The Normal Fetal Heart Rate Study: Analysis Plan

Recording of fetal heart rate via CTG monitoring has been routinely performed as an important part of antenatal and subpartum care for several decades. The current guidelines of the FIGO (ref1) recommend a normal range of the fetal heart rate from 110 to 150 bpm. However, there is no agreement in the medical community whether this is the correct range (ref2). We aim to address this question by computerized analysis (ref 3) of a high quality database (HQDb, ref 4) of about one billion electronically registered fetal heart rate measurements from about 10,000 pregnancies in three medical centres over seven years. In the present paper, we lay out a detailed analysis plan for this evidence-based project in the vein of the validation policy of the Sylvia Lawry Centre for Multiple Sclerosis Research (ref 5) with a split of the database into an exploratory part and a part reserved for validation. We will perform the analysis and the validation after publication of this plan in order to reduce the probability of publishing false positive research findings (ref 6-7)

Biological Breathalyzer

The aim of this research is the construction of a biological breathalyzer through synthetic biology, specifically through use of the metabolic pathways of a species of the Pichia taxa. The yeast utilized is able to metabolize both ethanol and methanol. However, when both ethanol and methanol are present, the yeast prefers to metabolize ethanol such that an AOX gene is not expressed because the first known by-product of methanol metabolism is the AO enzyme from the AOX gene. The AOX gene promoter is fused with a fluorescence protein gene so expression of the AOX gene can be visually detected. When the cell is supplied with both ethanol and methanol, the amount of time before fluorescence will correspond to the amount of ethanol given to the cell. In this way, the concentration of ethanol can be determined

Design and Testing of a Biological Breathalyzer

The aim of this research is the construction of a biological breathalyzer through synthetic biology. The metabolic pathways of a species of the Pichia taxa are used. The yeast is able to metabolize both ethanol and methanol. The first known by-product of methanol metabolism is the AO enzyme from the AOX gene. When both ethanol and methanol are present, the yeast prefers to metabolize ethanol, so the AOX gene is not expressed. The AOX gene promoter is fused with a fluorescence protein gene so expression of the AOX gene can be visually detected. When the cell is supplied with both ethanol and methanol, the amount of time before fluorescence will correspond to the amount of ethanol given to the cell. In this way, the concentration of ethanol can be determined

ISSM: Ice Sheet System Model

In order to have the capability to use satellite data from its own missions to inform future sea-level rise projections, JPL needed a full-fledged ice-sheet/iceshelf flow model, capable of modeling the mass balance of Antarctica and Greenland into the near future. ISSM was developed with such a goal in mind, as a massively parallelized, multi-purpose finite-element framework dedicated to ice-sheet modeling. ISSM features unstructured meshes (Tria in 2D, and Penta in 3D) along with corresponding finite elements for both types of meshes. Each finite element can carry out diagnostic, prognostic, transient, thermal 3D, surface, and bed slope simulations. Anisotropic meshing enables adaptation of meshes to a certain metric, and the 2D Shelfy-Stream, 3D Blatter/Pattyn, and 3D Full-Stokes formulations capture the bulk of the ice-flow physics. These elements can be coupled together, based on the Arlequin method, so that on a large scale model such as Antarctica, each type of finite element is used in the most efficient manner. For each finite element referenced above, ISSM implements an adjoint. This adjoint can be used to carry out model inversions of unknown model parameters, typically ice rheology and basal drag at the ice/bedrock interface, using a metric such as the observed InSAR surface velocity. This data assimilation capability is crucial to allow spinning up of ice flow models using available satellite data. ISSM relies on the PETSc library for its vectors, matrices, and solvers. This allows ISSM to run efficiently on any parallel platform, whether shared or distrib- ISSM: Ice Sheet System Model NASA's Jet Propulsion Laboratory, Pasadena, California uted. It can run on the largest clusters, and is fully scalable. This allows ISSM to tackle models the size of continents. ISSM is embedded into MATLAB and Python, both open scientific platforms. This improves its outreach within the science community. It is entirely written in C/C++, which gives it flexibility in its design, and the power/speed that C/C++ allows. ISSM is svn (subversion) hosted, on a JPL repository, to facilitate its development and maintenance. ISSM can also model propagation of rifts using contact mechanics and mesh splitting, and can interface to the Dakota software. To carry out sensitivity analysis, mesh partitioning algorithms are available, based on the Scotch, Chaco, and Metis partitioners that ensure equal area mesh partitions can be done, which are then usable for sampling and local reliability methods

