Shortages of new therapeutics to treat coronavirus disease (COVID-19) have forced clinicians, public health officials, and health systems to grapple with difficult questions about how to fairly allocate potentially life-saving treatments when there are not enough for all patients in need (1). Shortages have occurred with remdesivir, tocilizumab, monoclonal antibodies, and the oral antiviral Paxlovid (2) -/- Ensuring equitable allocation is especially important in light of the disproportionate burden experienced during the COVID-19 pandemic by disadvantaged groups, including Black, Hispanic/Latino and (...) Indigenous communities, individuals with certain disabilities, and low-income persons. However, many health systems have resorted to first-come, first-served approaches to allocation, which tend to disadvantage individuals with barriers in access to care (3). There is mounting evidence of racial, ethnic, and socioeconomic disparities in access to medications for COVID-19 (4, 5). -/- One potential method to promote equitable allocation is to use a weighted lottery, which is an allocation strategy that gives all eligible patients a chance to receive the scarce treatment while also allowing the assignment of higher or lower chances according to other ethical considerations (6). We sought to assess the feasibility of implementing a weighted lottery to allocate scarce COVID-19 medications in a large U.S. health system and to determine whether the weighted lottery promotes equitable allocation. (shrink)

In list-method directed forgetting, reexposure to forgotten List 1 items has been shown to reduce directed forgetting. proposed that reexposure to a few List 1 items only during a direct test of memory reinstates the entire List 1 episode. In the present experiments, part-list reexposure in the context of indirect as well as direct memory tests reduced directed forgetting. Directed forgetting was reduced when 50% or more of the items were reexposed, and was intact when only 25% were reexposed. Furthermore, (...) part-list reexposure appeared to reinstate only reexposed items-not the entire List 1 episode. (shrink)

0-categorical o-minimal structures were completely described by Pillay and Steinhorn 565–592), and are essentially built up from copies of the rationals as an ordered set by ‘cutting and copying’. Here we investigate the possible structures which an 0-categorical weakly o-minimal set may carry, and find that there are some rather more interesting examples. We show that even here the possibilities are limited. We subdivide our study into the following principal cases: the structure is 1-indiscernible, in which case all possibilities are (...) classified up to binary structure; the structure is 2-indiscernible, classified up to ternary structure; the structure is 3-indiscernible, in which case we show that it is k-indiscernible for every finite k. We also make some remarks about the possible structures of higher arities which an 0-categorical weakly o-minimal structure may carry. (shrink)

The FDA's new table of surrogate endpoints used for drug approvals is an important step forward for overseeing the use of biomarkers in clinical trials. Nevertheless, we present several ways in which the table can be improved.

Le temps est un grand maître en médecine. Il fait évoluer la maladie, le malade et sa relation avec le médecin. Il revient à ce dernier d'en prendre la mesure pour la maîtriser et l'exploiter plutôt que de s'en laisser dominer. C'est ce que l'auteur fait approcher par petites touches au fil d'une cinquantaine de réflexions puisées dans son expérience et ses lectures, alimentés de données parfois dérangeantes. Elles doivent aider à gérer une denrée précieuse, d'une manière simple, mais qui (...) ne va pas toujours de soi et peut contredire un bon sens élémentaire. Il en va de la qualité d'une pratique médicale et des satisfactions que patients comme soignants peuvent en retirer, en choisissant plutôt qu'en subissant. (shrink)

Context. The identification of the sources that reionized the Universe and their specific contribution to this process are key missing pieces of our knowledge of the early Universe. Faint star-forming galaxies may be the main contributors to the ionizing photon budget during the epoch of reionization, but their escaping photons cannot be detected directly due to inter-galactic medium opacity. Hence, it is essential to characterize the properties of faint galaxies with significant Lyman continuum photon leakage up to z 4 to (...) define indirect indicators allowing analogues to be found at the highest redshift. Aims. Long gamma-ray bursts explode typically in star-forming regions of faint, star-forming galaxies. Through LGRB afterglow spectroscopy it is possible to detect directly LyC photons. Our aim is to use LGRBs as tools to study LyC leakage from faint, star-forming galaxies at high redshift. Methods. Here we present the observations of LyC emission in the afterglow spectra of GRB 191004B at z = 3:5055, together with those of the other two previously known LyC-emitting LGRB, to determine their LyC escape fraction and compare their properties. Results. From the afterglow spectrum of GRB 191004B we determine a neutral hydrogen column density at the LGRB redshift of og =17:2 0:15, and negligible extinction. The only metal absorption lines detected are C iv and Si iv. In contrast to GRB 050908 and GRB 060607A, the host galaxy of GRB 191004B displays significant Ly emission. From its Ly emission and the non-detection of Balmer emission lines we constrain its star-formation rate to 1 SFR 4:7 M yr. 1. We fit the Ly emission with a shell model and find parameters values consistent with the observed ones. The absolute LyC escape fractions we find for GRB 191004B, GRB 050908 and GRB 060607A are of 0:35+0:10.0:11, 0:08+0:05.0:04 and :20+0:05.0:05, respectively. We compare the LyC escape fraction of LGRBs to the values of other LyC emitters found from the literature, showing that LGRB afterglows can be powerful tools to study LyC escape for faint high-redshift star-forming galaxies. Indeed we could push LyC leakage studies to much higher absolute magnitudes. The host galaxies of the three LGRB presented here have all M1600 >.19:5 mag, with the GRB 060607A host at M1600 >.16 mag. LGRB hosts may therefore be particularly suitable for exploring the ionizing escape fraction in galaxies that are too faint or distant for conventional techniques. Furthermore the time investment is very small compared to galaxy studies. (shrink)

