Non-GH Agents and Novel Therapeutics in the Management of Short Stature

Short stature is one of the most common reasons for referral to pediatric endocrinologists. The vast majority of short children do not have growth hormone (GH) deficiency or another pathologic process that is interfering with normal growth. While GH has been approved in the US for several etiologies of non-GH deficient short stature, its high cost and need for daily injections represent barriers for many families. Alternative agents for the management of short stature include the use of gonadotropin releasing hormone analogs (GnRHas) to delay puberty, and aromatase inhibitors (AIs) in boys to postpone epiphyseal fusion. The results of studies employing GnRHas as either monotherapy or combined with GH are mixed, and there is a dearth of rigorously designed clinical trials that have followed patients to adult height. While AIs have been found to result in modest increases in adult height in some studies, important questions about their long-term safety exist. The C-type natriuretic peptide analog vosoritide is an experimental agent that is emerging as a potential treatment for a few specific conditions including achondroplasia, although its efficacy in attenuating disproportionality is as yet unproven. While each of these therapeutic strategies holds promise, none are currently considered standard of care and several important questions remain. These include the impact of these interventions on quality of life as well as long-term outcomes

Evaluation of Orbit Errors and Measurement Corrections in Differential Navigation With LEO Satellites

Ephemeris errors and measurement corrections in differential navigation with low Earth orbit (LEO) space vehicles (SVs) are analyzed. First, orbit errors are characterized for the non-differential case, showing the dependency of the range measurement errors on the receiver-to-SV geometry. The study is then extended to the differential case, where the maximum differential range error is found to occur when the baseline is normal to the projected measurement vector from one receiver onto the local navigation frame. A simulation study is presented to assess the differential navigation performance with 14 Starlink and 11 OneWeb LEO satellites. The framework fused differenced pseudorange measurements from a base and rover to LEO SVs with inertial measurement unit (IMU) measurements via an extended Kalman filter (EKF) in a tightly-coupled fashion to estimate the rover’s states. The simulation considered an aerial vehicle equipped with a tactical-grade IMU, an altimeter, a GNSS receiver, and a LEO receiver making pseudorange measurements to the LEO SVs. During 300 seconds of flight time, the vehicle traveled a distance of 28 km, the last 23 km of which were without GNSS, achieving a three-dimensional (3-D) position root mean squared error (RMSE) of 52 cm, compared to 12.5 m using the non-differential framework. Experimental results are presented, showing the potential of differential navigation in reducing ephemeris, clocks, and atmospheric errors. A ground vehicle traversed a distance of 540 m in 60 seconds, the last 492 m of which without GNSS signals, while making Doppler measurements to 2 Orbcomm and 1 Iridium LEO SVs, whose ephemerides were obtained from two-line element (TLE) files, propagated with simplified general perturbation 4 (SGP4) orbit propagator. The differential framework yielded a position RMSE of 7.13 m, compared to 41.29 m using non-differential measurements, and 87.74 m with GNSS-aided IMU

One Health – an Ecological and Evolutionary Framework for tackling Neglected Zoonotic Diseases

Understanding the complex population biology and transmission ecology of multihost parasites has been declared as one of the major challenges of biomedical sciences for the 21st century and the Neglected Zoonotic Diseases (NZDs) are perhaps the most neglected of all the Neglected Tropical Diseases (NTDs). Here we consider how multihost parasite transmission and evolutionary dynamics may affect the success of human and animal disease control programmes, particularly neglected diseases of the developing world. We review the different types of zoonotic interactions that occur, both ecological and evolutionary, their potential relevance for current human control activities, and make suggestions for the development of an empirical evidence base and theoretical framework to better understand and predict the outcome of such interactions. In particular, we consider whether preventive chemotherapy, the current mainstay of NTD control, can be successful without a One Health approach. Transmission within and between animal reservoirs and humans can have important ecological and evolutionary consequences, driving the evolution and establishment of drug resistance, as well as providing selective pressures for spill‐over, host switching, hybridizations and introgressions between animal and human parasites. Our aim here is to highlight the importance of both elucidating disease ecology, including identifying key hosts and tailoring control effort accordingly, and understanding parasite evolution, such as precisely how infectious agents may respond and adapt to anthropogenic change. Both elements are essential if we are to alleviate disease risks from NZDs in humans, domestic animals and wildlife

