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)

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

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

Future Climate and Land Use Change Impacts on River Flows in the Tapajós Basin in the Brazilian Amazon

Abstract Land conversion and changing climate are expected to significantly alter tropical forest hydrology. We used a land surface model integrated with a river routing scheme to analyze the hydrological alterations expected in the Tapajós River basin, a large portion of the Brazilian Amazon, caused by two environmental drivers: climate and land use. The model was forced with two future climate scenarios (years 2026–2045) from the Earth System Model HadGem2‐ES with moderate (+4.5 W/m2 radiative forcing value in the year 2100 with respect to preindustrial levels) and severe (+8.5 W/m2) representative atmospheric carbon dioxide pathways (Representative Concentration Pathways). We tested the sensitivity of our results to the uncertainty in future climate projections by running simulations with IPSL‐CM5 (wettest scenarios) and GISS‐E2 (driest scenarios). Human land use effects on vegetation were evaluated using a limited and an extreme deforestation scenario. Our analysis indicates that climate change is predicted to reduce river flows across seasons (up to 20%) and bring a considerable shift in flow seasonality toward a later onset (nearly 1.5 months) and increase in interannual variability. While land use change partially counteracts the climate‐driven diminishing trend in river flows, it is expected to contribute to a further increase in interannual and intraannual variability. From a water management perspective, the overall reduction of river flows and their increased variability, combined with the shift and the shortening of the wet season, could potentially affect the productivity of the large hydropower systems planned for the region and the growing demand for agricultural and transport expansion

The key physical parameters governing frictional dissipation in a precipitating atmosphere

Precipitation generates small-scale turbulent air flows the energy of which ultimately dissipates to heat. The power of this process has previously been estimated to be around 2-4 W m-2 in the tropics: a value comparable in magnitude to the dynamic power of the global circulation. Here we suggest that this previous power estimate is approximately double the true figure. Our result reflects a revised evaluation of the mean precipitation path length Hp. We investigate the dependence of Hp on surface temperature,relative humidity,temperature lapse rate and degree of condensation in the ascending air. We find that the degree of condensation,defined as the relative change of the saturated water vapor mixing ratio in the region of condensation, is a major factor determining Hp. We estimate from theory that the mean large-scale rate of frictional dissipation associated with total precipitation in the tropics lies between 1 and 2 W m-2 and show that our estimate is supported by empirical evidence. We show that under terrestrial conditions frictional dissipation constitutes a minor fraction of the dynamic power of condensation-induced atmospheric circulation,which is estimated to be at least 2.5 times larger. However,because Hp increases with surface temperature Ts, the rate of frictional dissipation would exceed that of condensation-induced dynamics, and thus block major circulation, at Ts >~320 K in a moist adiabatic atmosphere.Comment: 12 pp, 2 figure