High-spin states have been studied in Pr-135(59), populated through the Cd-116(Na-23,4n) reaction at 115 MeV, using the Gammasphere gamma-ray spectrometer. The negative-parity yrast band has been significantly extended to spin similar to 45 (h) over bar and excitation energy 21.5 MeV, showing evidence for several rotational alignments. The positive-parity yrast band of Ce-135(58), populated through the p4n channel of this reaction, was also populated to spin similar to 38 (h) over bar and excitation energy 18 MeV. Cranking calculations indicate that (...) these nuclei are soft with respect to the triaxiality parameter gamma and that several competing nuclear shapes occur at high spin. (shrink)

Medium- and high-spin states of Pr-134 were populated using the Cd-116(Na-23, 5n) reaction and studied with the GAMMASPHERE spectrometer. Several new bands have been found in this nucleus, one of them being linked to the previously observed chiral-candidate twin-band structure. The ground state of Pr-134 could be determined through establishing a level structure that connects the two previously known long-lived isomeric states. Unambiguous spin-parity assignments for the excited states could be performed based on the known 2(-) spin-parity of the ground (...) state combined with the present experimental data. Intrinsic single-particle configurations have been assigned to the newly observed bands on the basis of the measured B(M1)/B(E2) ratios, alignments, band-crossing frequencies, bandhead spins, the observed single-particle configurations in the neighboring nuclei, and taking into account the predictions of total Routhian surface and tilted-axis cranking calculations. (shrink)

jild-i 1. Az ʻAbd al-Ḥamīd Kātib (59 Sh.) tā Abū al-Ḥasan Masʻūdī (336 Sh.) -- jild-i 2. Az Abū al-Ḥasan ʻĀmirī (291 Sh.) tā Abū al-Faz̤l Bayhaqī (465 Sh.) -- jild-i 3. Az Nāṣir Khusraw (383 Sh.) tā Sadīd al-Dīn ʻAwfī (616 Sh.) -- jild-i 4. Az Najm al-Dīn Rāzī (553 Sh.) tā Fakhr al-Muḥaqqiqīn (748 Sh.) -- jild-i 5. Az ʻUbayd Zākānī (670 Sh.) tā Jalāl al-Dīn Sayūṭī (884 Sh.) -- jild-i 6. Az Rūzbihān Khunjī (825 Sh.) tā Shaykh (...) Ḥurr ʻĀmilī (1071 Sh.) -- jild-i 7. Az ʻAlāmah Majlisī (1006 Sh.) tā Muḥammad Bāqir Shafaq (1223 Sh.) -- jild-i 8. Az Muḥammad Ṣādiq Marvazī (1147 Sh.) tā Mīrzā Fatḥʻalī Ākhūndzādah (1289 Sh.) -- jild-i 9. Az Mīrzā-yi Shīrāzī Avval (1194 Sh.) tā Ākhūnd Khurāsānī (1290 Sh.) -- jild-i 10. Az ʻAbd Allāh Māzandarānī (1219 Sh.) tā Saʻd Zaghlūl (1306 Sh.) -- jild-i 11. Az ʻImād al-ʻUlamāʼ Khalkhālī (1237 Sh.) tā ʻAbd al-ʻAzīz S̲aʻālibī (1323 Sh.) -- jild-i 12. Az Āyat Allāh Burūjirdī (1254 Sh.) tā Muḥammad Amīn Rasūlʹzādah (1333 Sh.) -- jild-i 13. Az ʻAbd al-Karīm Zanjānī (1263 Sh.) tā Amīn al-Ḥusaynī (1353 Sh.) -- jild-i 14. Az Jamālzādah (1274 Sh.) tā Mahdī Bāzargān (1373) -- jild-i 15. Az Muḥammad Ḥamīd Allāh (1286 Sh.) tā Muṭahharī (1358 Sh.) -- jild-i 16. Az Farīdūn Ādamīyat (1299 Sh.) tā Muṣṭafá Khumaynī (1356 Sh.) -- jild-i 17. Az Samīr Amīn (1310 Sh.) tā Ḥasan Ḥanafī -- jild-i 18. Az Sayyid Muḥammad Bāqir Ṣadr (1314 Sh.) tā Rāshid al-Ghanūshī -- jild-i 19. Az ʻAlī Awmlīl (1321 Sh.) tā Ṭāriq Ramaz̤ān. (shrink)

Cyclin-dependent kinase 5 has been implicated in Alzheimer's disease pathogenesis. Here, we demonstrate that overexpression of p25, an activator of cdk5, led to increased levels of BACE1 mRNA and protein in vitro and in vivo. A p25/cdk5 responsive region containing multiple sites for signal transducer and activator of transcription was identified in the BACE1 promoter. STAT3 interacts with the BACE1 promoter, and p25-overexpressing mice had elevated levels of pSTAT3 and BACE1, whereas cdk5-deficient mice had reduced levels. Furthermore, mice with a (...) targeted mutation in the STAT3 cdk5 responsive site had lower levels of BACE1. Increased BACE levels in p25 overexpressing mice correlated with enhanced amyloidogenic processing that could be reversed by a cdk5 inhibitor. These data demonstrate a pathway by which p25/cdk5 increases the amyloidogenic processing of APP through STAT3-mediated transcriptional control of BACE1 that could have implications for AD pathogenesis. (shrink)