary: In this study, we examined a patient with a serious brain bleed, known as subarachnoid hemorrhage (SAH). Patients with SAH can suffer from vasospasm and consequent delayed cerebral ischemia (DCI), which can happen from 4 to 14 days after the initial bleeding. Detecting and treating DCI early is difficult because methods are imperfect, discontinuous and technically difficult. We used a new, non-invasive device that can monitor various features of brain health. This device helps us understand the pressure inside the skull, blood flow, and the oxygen saturation on the surface of the brain. In this patient, we found evidence of:Brain pulse signals that were directly related to acute changes in the invasive intracranial pressure.Specific brain pulse patterns that may indicate a local reduction in brain blood flow.Signs of a breakdown in the brain’s ability to regulate blood flow in the injured hemisphere.The oxygen saturation levels in the brain that related to pressure changes. These results are promising because they suggest the new device could help us identify when someone’s brain condition is getting worse. This ability could guide the development of improved care protocols, and aid clinical decision-making. Further research is needed in this patient population with additional forms of monitoring to understand the generalizability of our findings.

Two-dimensional (2D) nanostructures and nanomaterials offer potential for a wide range of technological applications in electronics, optoelectronics, data storage, sensing and catalysis. On-surface molecular self-assembly – where organic molecules act as building blocks and where surfaces play the role of supporting templates – allows for the bottom-up synthesis of such 2D systems with tuneable atomically precise morphologies and tailored electronic properties. These self-assembly protocols are well established on metal surfaces, but remain limited on electronically gapped substrates (insulators, semiconductors). The latter are useful for preventing electronic coupling (that is, hybridization between molecular assembly and underlying surface) and for avoiding quenching of optical processes, necessary for prospective electronic and optoelectronic applications. In particular, molecular self-assembly on surfaces other than weakly interacting metals can be challenging due to substrate reactivity, defects and inhomogeneities, resulting in intricate energy landscapes that limit the growth kinetically and hampers the synthesis of large-area defect-free 2D systems. Here, we demonstrate the self-assembly of a 2D, atomically thin organic molecular film on a model wide bandgap 2D insulator, single-layer hexagonal boron nitride (hBN) on Cu(111). The molecular film consists of flat, aromatic 9,10-di-cyano-anthracene (DCA) molecules. Our low-temperature scanning tunnelling microscopy and spectroscopy measurements revealed mesoscopic (> 100 x 100 nm^2), topographically homogeneous crystalline molecular domains resulting from flat molecular adsorption and noncovalent in-plane cyano-ring bonding, with electronically decoupled molecular orbitals (MOs) lying within the hBN electronic gap. These MOs exhibit an energy level spatial modulation (~300 meV) that follows the moiré work function variation of hBN on Cu(111). This work paves the way for large-area, atomically precise, highly crystalline 2D organic (and metal-organic) nanomaterials on electronically functional wide bandgap insulators.

Background: Intracranial pressure (ICP) monitoring requires placing a hole in the skull through which an invasive pressure monitor is inserted into the brain. This approach has risks for the patient and is expensive. We have developed a non-invasive brain pulse monitor that uses red light to detect a photoplethysmographic (PPG) signal arising from the blood vessels on the brain’s cortical surface. The brain PPG and the invasive ICP waveform share morphological features which may allow measurement of the intracranial pressure. Methods: We enrolled critically ill patients with an acute brain injury with invasive ICP monitoring to assess the new monitor. A total of 24 simultaneous invasive ICP and brain pulse monitor PPG measurements were undertaken in 12 patients over a range of ICP levels. Results: The waveform morphologies were similar for the invasive ICP and brain pulse monitor PPG approach. Both methods demonstrated a progressive increase in the amplitude of P2 relative to P1 with increasing ICP levels. An automated algorithm was developed to assess the PPG morphological features in relation to the ICP level. A correlation was demonstrated between the brain pulse waveform morphology and ICP levels, R²=0.66, P < 0.001. Conclusion: The brain pulse monitor’s PPG waveform demonstrated morphological features were similar to the invasive ICP waveform over a range of ICP levels, these features may provide a method to measure ICP levels. Trial Registration: ACTRN12620000828921.