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We present new absolute archaeointensity data from six archaeological sites situated in the Okayama Prefecture, Japan. The materials studied are well-dated fragments from pottery, ceramic coffins and haniwa artefacts. Their ages range from 160 AD to 675 AD, covering the Late Yayoi and Kofun periods. Rock magnetic experiments suggest the presence of magnetite and/or Ti-magnetite as the main carrier of the remanence, with a possible minor contribution of higher coercivity minerals. After thermal demagnetization experiments, the most magnetically stable samples were selected for archaeointensity analysis performed following the double-heating method proposed by Thellier and modified by Coe. Partial thermoremanent magnetization (pTRM) checks and pTRM tail-checks were performed for monitoring possible chemical alterations during heating. All measurements were corrected for both anisotropy and cooling-rate effects. Successful archaeointensity determinations, following rigorous selection criteria, were obtained for samples from all the investigated archaeological sites. Compared with literature data from Japan, the new high-quality data show significantly lower intensity values. They also reveal possible fast secular variation changes during the Late Yayoi period and very weak geomagnetic intensity field around 630 AD. Such values offer evidence of a possible recurrence of weak intensity field in East Asia, suggesting an ancient recurrence of the West Pacific Anomaly. The new data might change the archaeomagnetic field models interpretations in the area, even though more data are still necessary to better understand the secular variation in Japan and the temporal evolution of the geomagnetic field's behaviour in East Asia. [ABSTRACT FROM AUTHOR]

Purpose: As the COVID-19 pandemic forced most colleges and universities to go online, student health centers rapidly shifted to telehealth platforms without frameworks for virtual care provision. An urban student health center implemented a needs assessment involving unannounced standardized patients (USPs) to evaluate the integration of a new telehealth workflow and clinicians' virtual communication skills., Methods: From April to May 2021, USPs conducted two video visits with 12 primary care and four women's health clinicians (N = 16 clinicians; 32 visits). Cases included (1) a 21-year-old female presenting for birth control with a positive Patient Health Questionaire-9 and (2) a 21-year-old male, who vapes regularly, with questions regarding safe sex with men. Clinicians were evaluated using a checklist completed by the USP immediately following the visit and a systematic chart review of the electronic health record., Results: USP feedback indicates most clinicians received high ratings for general communication skills but may benefit from educational intervention in several key telemedicine skills. Clinicians struggled with using nonverbal signals to enrich communication (47% well done), acknowledging emotions (34% well done), and using video for information gathering (34% well done). Low rates of standard screenings (e.g., 63% administered the PHQ-2, <50% asked about alcohol use) suggested protocols for in-person care were not easily incorporated into telehealth practices, and clinicians may benefit from enhanced care team support. Performance reports were shared with clinicians and leadership postvisit., Discussion: Results suggest project design and implementation is scalable and feasible for use at other institutions, offering a structured methodology that can improve general student health care., (Copyright © 2024 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To identify design elements of clinical trials leading to US Food and Drug Administration approval of drugs for neurological diseases with and without orphan indications., Methods: We used publicly available information to identify approvals for drugs for neurological diseases with an orphan indication (n = 19) and compared them with recent approvals for drugs for neurological diseases without an orphan indication (n = 20). We identified "pivotal trials" from drug labels and drug approval packages, and assessed them on four elements of clinical trial design: control, blinding, randomization, and size., Results: All drugs for neurological diseases (100%) approved without an orphan indication included at least two randomized, double-blind, placebo-controlled trials. In comparison, 32% of drugs with an orphan indication had at least two such trials (p < 0.001) and 74% had at least one (p = 0.02). Thirty-three pivotal trials were conducted for the 19 drugs approved with an orphan indication. Of the 33 trials, 11 (33%) did not use a placebo control, 9 (27%) were not double blind, and 4 (12%) were not randomized. Drugs approved without an orphan indication had more pivotal trials per drug (3.8 vs 1.7 trials; p < 0.001) and a larger mean trial size (506 vs 164 trial participants; p < 0.001)., Interpretation: The US Food and Drug Administration has approved orphan drugs for neurological diseases without randomized, doubled-blind, placebo-controlled pivotal trials. As orphan drug development grows, demand will likely increase for alternative designs for conducting adequate and well-controlled studies to demonstrate drug efficacy.

During meiosis, double-strand breaks (DSBs) lead to crossovers, thought to arise from the resolution of double Holliday junctions (HJs) by an HJ resolvase. In Schizosaccharomyces pombe, meiotic crossovers are produced primarily through a mechanism requiring the Mus81-Eme1 endonuclease complex. Less is known about the processes that produces crossovers during the repair of DSBs in mitotic cells. We employed an inducible DSB system to determine the role of Rqh1-Top3 and Mus81-Eme1 in mitotic DSB repair and crossover formation in S. pombe. In agreement with the meiotic data, crossovers are suppressed in cells lacking Mus81-Eme1. And relative to the wild type, rqh1Delta cells show a fourfold increase in crossover frequency. This suppression of crossover formation by Rqh1 is dependent on its helicase activity. We found that the synthetic lethality of cells lacking both Rqh1 and Eme1 is suppressed by loss of swi5(+), which allowed us to show that the excess crossovers formed in an rqh1Delta background are independent of Mus81-Eme1. This result suggests that a second process for crossover formation exists in S. pombe and is consistent with our finding that deletion of swi5(+) restored meiotic crossovers in eme1Delta cells. Evidence suggesting that Rqh1 also acts downstream of Swi5 in crossover formation was uncovered in these studies. Our results suggest that during Rhp51-dependent repair of DSBs, Rqh1-Top3 suppresses crossovers in the Rhp57-dependent pathway while Mus81-Eme1 and possibly Rqh1 promote crossovers in the Swi5-dependent pathway.

Many questions remain about the process of DNA double strand break (DSB) repair by homologous recombination (HR), particularly concerning the exact function played by individual proteins and the details of specific steps in this process. Some recent studies have shown that RecQ DNA helicases have a function in HR. We studied the role of the RecQ helicase Rqh1 with HR proteins in the repair of a DSB created at a unique site within the Schizosaccharomyces pombe genome. We found that DSBs in rqh1(+) cells, are predominantly repaired by interchromosomal gene conversion, with HR between sister chromatids [sister-chromatid conversion (SCC)], occurring less frequently. In Deltarqh1 cells, repair by SCC is favored, and gene conversion rates slow significantly. When we limited the potential for SCC in Deltarqh1 cells by reducing the length of the G2 phase of the cell cycle, DSB repair continued to be predominated by SCC, whereas it was essentially eliminated in wild-type cells. These data indicate that Rqh1 acts to regulate DSB repair by blocking SCC. Interestingly, we found that this role for Rqh1 is independent of its helicase activity. In the course of these studies, we also found nonhomologous end joining to be largely faithful in S. pombe, contrary to current belief. These findings provide insight into the regulation of DSB repair by RecQ helicases.