Thrombolysis is an effective and safe therapy in stuck bileaflet mitral valves in the absence of high-risk thrombi

AbstractOBJECTIVESWe sought to evaluate the effectiveness and safety of thrombolytic therapy in stuck mitral bileaflet heart valves in the absence of high-risk thrombi.BACKGROUNDCurrent recommendations for the thrombolytic treatment of stuck prosthetic mitral valves are partially based on older valve models and inclusion of patients in whom high-risk thrombi were either ignored or not sought for. The feasibility and safety of thrombolysis in bileaflet models may be affected by the predilection of thrombi to catch the leaflet hinge.METHODSWe studied 12 consecutive patients (men/women = 5/7, age 58.8 ± 14.9 years) who experienced one or more episodes of stuck bileaflet mitral valve over a 33-month period and received thrombolytic therapy with streptokinase, urokinase or tissue-type plasminogen activator. Transesophageal echocardiography was performed in all patients. Patients with mobile or large (>5 mm) thrombi were excluded. Functional class at initial episode was I–II in 4 patients (33.3%) and III–IV in 8 patients (66.6%).RESULTSPatients receiving thrombolytic therapy achieved an overall 83.3% freedom from a repeat operation or major complications (95% confidence interval 51.6–97.9%). Minor bleeding occurred in three patients (25%) and allergic reaction in one (8.3%). Transient vague neurologic complaints, without subjective findings, occurred in four patients (33.3%). Three patients had one or more relapses within 5.2 ± 3.1 months from the previous episode, and readministration of thrombolytics was successful.CONCLUSIONSIn clinically stable patients with stuck bileaflet mitral valves and no high-risk thrombi, thrombolysis is highly successful and safe, both in the primary episode and in recurrence. The best thrombolytic regimen is yet to be established

Sagittarius A* Small Satellite Mission: Capabilities and Commissioning Preview

SSCI is leading a Defense Advanced Research Projects Agency (DARPA)-funded team launching a mission in June 2021, dubbed Sagittarius A*, to demonstrate key hardware and software technologies for on-orbit autonomy, to provide a software testbed for on-orbit developmental test & autonomous mission operations, and to reduce risk for future constellation-level mission autonomy and operations. In this paper, we present the system CONOPs and capabilities, system architectures, flight and ground software development status, and initial commissioning status. The system will fly on Loft Orbital’s YAM-3 shared LEO satellite mission, and includes SSCI’s onboard autonomy software suite running on an Innoflight CFC-400 processor with onboard Automatic Target Recognition (ATR). The autonomy payload has attitude control authority over the spacecraft bus and command authority of the imaging payload, and performs fully-autonomous onboard request handling, resource & task allocation, collection execution, ATR, and detection downlinking. The system is capable of machine-to -machine tip-and-cue from offboard cueing sources via cloud-based integrations. Requests for mission data are submitted to the satellite throughout its orbit from a tactical user level via a smartphone application, and ISR data products are downlinked and displayed at the tactical level on an Android Tactical Assault Kit (ATAK) smartphone. Follow-on software updates can be sent to the autonomy suite as over-the-air updates for on-orbit testing at any time during the on-orbit life of the satellite. Communications include GlobalStar inter-satellite communications for low rate task and status monitoring, and ground station links for payload data downloads. Planned demonstrations and opportunities will be discussed

On Synchronization in a Lattice Model of Pulse-Coupled Oscillators

We analyze the collective behavior of a lattice model of pulse-coupled oscillators. By means of computer simulations we find the relation between the intrinsic dynamics of each member of the population and their mutual interaction that ensures, in a general context, the existence of a fully synchronized regime. This condition turns out to be the same than the obtained for the globally coupled population. When the condition is not completely satisfied we find different spatial structures. This also gives some hints about self-organized criticality.Comment: 4 pages, RevTex, 1 PostScript available upon request, To appear in Phys. Rev. Let

