Interpretation of vaccine associated neurological adverse events:a methodological and historical review

As a result of significant recent scientific investment, the range of vaccines available for COVID-19 prevention continues to expand and uptake is increasing globally. Although initial trial safety data have been generally reassuring, a number of adverse events, including vaccine induced thrombosis and thrombocytopenia (VITT), have come to light which have the potential to undermine the success of the vaccination program. However, it can be difficult to interpret available data and put these into context and to communicate this effectively. In this review, we discuss contemporary methodologies employed to investigate possible associations between vaccination and adverse neurological outcomes and why determining causality can be challenging. We demonstrate these issues by discussing relevant historical exemplars and explore the relevance for the current pandemic and vaccination program. We also discuss challenges in understanding and communicating such risks to clinicians and the general population within the context of the ‘infodemic’ facilitated by the Internet and other media

A time and motion study of patients presenting at the accident and emergency department at Mater Dei Hospital

<p>Abstract</p> <p>Background</p> <p>To carry out a time and motion study of patients presenting at the Emergency Department (ED) by measuring waiting times at the ED dept throughout the day. The objectives were:</p> <p indent="1">• to determine whether waiting times are prolonged, and</p> <p indent="1">• if prolonged, at which station(s) bottlenecks occur most often in terms of duration and frequency.</p> <p>Results will be compared to the United Kingdom guidelines of stay at the emergency department.</p> <p>Methods</p> <p>A group of 11 medical students monitored all patients who attended ED between 0600 hours on the 25^thAugust and 0600 hours on the 1st September 2008. For each 24 hour period, students were assigned to the triage room and the 3 priority areas where they monitored all patient-related activity, movement and waiting times so that length of stay (LOS) could be recorded. The key data recorded included patient characteristics, waiting times at various ED process stages, tests performed, specialist consultations and follow up until admitted, discharged, or referred to another hospital area. Average waiting times were calculated for each priority area. Bottle-necks and major limiting factors were identified. Results were compared against the United Kingdom benchmarks - i.e. 1 hour until first assessment, and 4 hours before admitting/discharge.</p> <p>Results</p> <p>1779 patients presented to the ED in the week monitored. As expected, patients in the lesser priority areas (i.e. 2 & 3) waited longer before being assessed by staff. Patients requiring laboratory and imaging investigations had a prolonged length of stay, which varied depending on specific tests ordered. Specialty consultation was associated with longer waiting times. A major bottleneck identified was waiting times for inpatient admission.</p> <p>Conclusions</p> <p>In conclusion, it was found that 30.3% of priority 1 patients, 86.3% of priority 2 patients and 76.8% of priority 3 patients waited more than 1 hour for first assessment. We conclude by proposing several changes that may expedite throughput.</p

Beam feasibility study of a collimator with in-jaw beam position monitors

At present, the beam-based alignment of the LHC collimators is performed by touching the beam halo with both jaws of each collimator. This method requires dedicated fills at low intensities that are done infrequently and makes this procedure time consuming. This limits the operational flexibility, in particular in the case of changes of optics and orbit configuration in the experimental regions. The performance of the LHC collimation system relies on the machine reproducibility and regular loss maps to validate the settings of the collimator jaws. To overcome these limitations and to allow a continuous monitoring of the beam position at the collimators, a design with jaw-integrated Beam Position Monitors (BPMs) was proposed and successfully tested with a prototype (mock-up) collimator in the CERN SPS. Extensive beam experiments allowed to determine the achievable accuracy of the jaw alignment for single and multi-turn operation. In this paper, the results of these experiments are discussed. The non-linear response of the BPMs is compared to the predictions from electromagnetic simulations. Finally, the measured alignment accuracy is compared to the one achieved with the present collimators in the LHC.peer-reviewe

Missense mutations in small muscle protein X-linked (SMPX) cause distal myopathy with protein inclusions

