LipoDDx: a mobile application for identification of rare lipodystrophy syndromes

BACKGROUND: Lipodystrophy syndromes are a group of disorders characterized by a loss of adipose tissue once other situations of nutritional deprivation or exacerbated catabolism have been ruled out. With the exception of the HIV-associated lipodystrophy, they have a very low prevalence, which together with their large phenotypic heterogeneity makes their identification difficult, even for endocrinologists and pediatricians. This leads to significant delays in diagnosis or even to misdiagnosis. Our group has developed an algorithm that identifies the more than 40 rare lipodystrophy subtypes described to date. This algorithm has been implemented in a free mobile application, LipoDDx(R). Our aim was to establish the effectiveness of LipoDDx(R). Forty clinical records of patients with a diagnosis of certainty of most lipodystrophy subtypes were analyzed, including subjects without lipodystrophy. The medical records, blinded for diagnosis, were evaluated by 13 physicians, 1 biochemist and 1 dentist. Each evaluator first gave his/her results based on his/her own criteria. Then, a second diagnosis was given using LipoDDx(R). The results were analysed based on a score table according to the complexity of each case and the prevalence of the disease. RESULTS: LipoDDx(R) provides a user-friendly environment, based on usually dichotomous questions or choice of clinical signs from drop-down menus. The final result provided by this app for a particular case can be a low/high probability of suffering a particular lipodystrophy subtype. Without using LipoDDx(R) the success rate was 17 +/- 20%, while with LipoDDx(R) the success rate was 79 +/- 20% (p < 0.01). CONCLUSIONS: LipoDDx(R) is a free app that enables the identification of subtypes of rare lipodystrophies, which in this small cohort has around 80% effectiveness, which will be of help to doctors who are not experts in this field. However, it will be necessary to analyze more cases in order to obtain a more accurate efficiency value

Correction for Lebrato et al., Global variability in seawater Mg:Ca and Sr:Ca ratios in the modern ocean

4 pages, 5 figures.-- Correction Global variability in seawater Mg:Ca and Sr:Ca ratios in the modern ocean; Proceedings of the National Academy of Sciences of the USA 117(36): 22281-22292 (2020); doi: 10.1073/pnas.1918943117; http://hdl.handle.net/10261/221953The authors wish to note the following: “This study’s seawater Sr:Ca values were systematically low as a consequence of normalization to another published low value for the International Association for the Physical Sciences of the Oceans (IAPSO) (1). IAPSO has been used at the Ocean Drilling Program, Texas A&M University (ODP-TAMU) (http://www-odp.tamu.edu/), and is still being used as the primary standard for elemental composition of seawater/interstitial water. Consequently, our seawater value of Sr:Ca = 8.28 mmol:mol was systematically low by approx. 3.70%, if we accept seawater Sr:Ca 8.60 mmol:mol as the recommended value for IAPSO North Atlantic surface water salinity standard. The uncertainty budget should be expanded including the uncertainty of IAPSO composition. The largest contribution to expanded uncertainty of our data comes from the uncertainty of the IAPSO reference composition, which is 3.29% using all published values. This will result in 3.30% (1 SD) expanded uncertainty for seawater Sr:Ca (and 0.5%, for seawater Mg:Ca) of the entire data set with respect to accuracy. We have corrected all seawater Sr:Ca values with a factor of 1.0243 in all our tables (e.g., SI Appendix, Table S1 averages) and in the figures (Fig. 4, Fig. 5), where a ratio was used. Note that the seawater Sr:Ca % changes are small, thus changes are hardly noticeable on large displays (e.g., Figures), but they can be seen in the tables and averages/SD calculations. Seawater Sr:Ca ratios are also corrected in the main text where relevantPeer reviewe

An Area-Aggregated Dynamic Traffic Simulation Model

Microscopic and macroscopic dynamic traffic models not fast enough to run in an optimization loop to coordinate traffic measures over areas of twice a trip length (50x50 km). Moreover, in strategic planning there are models with a spatial high level of detail, but lacking the features of traffic dynamics. This paper introduces the Network Transmission Model (NTM), a model based on areas, exploiting the Macroscopic or Network Fundamental Diagram (NFD). For the first time, a full operational model is proposed which can be implemented in a network divided into multiple subnetworks, and the physical properties of spillback of traffic jams for subnetwork to subnetwork is ensured. The proposed model calculates the traffic flow between to cell as the minimum of the demand in the origin cell and the supply in the destination cell. The demand first increasing and then decreasing as function of the accumulation in the cell; the supply is first constant and then decreasing as function of the accumulation. Moreover, demand over the boundaries of two cells is restricted by a capacity. This system ensures that traffic characteristics move forward in free flow, congestion moves backward and the NFD is conserved. Adding the capacity gives qualitatively reasonable effects of inhomogeneity. The model applied on a test case with multiple destinations, and re-routing and perimeter control are tested as control measures.Transport & PlanningCivil Engineering and Geoscience