The STRIPES Trial - Support to Rural India's Public Education System

Background Performance of primary school students in India lags far below government expectations, and major disparity exists between rural and urban areas. The Naandi Foundation has designed and implemented a programme using community members to deliver after-school academic support for children in over 1,100 schools in five Indian states. Assessments to date suggest that it might have a substantial effect. This trial aims to evaluate the impact of this programme in villages of rural Andhra Pradesh and will compare test scores for children in three arms: a control and two intervention arms. In both intervention arms additional after-school instruction and learning materials will be offered to all eligible children and in one arm girls will also receive an additional 'kit' with a uniform and clothes. Methods/Design The trial is a cluster-randomised controlled trial conducted in conjunction with the CHAMPION trial. In the CHAMPION trial 464 villages were randomised so that half receive health interventions aiming to reduce neonatal mortality. STRIPES will be introduced in those CHAMPION villages which have a public primary school attended by at least 15 students at the time of a baseline test in 2008. 214 villages of the 464 were found to fulfil above criteria, 107 belonging to the control and 107 to the intervention arm of the CHAMPION trial. These latter 107 villages will serve as control villages in the STRIPES trial. A further randomisation will be carried out within the 107 STRIPES intervention villages allocating half to receive an additional kit for girls on the top of the instruction and learning materials. The primary outcome of the trial is a composite maths and language test score. Discussion The study is designed to measure (i) whether the educational intervention affects the exam score of children compared to the control arm, (ii) if the exam scores of girls who receive the additional kit are different from those of girls living in the other STRIPES intervention arm. One of the goals of the STRIPES trial is to provide benefit to the controls of the CHAMPION trial. We will also conduct a cost-benefit analysis in which we calculate the programme cost for 0.1 standard deviation improvement for both intervention arms

Reticular dysgenesis-associated AK2 protects hematopoietic stem and progenitor cell development from oxidative stress.

Adenylate kinases (AKs) are phosphotransferases that regulate the cellular adenine nucleotide composition and play a critical role in the energy homeostasis of all tissues. The AK2 isoenzyme is expressed in the mitochondrial intermembrane space and is mutated in reticular dysgenesis (RD), a rare form of severe combined immunodeficiency (SCID) in humans. RD is characterized by a maturation arrest in the myeloid and lymphoid lineages, leading to early onset, recurrent, and overwhelming infections. To gain insight into the pathophysiology of RD, we studied the effects of AK2 deficiency using the zebrafish model and induced pluripotent stem cells (iPSCs) derived from fibroblasts of an RD patient. In zebrafish, Ak2 deficiency affected hematopoietic stem and progenitor cell (HSPC) development with increased oxidative stress and apoptosis. AK2-deficient iPSCs recapitulated the characteristic myeloid maturation arrest at the promyelocyte stage and demonstrated an increased AMP/ADP ratio, indicative of an energy-depleted adenine nucleotide profile. Antioxidant treatment rescued the hematopoietic phenotypes in vivo in ak2 mutant zebrafish and restored differentiation of AK2-deficient iPSCs into mature granulocytes. Our results link hematopoietic cell fate in AK2 deficiency to cellular energy depletion and increased oxidative stress. This points to the potential use of antioxidants as a supportive therapeutic modality for patients with RD

Real-time observation of multiexcitonic states in ultrafast singlet fission using coherent 2D electronic spectroscopy.

Singlet fission is the spin-allowed conversion of a spin-singlet exciton into a pair of spin-triplet excitons residing on neighbouring molecules. To rationalize this phenomenon, a multiexcitonic spin-zero triplet-pair state has been hypothesized as an intermediate in singlet fission. However, the nature of the intermediate states and the underlying mechanism of ultrafast fission have not been elucidated experimentally. Here, we study a series of pentacene derivatives using ultrafast two-dimensional electronic spectroscopy and unravel the origin of the states involved in fission. Our data reveal the crucial role of vibrational degrees of freedom coupled to electronic excitations that facilitate the mixing of multiexcitonic states with singlet excitons. The resulting manifold of vibronic states drives sub-100 fs fission with unity efficiency. Our results provide a framework for understanding singlet fission and show how the formation of vibronic manifolds with a high density of states facilitates fast and efficient electronic processes in molecular systems.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/nchem.237