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    Edward J Botcherby

    Experience in the management of COVID-19 vaccine induced thrombosis and thrombocytopenia is currently lacking. In this case series we report the presentation and our experience in the management of cerebral venous sinus thrombosis and... more
    Experience in the management of COVID-19 vaccine induced thrombosis and thrombocytopenia is currently lacking. In this case series we report the presentation and our experience in the management of cerebral venous sinus thrombosis and thrombocytopenia post ChAdOx1 nCoV-19 vaccination. Two of the three cases had confirmed anti-platelet factor 4 antibodies and extracranial thrombosis. In all the cases, plasma exchange, intravenous immunoglobulins and steroids normalised the platelet count and intravenous argatroban was used for initial anticoagulation. Two cases received a platelet transfusion and required decompressive hemicraniectomy due to raised intracranial pressure, secondary to cerebral oedema and haemorrhage. Prompt assessment of a new persistent headache occurring between 5 and 28 days of receiving the ChAdOx1 nCoV-19 vaccine is warranted irrespective of age. In cases with venous thrombosis on imaging or abnormal laboratory findings (thrombocytopenia, abnormal clotting or ele...
    Background Despite significant improvement in the management of patients with implantable cardioverter-defibrillators (ICDs), many patients still receive ICD shocks in the community and present to emergency departments. These urgent... more
    Background Despite significant improvement in the management of patients with implantable cardioverter-defibrillators (ICDs), many patients still receive ICD shocks in the community and present to emergency departments. These urgent admissions are poorly described in the wider literature. Purpose To describe the characteristics of emergency presentations for ICD shocks. Methods From November 2011 to November 2014, all patients admitted to the cardiac emergency department of Lille University Hospital for ICD shock(s) were prospectively enrolled. Patient characteristics, investigation results, and details of electrical activities from ICD interrogation were recorded at presentation. Results In total, 109 emergency presentations for ICD shocks were recorded in 90 patients (85% male; 57 ± 16 years; ischemic cardiomyopathy: 49%; LVEF 34 ± 13%; secondary prevention: 68%). Overall, 83 (76%) were provoked by an appropriate index shock (AS), and 26 (24%) by an inappropriate index shock (IS). The majority of patients received multiples shocks (AS: 60%, IS: 81%). Of the 83 presentations for AS, 66 (80%) were triggered by monomorphic VTs and 43 (52%) were caused by electrical storms. The main reasons for IS were atrial fibrillation or flutter (62%) and sinus node tachycardia (19%). Overall, hospitalization was required in 82 cases (75%), with a median length of stay of 7 days [4–11]. Following presentation, the following measures were taken: change in ICD programming (45%), loading dose of amiodarone (33%), increase of β-blockers dosage (32%), VT ablation (18%), reintervention on the ICD system (6%). Conclusion Emergency presentations for ICD shocks remain frequent, and are caused by appropriate ICD therapies in 3 out of 4 cases. These admissions place a considerable burden on emergency and cardiology departments. Evidence-based strategies capable of reducing the incidence of emergency presentations for ICD shocks in the community should be more widely implemented.
    L'invention concerne un appareil de mise au point destine a etre utilise avec un systeme optique ayant une lentille objectif a ouverture numerique (ON) elevee (20), lequel appareil comprend des moyens (26) de formation et de capture... more
    L'invention concerne un appareil de mise au point destine a etre utilise avec un systeme optique ayant une lentille objectif a ouverture numerique (ON) elevee (20), lequel appareil comprend des moyens (26) de formation et de capture d'image pour former une image dans une zone d'image intermediaire (44) et pour capturer une image par la reception et la refocalisation de la lumiere a partir d'un plan focal selectionne dans ladite zone d'image intermediaire, et des moyens d'ajustement de foyer (28) pour ajuster la position du plan focal selectionne dans la zone d'image intermediaire. Les moyens (26) de formation et de capture d'image comprennent au moins une lentille a ON elevee. En utilisation, une aberration spherique introduite par la lentille objectif a ON elevee (20) est reduite.