Using deep phenotyping and high-throughput sequencing, we have identified a novel type of distal myopathy caused by mutations in the Small muscle protein X-linked (SMPX) gene. Four different missense mutations were identified in ten patients from nine families in five different countries, suggesting that this disease could be prevalent in other populations as well. Haplotype analysis of patients with similar ancestry revealed two different founder mutations in Southern Europe and France, indicating that the prevalence in these populations may be higher. In our study all patients presented with highly similar clinical features: adult-onset, usually distal more than proximal limb muscle weakness, slowly progressing over decades with preserved walking. Lower limb muscle imaging showed a characteristic pattern of muscle involvement and fatty degeneration. Histopathological and electron microscopic analysis of patient muscle biopsies revealed myopathic findings with rimmed vacuoles and the presence of sarcoplasmic inclusions, some with amyloid-like characteristics. In silico predictions and subsequent cell culture studies showed that the missense mutations increase aggregation propensity of the SMPX protein. In cell culture studies, overexpressed SMPX localized to stress granules and slowed down their clearance.Peer reviewe

Missense mutations in small muscle protein X-linked (SMPX) cause distal myopathy with protein inclusions

Using deep phenotyping and high-throughput sequencing, we have identified a novel type of distal myopathy caused by mutations in the Small muscle protein X-linked (SMPX) gene. Four different missense mutations were identified in ten patients from nine families in five different countries, suggesting that this disease could be prevalent in other populations as well. Haplotype analysis of patients with similar ancestry revealed two different founder mutations in Southern Europe and France, indicating that the prevalence in these populations may be higher. In our study all patients presented with highly similar clinical features: adult-onset, usually distal more than proximal limb muscle weakness, slowly progressing over decades with preserved walking. Lower limb muscle imaging showed a characteristic pattern of muscle involvement and fatty degeneration. Histopathological and electron microscopic analysis of patient muscle biopsies revealed myopathic findings with rimmed vacuoles and the presence of sarcoplasmic inclusions, some with amyloid-like characteristics. In silico predictions and subsequent cell culture studies showed that the missense mutations increase aggregation propensity of the SMPX protein. In cell culture studies, overexpressed SMPX localized to stress granules and slowed down their clearance

The Effects of Structure Thickness, Air Gap Thickness and Silicon Type on the Performance of a Horizontal Electrothermal MEMS Microgripper

The ongoing development of microelectromechanical systems (MEMS) over the past decades has made possible the achievement of high-precision micromanipulation within the micromanufacturing, microassembly and biomedical fields. This paper presents different design variants of a horizontal electrothermally actuated MEMS microgripper that are developed as microsystems to micromanipulate and study the deformability properties of human red blood cells (RBCs). The presented microgripper design variants are all based on the U-shape `hot and cold arm’ actuator configuration, and are fabricated using the commercially available Multi-User MEMS Processes (MUMPs®) that are produced by MEMSCAP, Inc. (Durham, NC, USA) and that include both surface micromachined (PolyMUMPs™) and silicon-on-insulator (SOIMUMPs™) MEMS fabrication technologies. The studied microgripper design variants have the same in-plane geometry, with their main differences arising from the thickness of the fabricated structures, the consequent air gap separation between the structure and the substrate surface, as well as the intrinsic nature of the silicon material used. These factors are all inherent characteristics of the specific fabrication technologies used. PolyMUMPs™ utilises polycrystalline silicon structures that are composed of two free-standing, independently stackable structural layers, enabling the user to achieve structure thicknesses of 1.5 μm, 2 μm and 3.5 μm, respectively, whereas SOIMUMPs™ utilises a 25 μm thick single crystal silicon structure having only one free-standing structural layer. The microgripper design variants are presented and compared in this work to investigate the effect of their differences on the temperature distribution and the achieved end-effector displacement. These design variants were analytically studied, as well as numerically modelled using finite element analysis where coupled electrothermomechanical simulations were carried out in CoventorWare® (Version 10, Coventor, Inc., Cary, NC, USA). Experimental results for the microgrippers’ actuation under atmospheric pressure were obtained via optical microscopy studies for the PolyMUMPs™ structures, and they were found to be conforming with the predictions of the analytical and numerical models. The focus of this work is to identify which one of the studied design variants best optimises the microgripper’s electrothermomechanical performance in terms of a sufficient lateral tip displacement, minimum out-of-plane displacement at the arm tips and good heat transfer to limit the temperature at the cell gripping zone, as required for the deformability study of RBCs