A Child with Resistance to Thyroid Hormone without Thyroid Hormone Receptor Gene Mutation: A 20-Year Follow-Up

We report here the 20-year follow-up study of a male subject diagnosed at 15 months of age as a sporadic case of pituitary resistance to thyroid hormone on the combination of clinical hyperthyroidism, elevated serum thyroid hormone (TH) levels and inappropriate thyrotropin (TSH). On d-thyroxine (D-T4) therapy from 30 months of age to 12.5 years, hyperactivity and hyperthyroid signs and symptoms as well as growth abnormalities improved, serum l-thyroxine (L-T4) enantiomer normalized, and basal and stimulated TSH decreased significantly without complete suppression. After 8 years off D-T4, at 20 years of age, clinical status was normal despite persisting high TH levels and inappropriate TSH. Evolution of serum markers of TH action and echocardiography measurements followed up from 15 months to 20 years of age either in basal condition or on triiodothyronine (T3), as well as the sequential determination of bone mineral density suggest differences in the tissue responses to T3: normal in bone with a high remodelling rate, heterogeneity for various hepatic markers, and decreased at heart level. No mutations were found in the coding sequence of TRβ1, TRβ2, TRα1, RXRγ, SMRT, NCoR1, and NCoA1. In this patient the putative long-term effects of the persisting high bone resorption are unknown

New dry friction model with load- and velocity- dependence and dynamic identification of multi-dof robots

International audience— Usually, the joint transmission friction model for robots is composed of a viscous friction force and of a constant dry sliding friction force. However, according to the Coulomb law, the dry friction force depends linearly on the load driven by the transmission, which has to be taken into account for robots working with large variation of the payload or inertial and gravity forces. Moreover, for robots actuating at low velocity, the Stribeck effect must be taken into account. This paper proposes a new inverse dynamic identification model for n degrees of freedom (dof) serial robot, where the dry sliding friction force is a linear function of both the dynamic and the external forces, with a velocity-dependent coefficient. A new sequential identification procedure is carried out. At a first step, the friction model parameters are identified for each joint (1 dof), moving one joint at a time (this step has been validated in [23]). At a second step, these values are fixed in the n dof dynamic model for the identification of all robot inertial and gravity parameters. For the two steps, the identification concatenates all the joint data collected while the robot is tracking planned trajectories with different payloads to get a global least squares estimation of inertial and new friction parameters. An experimental validation is carried out with an industrial 3 dof robot

Pressure-stabilized fixed-stress iterative solutions of compositional poromechanics

We consider the numerical behavior of the fixed-stress splitting method for coupled poromechanics as undrained regimes are approached. We explain that pressure stability is related to the splitting error of the scheme, not the fact that the discrete saddle point matrix never appears in the fixed-stress approach. This observation reconciles previous results regarding the pressure stability of the splitting method. Using examples of compositional poromechanics with application to geological CO$_2$ sequestration, we see that solutions obtained using the fixed-stress scheme with a low order finite element-finite volume discretization which is not inherently inf-sup stable can exhibit the same pressure oscillations obtained with the corresponding fully implicit scheme. Moreover, pressure jump stabilization can effectively remove these spurious oscillations in the fixed-stress setting, while also improving the efficiency of the scheme in terms of the number of iterations required at every time step to reach convergence

New perspectives in the pathophysiology and treatment of affective disorders: the role of melatonin and serotonin

Более 40 лет в области исследований патогенеза депрессии и разработки адекватных препаратов для эффективной терапии этого расстройства доминировала моноаминовая гипотеза, предполагающая в основе депрессии дисбаланс функции серотонина, норадреналина и, возможно, дофамина. Хотя эти моноаминовые нейротрансмиттеры, роль которых обсуждается в данной публикации, несомненно, участвуют в патогенезе депрессии, их дефицит — лишь часть истории, так как для полного объяснения механизмов депрессии необходимо также учитывать другие нарушения вне рамок дисбаланса моноаминов. Существует явная потребность в более эффективных препаратах с улучшенной переносимостью и более быстрым действием. Разработка новых антидепрессантов на основании механизмов, не связанных с моноаминовой гипотезой, представляется более перспективной. Сегодня повышенное внимание уделяется связи аффективных расстройств, включая и депрессию, с аномальными изменениями в циркадианных ритмах. В этой публикации рассматривается роль мелатонина и его рецепторов при депрессии, а также данные по недавно разработанному антидепрессанту с подтвержденной клинической эффективностью — Вальдоксану. Этот препарат, обладающий свойствами агониста мелатонина и антагониста 5-НТ2С-рецепторов, является предвестником нового концептуального подхода к терапии депрессии

Bivalirudin started during emergency transport for primary PCI.

BACKGROUND: Bivalirudin, as compared with heparin and glycoprotein IIb/IIIa inhibitors, has been shown to reduce rates of bleeding and death in patients undergoing primary percutaneous coronary intervention (PCI). Whether these benefits persist in contemporary practice characterized by prehospital initiation of treatment, optional use of glycoprotein IIb/IIIa inhibitors and novel P2Y12 inhibitors, and radial-artery PCI access use is unknown. METHODS: We randomly assigned 2218 patients with ST-segment elevation myocardial infarction (STEMI) who were being transported for primary PCI to receive either bivalirudin or unfractionated or low-molecular-weight heparin with optional glycoprotein IIb/IIIa inhibitors (control group). The primary outcome at 30 days was a composite of death or major bleeding not associated with coronary-artery bypass grafting (CABG), and the principal secondary outcome was a composite of death, reinfarction, or non-CABG major bleeding. RESULTS: Bivalirudin, as compared with the control intervention, reduced the risk of the primary outcome (5.1% vs. 8.5%; relative risk, 0.60; 95% confidence interval [CI], 0.43 to 0.82; P=0.001) and the principal secondary outcome (6.6% vs. 9.2%; relative risk, 0.72; 95% CI, 0.54 to 0.96; P=0.02). Bivalirudin also reduced the risk of major bleeding (2.6% vs. 6.0%; relative risk, 0.43; 95% CI, 0.28 to 0.66; P<0.001). The risk of acute stent thrombosis was higher with bivalirudin (1.1% vs. 0.2%; relative risk, 6.11; 95% CI, 1.37 to 27.24; P=0.007). There was no significant difference in rates of death (2.9% vs. 3.1%) or reinfarction (1.7% vs. 0.9%). Results were consistent across subgroups of patients. CONCLUSIONS: Bivalirudin, started during transport for primary PCI, improved 30-day clinical outcomes with a reduction in major bleeding but with an increase in acute stent thrombosis. (Funded by the Medicines Company; EUROMAX ClinicalTrials.gov number, NCT01087723.)