    For the next generation of Linear Colliders (LC) the precision alignment of accelerator com- ponents will be critical. The DESY applied geodesy group has developed the concept of an automated "survey train". The train runs along... more
    For the next generation of Linear Colliders (LC) the precision alignment of accelerator com- ponents will be critical. The DESY applied geodesy group has developed the concept of an automated "survey train". The train runs along the accelerator wall measuring the 3D position of a set of equispaced reference markers. This reference structure is then used to align the accelerator
    Despite increased use of remote monitoring (RM) to follow up implantable cardioverter-defibrillator (ICD) recipients, many patients still receive ICD shocks in the community and present to the emergency department. Our aim was to identify... more
    Despite increased use of remote monitoring (RM) to follow up implantable cardioverter-defibrillator (ICD) recipients, many patients still receive ICD shocks in the community and present to the emergency department. Our aim was to identify the best predictors of impending shock delivery that can be measured with an ICD and to identify the most appropriate activities to alert physicians to during RM follow-up. All patients presenting to our institution for ICD shock, from November 2011 to November 2014, were enrolled in this prospective study. Patient characteristics, investigation results, and details of electrical activities from ICD interrogation were recorded at presentation. Presentations were classified as potentially avoidable if activities from a list of set criteria were apparent more than 48 h before index shock. Univariate and multivariate analyses were then used to identify predictors of potentially avoidable shocks. In total, 109 emergency presentations were recorded in 90 patients (male: 85%; 57 ± 16 years; ischaemic cardiomyopathy: 49%; LVEF: 34 ± 13%; electrical storm: 40%), of which 26 (24%) were potentially avoidable. Antitachycardia pacing (ATP) episodes were the most important predictor of impending shock. Potentially avoidable shocks were preceded by more episodes of ATP than unavoidable shocks (13 [3-67] vs. 3 [0-10]; P < 0.001). Patients followed up with RM systems configured to generate alerts following ATP delivery experienced significantly less ICD shocks (24 vs. 16%, P < 0.01). Remote monitoring systems that generate alerts following ATP delivery could reduce emergency presentations for ICD shock by 24%, as ATP is a key predictor of impending shock delivery.
    This study aims to study the clinical implications of the concomitant use of a left ventricular assist device (LVAD) and an implantable cardioverter-defibrillator (ICD). In this retrospective study, all patients who underwent LVAD (Heart... more
    This study aims to study the clinical implications of the concomitant use of a left ventricular assist device (LVAD) and an implantable cardioverter-defibrillator (ICD). In this retrospective study, all patients who underwent LVAD (Heart Mate II) implantation with concomitant ICD therapy at our institution between June 2007 and August 2012 were included. We sought to investigate (1) the electromagnetic interference between LVAD and ICD telemetry, (2) the effect of LVAD implantation on right ventricular (RV) lead parameters and (3) the ventricular tachyarrhythmias (VAs) that occur post-LVAD implantation. Of the 23 patients (53 ± 9 years, 73 % male, LVEF 19 ± 9 %) included, ICD telemetry was lost in four patients post-LVAD implantation (Saint-Jude-Medical Atlas V-193, V-240, V-243, and Sorin CRT-8750), prompting either use of a metal shield (n = 1), a change in position of the programmer head (n = 1) or ICD replacement (n = 2). LVAD implantation was associated with a decrease in both RV signal amplitude (p = 0.04) and RV impedance (p < 0.01), and a trend towards an increased RV pacing threshold (p = 0.08), without affecting clinical outcome. Eleven patients (47.8 %) experienced VAs after LVAD implantation, which on the whole were well tolerated. Their occurrence was strongly linked to a history of VAs before device implantation (p < 0.01). Electromagnetic interference between LVADs and ICD telemetry may necessitate ICD replacement. LVAD placement is associated with significant changes in RV lead parameters that have minimal clinical significance. VAs occur in approximately half of LVAD patients seen and their occurrence is strongly related to a history of VAs prior to LVAD implantation.
    In this paper, we present details of a scanning two-photon fluorescence microscope we have built with a nearisotropic scan rate. This means that the focal spot can be scanned at high speed along any direction in the specimen, without... more
    In this paper, we present details of a scanning two-photon fluorescence microscope we have built with a nearisotropic scan rate. This means that the focal spot can be scanned at high speed along any direction in the specimen, without introducing systematic aberrations. We present experimental point spread function measurements for this system using an Olympus 1.4 NA 60X oil immersion lens that demonstrates an axial range of operation greater than 70 μm. We give details of a novel actuator device used to displace the focusing element and demonstrate axial scan responses up to 3.5 kHz. Finally, we present an application of this system in liquid crystal research to image the dynamic response of a nematic device during switching. Information about the director field at different levels in the device can be inferred from images acquired with a temporal resolution of 2.5 ms.