Construction and Testing of a Biological Breathalyzer

The ultimate goal of this research was the construction of a biological breathalyzer using methods of synthetic biology. The metabolic pathways of Pichia taxa were utilized for this research. This yeast is able to metabolize both ethanol and methanol present in the environment. The first known by-product of methanol metabolism is the AO enzyme from the AOX gene. When both ethanol and methanol are present, the yeast preferentially metabolizes ethanol and the AOX gene is not expressed. By fusing the AOX gene promoter with a fluorescence protein gene, the expression of the AOX gene may be visually detected. When the organism is supplied with both ethanol and methanol, the amount of time before fluorescence will correspond to the amount of ethanol fed to the cell. In this way, the concentration of ethanol can be determined

Synthesis of a Biological Breathalyzer

The aim of this research is the construction of a biological breathalyzer through the culturing of yeast cells that can be used to measure concentrations of ethanol. The project makes use of the metabolic pathways of species of the Pichia taxa that are able to metabolize both ethanol and methanol. The yeast prefers to metabolize ethanol when both methanol and ethanol are present and will therefore consume ethanol before methanol. The AO enzyme, from the AOX gene, appears to be the first enzyme produced by the metabolism of methanol. The AOX gene will not be expressed in the cell when ethanol is present since ethanol is being metabolized rather than methanol. Fusing the AOX gene promoter with the DNA sequence to a fluorescent protein will allow the expression of the AOX gene, and therefore the metabolism of methanol, to be visually detected. In supplying the yeast cells with ethanol and methanol simultaneously, the cells will produce the fluorescent protein once the ethanol is utilized. This will result in a visible fluorescent light. The concentration of ethanol can be determined by measuring the time before the fluorescent light is emitted. Determining the concentration of ethanol present will make plausible the construction of a breathalyzer device to detect the blood alcohol level in an individual and could lead to the development of additional sensor systems to detect the presence and concentration of solvents. The AOX gene promoter was cloned and the linking of the promoter to the red fluorescent protein gene is in progress

ESTABLISHING A PLATFORM FOR SPRAY DRYING INHALABLE VACCINES IN SOUTH AFRICA

Mycobacterium bovis BCG is the current vaccine for tuberculosis (TB). However, BCG as it is currently administered shows highly variable efficacy in protecting adults against TB. The natural route of infection of TB is via inhalation of bacilli-containing aerosols and it is postulated that immunization by the natural route of infection may lead to a greater immunity given the fact that the lungs are the primary target of infection. By eliciting both local and systemic immune responses, it is anticipated that an inhaled form of BCG will offer greater protection against pulmonary TB. Current commercial BCG vaccine preparations are filled as bacterial suspensions in vials, dried through lyophilization and stabilized through refrigeration with a one year shelf life. However, freeze-dried BCG does not exhibit a particle form conducive for delivery via the aerosol route and must be injected. Spray drying studies by Harvard University and Medicine in Need (MEND) scientists have demonstrated that BCG could be spray dried into a viable aerosol with up to 1 year of stability under refrigerated conditions, with the potential for room temperature stability. To support the further preclinical development of the BCG aerosol for application in the developing world, MEND established a state-of-the-art Biosafety level 3 spray drying facility with local expertise in South Africa, where the vaccine will be produced for an IND-enabling toxicology study meeting OECD Good Laboratory Practice (GLP) requirements. Frozen BCG bulk is spray dried and the resulting dry powder is characterized in terms of viability and aerosol properties. The dried BCG aerosol is then aseptically filled into capsules using a semi-automatic filling device for delivery using a low-cost hand-held inhaler. In conclusion, the spray drying technology was successfully transferred from Harvard University to the MEND facility in Pretoria. MEND is developing local expertise and infrastructure to support further preclinical and clinical development of BCG for inhalation

Transcervical intrauterine radiofrequency ablation of fibroids in high-risk patients with bleeding disorder

Objectives: To show the advantages of transcervical radiofrequency ablation (TRFA) in high-risk patients with bleeding disorder. Material and methods: It is a retrospective analysis. The study included only patients with known pre-existing conditions (obesity, cardiac and neurological disease, coagulation disorder, anaemia) or post-surgical conditions who were treated with the Sonata® System for fibroid-related bleeding complaints at Academic Hospital Cologne Weyertal between January 2015 and March 2021. These patients were classified as high-risk patients. The fibroids were mostly determined due transvaginal sonography. Thirty patients were included, and 43 fibroids were determined. Results: Therapy with the Sonata® system could be performed without complications in all cases. In our analysis, improvement of fibroid-related symptoms was observed in 89% of cases. Conclusions: The Sonata® System is on the one hand minimally invasive, uncomplicated and fast and on the other hand a successful method of fibroid therapy, which is particularly suitable for high-risk patients with various pre-existing conditions, for whom a minimally invasive, bloodless and short surgical procedure has great advantages