Removal of organic magnesium in coccolithophore calcite

Coccolithophore calcite refers to the plates of calcium carbonate (CaCO3) produced by the calcifying phytoplankton, coccolithophores. The empirical study of the elemental composition has a great potential in the development of paleoproxies. However, the difficulties to separate coccolithophore carbonates from organic phases hamper the investigation of coccoliths magnesium to calcium ratios (Mg/Ca) in biogeochemical studies. Magnesium (Mg) is found in organic molecules in the cells at concentrations up to 400 times higher than in inorganically precipitated calcite in present-day seawater. The aim of this study was to optimize a reliable procedure for organic Mg removal from coccolithophore samples to ensure reproducibility in measurements of inorganic Mg in calcite. Two baseline methods comprising organic matter oxidations with (1) bleach and (2) hydrogen peroxide (H2O2) were tested on synthetic pellets, prepared by mixing reagent grade CaCO3 with organic matter from the non-calcifying marine algae Chlorella autotrophica and measured with an ICP-AES (inductively coupled plasma-atomic emission spectrometer). Our results show that treatments with a reductive solution [using hydroxylamine-hydrochloride (NH2OH·HCl + NH4OH)] followed by three consecutive oxidations (using H2O2) yielded the best cleaning efficiencies, removing &gt;99% of organic Mg in 24 h. P/Ca and Fe/Ca were used as indicators for organic contamination in the treated material. The optimized protocol was tested in dried coccolithophore pellets from batch cultures of Emiliania huxleyi, Calcidiscus leptoporus and Gephyrocapsa oceanica. Mg/Ca of treated coccolithophores were 0.151 ± 0.018, 0.220 ± 0.040, and 0.064 ± 0.023 mmol/mol, respectively. Comparison with Mg/Ca literature coccolith values, suggests a tight dependence on modern seawater Mg/Ca, which changes as a consequence of different seawater origins (&lt;10%). The reliable determination of Mg/Ca and Sr/Ca, and the low levels of organic contamination (Fe/Ca and P/Ca) make this protocol applicable to field and laboratory studies of trace elemental composition in coccolithophore calcite

Southern Ocean phytoplankton physiology in a changing climate

The Southern Ocean (SO) is a major sink for anthropogenic atmospheric carbon dioxide(CO2), potentially harbouring even greater potential for additional sequestration of CO2 through enhanced phytoplankton productivity. In the SO, primary productivity is primarily driven by bottom up processes (physical and chemical conditions) which are spatially and temporally heterogeneous. Due to a paucity of trace metals (such as iron) and high variability in light, much of the SO is characterised by an ecological paradox of high macronutrient concentrations yet uncharacteristically low chlorophyll concentrations. It is expected that with increased anthropogenic CO2 emissions and the coincident warming, the major physical and chemical process that govern the SO will alter, influencing the biological capacity and functioning of the ecosystem. This review focuses on the SO primary producers and the bottom up processes that underpin their health and productivity. It looks at the major physicochemical drivers of change in the SO, and based on current physiological knowledge, explores how these changes will likely manifest in phytoplankton, specifically, what are the physiological changes and floristic shifts that are likely to ensue and how this may translate into changes in the carbon sink capacity, net primary productivity and functionality of the SO

Global variability in seawater Mg:Ca and Sr:Ca ratios in the modern ocean

Seawater Mg:Ca and Sr:Ca ratios are biogeochemical parameters reflecting the Earth-ocean-atmosphere dynamic exchange of elements. The ratios' dependence on the environment and organisms' biology facilitates their application in marine sciences. Here, we present a measured single-laboratory dataset, combined with previous data, to test the assumption of limited seawater Mg:Ca and Sr:Ca variability across marine environments globally. High variability was found in open-ocean upwelling and polar regions, shelves/neritic and river-influenced areas, where seawater Mg:Ca and Sr:Ca ratios range from similar to 4.40 to 6.40 mmol:mol and similar to 6.95 to 9.80 mmol:mol, respectively. Open-ocean seawater Mg:Ca is semi-conservative (similar to 4.90 to 5.30 mol:mol), while Sr:Ca is more variable and nonconservative (similar to 7.70 to 8.80 mmol:mol); both ratios are nonconservative in coastal seas. Further, the Ca, Mg, and Sr elemental fluxes are connected to large total alkalinity deviations from International Association for the Physical Sciences of the Oceans (IAPSO) standard values. Because there is significant modern seawater Mg:Ca and Sr:Ca ratios variability across marine environments we cannot absolutely assume that fossil archives using taxa-specific proxies reflect true global seawater chemistry but rather taxa- and process-specific ecosystem variations, reflecting regional conditions. This variability could reconcile secular seawater Mg:Ca and Sr:Ca ratio reconstructions using different taxa and techniques by assuming an error of 1 to 1.50 mol:mol, and 1 to 1.90 mmol:mol, respectively. The modern ratios' variability is similar to the reconstructed rise over 20 Ma (Neogene Period), nurturing the question of semi-nonconservative behavior of Ca, Mg, and Sr over modern Earth geological history with an overlooked environmental effect