    ABSTRACT In this paper, we present details of a scanning two-photon fluorescence microscope we have built with a nearisotropic scan rate. This means that the focal spot can be scanned at high speed along any direction in the specimen,... more
    ABSTRACT In this paper, we present details of a scanning two-photon fluorescence microscope we have built with a nearisotropic scan rate. This means that the focal spot can be scanned at high speed along any direction in the specimen, without introducing systematic aberrations. We present experimental point spread function measurements for this system using an Olympus 0.8 NA 40X water dipping objective lens that demonstrates an axial range of operation greater than 200 mum. We give details of a novel actuator device used to displace the focusing element and demonstrate axial scan responses up to 3.5 kHz. Finally, we present a bioscience application of this system to image dendritic processes that follow non-linear paths in three-dimensional space. The focal spot was scanned along one such process at 400 Hz with an axial range of more than 90 mum.
    ABSTRACT We describe a method of optical refocusing for high numerical aperture systems that is particularly relevant for confocal and multiphoton microscopy. Crucially the method avoids spherical aberration that is common to other... more
    ABSTRACT We describe a method of optical refocusing for high numerical aperture systems that is particularly relevant for confocal and multiphoton microscopy. Crucially the method avoids spherical aberration that is common to other optical refocussing systems. Further refocusing is implemented remotely from the specimen.
    As a main pigment in skin tissues, melanin plays an important role in photo-protecting skin from UV radiation. However, melanogenesis may be altered due to disease or environmental factors; for example, sun exposure may cause damage and... more
    As a main pigment in skin tissues, melanin plays an important role in photo-protecting skin from UV radiation. However, melanogenesis may be altered due to disease or environmental factors; for example, sun exposure may cause damage and mutation of melanocytes and induce melanoma. Imaging pigmentation changes may provide invaluable information to catch the malignant transformation in its early stage and
    ABSTRACT We demonstrate a simple and light-efficient way of generating non-diffracting Bessel beams for use in confocal microscopy. A number of imaging modalities using such beams is discussed. Preliminary experimental results including... more
    ABSTRACT We demonstrate a simple and light-efficient way of generating non-diffracting Bessel beams for use in confocal microscopy. A number of imaging modalities using such beams is discussed. Preliminary experimental results including brightfield, fluorescence and two-photon images are presented.
    In this paper we describe a simple method of optical refocusing for high numerical aperture imaging systems. As the first stage of this new method satisfies both the sine and Herschel conditions of geometric optics, images obtained are... more
    In this paper we describe a simple method of optical refocusing for high numerical aperture imaging systems. As the first stage of this new method satisfies both the sine and Herschel conditions of geometric optics, images obtained are free from spherical aberration over a large scan range.
    In this paper, we present a novel technique that permits sectioning microscopes to refocus and acquire images from a large range of specimen depths without introducing movements near the specimen. In contrast to other such remote focusing... more
    In this paper, we present a novel technique that permits sectioning microscopes to refocus and acquire images from a large range of specimen depths without introducing movements near the specimen. In contrast to other such remote focusing methods, this technique avoids systematic aberrations that degrade image quality when imaging planes away from the optimal focal plane. Furthermore, the specific geometry
    ABSTRACT In this paper, we present details of a scanning two-photon fluorescence microscope we have built with a nearisotropic scan rate. This means that the focal spot can be scanned at high speed along any direction in the specimen,... more
    ABSTRACT In this paper, we present details of a scanning two-photon fluorescence microscope we have built with a nearisotropic scan rate. This means that the focal spot can be scanned at high speed along any direction in the specimen, without introducing systematic aberrations. We present experimental point spread function measurements for this system using an Olympus 1.4 NA 60X oil immersion lens that demonstrates an axial range of operation greater than 70 mum. We give details of a novel actuator device used to displace the focusing element and demonstrate axial scan responses up to 3.5 kHz. Finally, we present an application of this system in liquid crystal research to image the dynamic response of a nematic device during switching. Information about the director field at different levels in the device can be inferred from images acquired with a temporal resolution of 2.5 ms.
    The standard microscope architecture around which confocal microscopes are built imposes fundamental restrictions on the speed with which images (three-dimensional data sets) can be obtained. Commercially available slit scanning confocal... more
    The standard microscope architecture around which confocal microscopes are built imposes fundamental restrictions on the speed with which images (three-dimensional data sets) can be obtained. Commercially available slit scanning confocal microscopes are able to produce optically sectioned images at frame rates well in excess of 100 Hz. However only the focal (x-y) plane can be imaged at this speed. To image a volume specimen it is necessary to physically change the distance between the objective lens and the specimen. This refocusing process is often necessarily slow and represents a bottleneck to the speed of image acquisition. We describe the construction of a slit scanning confocal microscope based on what we know to be a novel microscope architecture, which permits images of other planes and, particular, the meridional (x-z) plane to be acquired in real time.
