Clinical trial failures (>99%) in Alzheimer's disease are in stark contrast to positive efficacy data in animals. We evaluated the correlation between animal and clinical efficacy outcomes ...(cognition) in Alzheimer's disease using data from registered drugs as well as interventions tested in phase II or III clinical trials for Alzheimer's disease.
We identified 20 interventions, which were tested in 208 animal studies in 63 different animal models. Clinical outcome was correlated with animal results in 58% of cases. But, individual animal models showed divergent results across interventions, individual interventions showed divergent results across animal models, and animal model outcomes were determined with 16 different methods.
This result is unsurprising due to poor external validity (what do we model) of the animal models. Although the animal models all share Alzheimer's disease symptoms, none represents the whole syndrome. Investigators did not motivate why one model was chosen over another, and did not consider the ways the disease phenomena were generated (spontaneous, (experimentally) induced or by genetic modification), or the species characteristics, which determine the outcomes. The explanation for the lack of correlation between animal and human outcomes can be manifold: the pathogenesis of Alzheimer's disease is not reflected in the animal model or the outcomes are not comparable.
Our conclusion is that currently no animal models exist which are predictive for the efficacy of interventions for Alzheimer's disease.
Results are presented for the first measurement of the double-polarization helicity asymmetry E for the η photoproduction reaction γ p → η p. Data were obtained using the FROzen Spin Target (FROST) ...with the CLAS spectrometer in Hall B at Jefferson Lab, covering a range of center-of-mass energy W from threshold to 2.15 GeV and a large range in center-of-mass polar angle. As an initial application of these data, the results have been incorporated into the J\"ulich model to examine the case for the existence of a narrow Ν* resonance between 1.66 and 1.70 GeV. The addition of these data to the world database results in marked changes in the predictions for the E observable using that model. As a result, further comparison with several theoretical approaches indicates these data will significantly enhance our understanding of nucleon resonances.
Uterine fibroids are the most common benign tumors in women, with abnormal uterine bleeding (AUB) as the main reported symptom. Additionally, an association between fibroids and infertility has been ...established, especially if the fibroid protrudes in the uterine cavity. Hormonal therapy is associated with side-effects and as well as hysterectomy, which is incompatible with a desire to conceive. To improve treatment, it is essential to unravel the etiology of fibroid-related symptoms. We aim to evaluate endometrial angiogenesis in women with fibroids, with and without AUB, and the influence of pharmaceutical therapies in these patients. Furthermore, we explore the possible role of altered angiogenesis in patients with fibroids and infertility. We performed a systematic review according to PRISMA-guidelines (PROSPERO: CRD42020169061), and included 15 eligible studies. Endometrial expression of vascular endothelial growth factor (VEGF) and adrenomedullin was increased in patients with fibroids. This suggests aberrant angiogenesis, potentially involving disturbed vessel maturation, resulting in immature and fragile vessels. Treatment with gonadotropin-releasing hormone agonist, ulipristal acetate, and continuous oral contraception pills reduced several angiogenic parameters, including VEGF. If infertile and fertile patients with fibroids were compared, a significant decreased expression of the bone morphogenetic protein/Smad-protein pathway was found, possibly caused by the increased expression of transforming growth factor-beta. For future therapeutic development, these different angiogenic pathways could be of interest as possible targets to treat fibroid-related symptoms.
We report on the first measurement of the differential cross section of ϕ-meson photoproduction for the d(γ,pK+K−)n exclusive reaction channel. The experiment was performed using a tagged-photon beam ...and the CEBAF Large Acceptance Spectrometer (CLAS) at Jefferson Lab. A combined analysis using data from the d(γ,pK+K−)n channel and those from a previous publication on coherent ϕ production on the deuteron has been carried out to extract the ϕ−N total cross section, σϕN. The extracted ϕ−N total cross section favors a value above 20 mb. This value is larger than the value extracted using vector-meson dominance models for ϕ photoproduction on the proton.
We present a state-of-the-art evaluation of the polarizability corrections--the inelastic nucleon corrections--to the hydrogen ground-state hyperfine splitting using analytic fits to the most recent ...data. We find a value Delta(pol)=1.3+/-0.3 ppm. This is 1-2 ppm smaller than the value of Delta(pol) deduced using hyperfine splitting data and elastic nucleon corrections obtained from modern form factor fits.
The cross section for coherent omega-meson photoproduction off the deuteron has been measured for the first time as a function of the momentum transfer t=(P-gamma - P-omega)(2) and photon energy ...E-gamma using the CLAS detector at the Thomas Jefferson National Accelerator Facility. The cross sections are measured in the energy range 1.4 < E-gamma < 3.4GeV. A model based on omega- N rescattering is consistent with the data at low and intermediate momentum transfer, vertical bar t vertical bar. For 2.8 < E-gamma < 3.4GeV, the total cross-section of omega - N scattering, based on fits within the framework of the Vector Meson Dominance model, is in the range of 30-40 mb.
MRI detectable and targeted quantum dots were developed. To that aim, quantum dots were coated with paramagnetic and pegylated lipids, which resulted in a relaxivity, r 1, of nearly 2000 mM-1s-1 per ...quantum dot. The quantum dots were functionalized by covalently linking αvβ3-specific RGD peptides, and the specificity was assessed and confirmed on cultured endothelial cells. The bimodal character, the high relaxivity, and the specificity of this nanoparticulate probe make it an excellent contrast agent for molecular imaging purposes.
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