Tumoral CD105 is a novel independent prognostic marker for prognosis in clear-cell renal cell carcinoma

International audienceBackground: Angiogenesis is essential for tumour growth and metastasis. There are conflicting reports as to whether microvessel density (MVD) using the endothelial marker CD105 (cluster of differentiation molecule 105) in clear-cell renal cell carcinomas (ccRCC) is associated with prognosis. Recently, CD105 has been described as a RCC cancer stem cell marker.Methods: A total of 102 ccRCC were analysed. Representative tumour sections were stained for CD105. Vascularity (endothelial CD105) was quantified by MVD. The immunohistochemistry analysis detected positive (if present) or negative (if absent) CD105 tumoral staining. This retrospective population-based study was evaluated using Kaplan–Meier method, t-test and Cox proportional hazard model.Results: We found that the expression of endothelial CD105 (MVD) negatively correlated with nuclear grade (P<0.001), tumour stage (P<0.001) and Leibovitch score (P<0.001), whereas the expression of tumoral CD105 positively correlated with these three clinicopathological factors (P<0.001). In multivariate analysis, tumoral CD105 was found to be an independent predictor of poor overall survival (P=0.002).Conclusions: We have shown for the first time that tumoral CD105 is an independent predictive marker for death risk and unfavourable prognosis in patients with ccRCC after curative resection

The history of leishmaniasis

In this review article the history of leishmaniasis is discussed regarding the origin of the genus Leishmania in the Mesozoic era and its subsequent geographical distribution, initial evidence of the disease in ancient times, first accounts of the infection in the Middle Ages, and the discovery of Leishmania parasites as causative agents of leishmaniasis in modern times. With respect to the origin and dispersal of Leishmania parasites, the three currently debated hypotheses (Palaearctic, Neotropical and supercontinental origin, respectively) are presented. Ancient documents and paleoparasitological data indicate that leishmaniasis was already widespread in antiquity. Identification of Leishmania parasites as etiological agents and sand flies as the transmission vectors of leishmaniasis started at the beginning of the 20th century and the discovery of new Leishmania and sand fly species continued well into the 21st century. Lately, the Syrian civil war and refugee crises have shown that leishmaniasis epidemics can happen any time in conflict areas and neighbouring regions where the disease was previously endemic

Combined Angiogenesis and Proliferation Markers' Expressions as Long-Term Prognostic Factors in Renal Cell Cancer

Peer reviewe

IoT and anomaly detection for the iron ore mining industry

Thesis: S.M., Massachusetts Institute of Technology, Sloan School of Management, Operations Research Center, 2016.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references (pages 176-182).In the context of a world flooded with data, the Internet of Things (IoT) is exploding. This thesis considers the problem of applying IoT technology to the reduction of costs in the iron ore mining industry, to compensate for the iron ore price slumping observed over the past years. More specifically, we focused on improving the quality of the output in a data-driven iron ore concentration factory. In this plant, mined iron ore goes through a series of complex physical and chemical transformations so as to increase the concentration in iron and reduce the concentration in impurities such as silica. In this thesis, we developed an IoT infrastructure comprising of machines, a network of sensors, a database, a random forest prediction model, an algorithm for adjusting its cutoff parameter dynamically, and a predictive maintenance algorithm. It can preventively detect and maybe fix poor quality events in the iron ore concentration factory, improving the overall quality and decreasing costs. The random forest model was selected among other anomaly detection techniques. It is able, on an independent test data set, with an AUC of about 0.92, to detect 90% of the poor quality events, with a false positive rate of 23.02%, lowered by the dynamic cutoff algorithm. These methods can be applied to any factory in any industry, as long as it has a good infrastructure of sensors, providing sufficiently precise and frequent data.by Carl Elie Saroufim.S.M