    We describe an optical microscope system whose focal setting can be changed quickly without moving the objective lens or specimen. Using this system, diffraction limited images can be acquired from a wide range of focal settings without... more
    We describe an optical microscope system whose focal setting can be changed quickly without moving the objective lens or specimen. Using this system, diffraction limited images can be acquired from a wide range of focal settings without introducing optical aberrations that degrade image quality. We combine this system with a real time Nipkow disc based confocal microscope so as to permit the acquisition of extended depth of field images directly in a single frame of the CCD camera. We also demonstrate a simple modification that enables extended depth of field images to be acquired from different angles of perspective, where the angle can be changed over a continuous range by the user in real-time.
    ... In the low numerical aperture case the field in the focal region of the objective lens is given by the Fourier transform of the pupil function P(R) however the situation is slightly more complicated for high NA objectives because... more
    ... In the low numerical aperture case the field in the focal region of the objective lens is given by the Fourier transform of the pupil function P(R) however the situation is slightly more complicated for high NA objectives because substantial portions of the wavefront are refracted ...
    Sarcomere length (SL) is a key indicator of cardiac mechanical function, but current imaging technologies are limited in their ability to unambiguously measure and characterize SL at the cell level in intact, living tissue. We developed a... more
    Sarcomere length (SL) is a key indicator of cardiac mechanical function, but current imaging technologies are limited in their ability to unambiguously measure and characterize SL at the cell level in intact, living tissue. We developed a method for measuring SL and regional cell orientation using remote focusing microscopy, an emerging imaging modality that can capture light from arbitrary oblique planes within a sample. We present a protocol that unambiguously and quickly determines cell orientation from user-selected areas in a field of view by imaging 2 oblique planes that share a common major axis with the cell. We demonstrate the effectiveness of the technique in establishing single-cell SL in Langendorff-perfused hearts loaded with the membrane dye di-4-ANEPPS. Remote focusing microscopy can measure cell orientation in complex 2-photon data sets without capturing full z stacks. The technique allows rapid assessment of SL in healthy and diseased heart experimental preparations.
    We demonstrate an improved image-forming optics for transmission optical projection tomography (TOPT), with which the parallel integral throughout an object can be obtained. This is performed by introducing a shutter with an appropriate... more
    We demonstrate an improved image-forming optics for transmission optical projection tomography (TOPT), with which the parallel integral throughout an object can be obtained. This is performed by introducing a shutter with an appropriate diameter at the back focus of the objective lens. We evaluate and compare the performances of the improved and the conventional TOPT systems with different parameters to obtain the optimal configuration. The optimal reconstruction is achieved by the improved configuration with a= 0.8~ 1.6, ...
    Remote monitoring (RM) is increasingly used to follow up patients with implantable cardioverter-defibrillators (ICDs). Randomized control trials provide evidence for the benefit of this intervention, but data for RM in daily clinical... more
    Remote monitoring (RM) is increasingly used to follow up patients with implantable cardioverter-defibrillators (ICDs). Randomized control trials provide evidence for the benefit of this intervention, but data for RM in daily clinical practice with multiple-brands and unselected patients is lacking. To assess the effect of RM on patient management and clinical outcome for recipients of ICDs in daily practice. We reviewed ICD recipients followed up at our institution in 2009 with RM or with traditional hospital only (HO) follow-up. We looked at the effect of RM on the number of scheduled ambulatory follow-ups and urgent unscheduled consultations, the time between onset of asymptomatic events to clinical intervention and the clinical effectiveness of all consultations. We also evaluated the proportion of RM notifications representing clinically relevant situations. We included 355 patients retrospectively (RM: n=144, HO: n=211, 76.9% male, 60.3±15.2 years old, 50.1% with ICDs for primary prevention and mean left ventricular ejection fraction 35.5±14.5%). Average follow-up was 13.5 months. The RM group required less scheduled ambulatory follow-up consultations (1.8 vs. 2.1/patient/year; P<0.0001) and a far lower median time between the onset of asymptomatic events and clinical intervention (7 vs. 76 days; P=0.016). Of the 784 scheduled ambulatory follow-up consultations carried out, only 152 (19.4%) resulted in therapeutic intervention or ICD reprogramming. We also found that the vast majority of RM notifications (61.9%) were of no clinical relevance. RM allows early management of asymptomatic events and a reduction in scheduled ambulatory follow-up consultations in daily clinical practice, without compromising safety, endorsing RM as the new standard of care for ICD recipients.