Quasifree photoproduction of eta mesons off nucleons bound in the deuteron has been measured with the CBELSA/TAPS detector for incident photon energies up to 2.5 GeV at the Bonn ELSA accelerator. The ...eta mesons have been detected in coincidence with recoil protons and recoil neutrons, which allows a detailed comparison of the quasifree n(gamma,eta)n and p(gamma,eta)p reactions. The excitation function for eta production off the neutron shows a pronounced bumplike structure at W=1.68 GeV (E{gamma} approximately 1 GeV), which is absent for the proton.
Abstract
Background
Catheter-directed thrombolysis (CDT) can accelerate relief of the right ventricle overload secondary to acute pulmonary embolism (PE). The effectiveness and safety of CDT, also in ...relation to dose, duration, and different devices, are still a matter of debate.
Purpose
We conducted a systematic review and meta-analysis to assess effectiveness and safety of CDT for intermediate- and high-risk acute PE.
Methods
We systematically searched PubMed, Web of Science and CENTRAL (inception-December 2022) and selected randomized controlled trials (RCTs), observational studies, and epidemiological analysis (DRG-based, nationwide studies), focusing on standard CDT (sCDT) vs. ultrasound-assisted catheter-directed thrombolysis (USAT) for intermediate- and high-risk acute PE, according to European Society of Cardiology definition. We obtained pooled estimate rates for bleeding (intracranial and major), in-hospital/30-day fatality rate, and estimated the early improvement of several hemodynamic parameters (i.e. right/left ventricle RV/LV ratio, pulmonary artery pressure PAP) and long-term course.
Results
Overall, 58 studies with 37,496 patients (mean age 60 years) were included. The pooled intracranial bleeding rate was 0.15% (95%CI: 0-0.58%) in trials and cohort studies, and 0.87% (95%CI: 0.44-1.42%) in epidemiological studies; Fig. 1. Randomized trials comparing CDT vs. anticoagulation alone reported neither intracranial nor fatal bleeding events. In trials and cohort studies, higher rates of major bleedings were observed with longer (4.5%; 95%CI: 2.4-7.1%) vs. shorter (0.7%, 95%CI: 0-2.2%) treatment duration (p=0.01), irrespective of the dose; Fig. 2. Longer CDT regimens were associated with a high fatality rate of 2.8% (95%CI: 1.5-4.2%) vs. 0.1% (95%CI: 0-1.1%) with shorter CDT treatment (<0.01), disregarding the lytic dose; Fig. 2. All early hemodynamic and radiological outcomes assessed in available studies improve after CDT regardless of dose, duration, and type of device. However, data on the long-term course of PE after CDT has been rarely reported in literature.
Conclusions
The available evidence supports the notion that CDT strategies may represent a safe option for reversing right ventricular dysfunction due to acute PE. Overall, the reported rate of intracranial bleeding was below 1%. Patients exposed to longer CDT regimens had a higher incidence of major bleeding and fatality. Randomised trials with clinical outcomes are necessary to truly establish optimal patient selection and CDT protocol.Prevalence of intracranial bleedingOutcomes in RCTs and cohort studies
The aim of this paper is to describe a conceptual framework for how to consider health equity in the Grading Recommendations Assessment and Development Evidence (GRADE) guideline development process.
...Consensus-based guidance developed by the GRADE working group members and other methodologists.
We developed consensus-based guidance to help address health equity when rating the certainty of synthesized evidence (i.e., quality of evidence). When health inequity is determined to be a concern by stakeholders, we propose five methods for explicitly assessing health equity: (1) include health equity as an outcome; (2) consider patient-important outcomes relevant to health equity; (3) assess differences in the relative effect size of the treatment; (4) assess differences in baseline risk and the differing impacts on absolute effects; and (5) assess indirectness of evidence to disadvantaged populations and/or settings.
The most important priority for research on health inequity and guidelines is to identify and document examples where health equity has been considered explicitly in guidelines. Although there is a weak scientific evidence base for assessing health equity, this should not discourage the explicit consideration of how guidelines and recommendations affect the most vulnerable members of society.
3-Hydroxy-4-carboxyalkylamidino-5-arylamino-isothiazoles were discovered as potent in vitro MEK Inhibitors
3-Hydroxy-4-carboxyalkylamidino-5-arylamino-isothiazoles were discovered as potent in vitro ...MEK1 inhibitors.
The feasibility of using a sensitive polymerase chain reaction (PCR) to evaluate malaria vaccines in small group sizes was tested in 102 adult Gambian volunteers who received either the malaria ...vaccine regimen FP9 ME-TRAP/MVA ME-TRAP or rabies vaccine. All volunteers received the antimalarial drugs primaquine and Lapdap plus artesunate to eliminate malaria parasites. Volunteers in a further group received an additional single treatment with sulfadoxine-pyrimethamine (SP) to prevent new infections. There was substantially lower T-cell immunogenicity than in previous trials with this vaccine regimen and no protection against infection in the malaria vaccine group. Using the primary endpoint of 20 parasites per mL, no difference was found in the prevalence of low-level infections in volunteers who received SP compared with those who did not, indicating that SP did not reduce the incidence of very low-density infection. However, SP markedly reduced the incidence of higher density infections. These findings support the feasibility and potential of this approach to screen pre-erythrocytic vaccines for efficacy against infection in small numbers of vaccinees in endemic areas.
We report the final measurement of the neutrino oscillation parameters Δm322 and sin2 θ23 using all data from the MINOS and MINOS+ experiments. These data were collected using a total exposure of ...23.76 × 1020 protons on target producing νμ and νμ beams and 60.75 kt yr exposure to atmospheric neutrinos. The measurement of the disappearance of νμ and the appearance of νe events between the Near and Far detectors yields ... and ... at 68% C.L. for normal (inverted) hierarchy. (ProQuest: ... denotes formulae omited.).
A heterologous prime‐boost strategy has been developed to potently induce T cell responses to pre‐erythrocytic malaria antigens. Efficacy in the field is likely to depend on both peak immunogenicity ...and the durability of responses. To improve both immunogenicity and durability of responses, 54 adult males from a malaria endemic area were immunized with different vaccination regimens, systematically varying antigenic insert and the number and sequence of component vaccinations. The component vaccinations were recombinant attenuated viruses, either fowlpox (FP) 9 or modified vaccinia virus Ankara (MVA). These were recombinant for either of two pre‐erythrocytic malaria antigens (multiple epitope‐thrombospondin‐related adhesion protein, ME‐TRAP, or circumsporozoite antigen (CS). ELISPOT assays were used to measure the effector and resting memory T cell responses. Sequence, antigen insert and number of vaccinations influenced immunogenicity, but the novel alternating vector immunizations generated the largest resting memory T cell populations. Effector responses were maintained at 84% of the peak response after 270 days. This durability of response is unprecedented. Classical prime‐boost vaccination responses were at 5% of the peak after 270 days. Vaccines administered by heterologous prime‐boost regimes are being developed for diverse pathogens and cancer. These data suggest these vaccines should also be administered by alternating vector regimens in clinical development.
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