641 research outputs found

    Baryogenesis and gravity waves from a UV-completed electroweak phase transition

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    We study gravity wave production and baryogenesis at the electroweak phase transition in a real singlet scalar extension of the Standard Model, including vectorlike top partners, to generate the CP violation needed for electroweak baryogenesis (EWBG). The singlet makes the phase transition strongly first order through its coupling to the Higgs boson, and it spontaneously breaks CP invariance through a dimension-five contribution to the top quark mass term, generated by integrating out the heavy top quark partners. We improve on previous studies by incorporating updated transport equations, compatible with large bubble wall velocities. The wall speed and thickness are computed directly from the microphysical parameters rather than treating them as free parameters, allowing for a first-principles computation of the baryon asymmetry. The size of the CP-violating dimension-five operator needed for EWBG is constrained by collider, electroweak precision, and renormalization group running constraints. We identify regions of parameter space that can produce the observed baryon asymmetry or observable gravitational wave (GW) signals. Contrary to standard lore, we find that for strong deflagrations, the efficiencies of large baryon asymmetry production and strong GW signals can be positively correlated. However, we find the overall likelihood of observably large GW signals to be smaller than estimated in previous studies. In particular, only detonation-type transitions are predicted to produce observably large gravitational waves.Peer reviewe

    Risk of SARS-CoV-2 Transmission During Flexible Laryngoscopy: A Systematic Review.

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    IMPORTANCE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reportedly infected otolaryngologists disproportionately in the early parts of the coronavirus disease 2019 pandemic. Recommendations from national and international health organizations suggest minimizing the use of flexible laryngoscopy as a result. OBJECTIVE: To review evidence on the risks of aerosolization and transmission of SARS-CoV-2 from patients to health care personnel during endoscopy of the upper aerodigestive tract. EVIDENCE REVIEW: A comprehensive review of literature was performed on April 19, 2020, using the PubMed/MEDLINE (1966-April 2020), Embase (1975-April 2020), and Web of Science (1900-April 2020) databases. All English-language primary research studies were included if they assessed the transmission of SARS-CoV-2 or SARS-CoV-1 during procedures in the upper aerodigestive tract. The primary outcome measure was disease transmission among health care workers. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for accuracy of reporting. FINDINGS: The queries for SARS-CoV-2 and SARS-CoV-1 identified 6 articles for systematic review. No studies included in this review provided data for SARS-CoV-2 transmission during flexible laryngoscopy. A total of 204 of 1264 health care workers (16.1%) had procedure-specific infections of SARS-CoV-1 or SARS-CoV-2. Among those, 53 of 221 (24.0%) were exposed during intubation, 1 of 15 (6.7%) during bronchoscopy, and 1 of 1 (100%) during endoscopy-assisted intubation. CONCLUSIONS AND RELEVANCE: A substantial lack of research precludes formal conclusions about the safety of flexible laryngoscopy and transmission of SARS-CoV-2 from patients to health care workers. The use of appropriate precautionary measures and personal protective equipment appears to reduce the risk of transmission. Given the uncertainty in transmission and the known benefits of safety precautions, upper airway endoscopy may be reasonable to perform if precautionary steps are taken

    The wave equation on singular space-times

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    We prove local unique solvability of the wave equation for a large class of weakly singular, locally bounded space-time metrics in a suitable space of generalised functions.Comment: Latex, 19 pages, 1 figure. Discussion of class of metrics covered by our results and some examples added. Conclusion more detailed. Version to appear in Communications in Mathematical Physic

    Volume Comparison for Hypersurfaces in Lorentzian Manifolds and Singularity Theorems

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    We develop area and volume comparison theorems for the evolution of spacelike, acausal, causally complete hypersurfaces in Lorentzian manifolds, where one has a lower bound on the Ricci tensor along timelike curves, and an upper bound on the mean curvature of the hypersurface. Using these results, we give a new proof of Hawking's singularity theorem.Comment: 15 pages, LaTe

    Supervisor trainees' and their supervisors' perceptions of attainment of knowledge and skills. An empirical evaluation of a psychotherapy supervisor training programme

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    Objectives. This study aimed to evaluate the success of a two-year, part-time training programme for psychotherapy supervisors. A second aim was to examine factors that might contribute to perceived knowledge and skills attainment during the training course. Design. This is a naturalistic, longitudinal study where several measures are used to examine group process and outcome. Methods. Supervisor trainees’ (n=21) and their facilitators’ (n=6) ratings of learning (knowledge and skills), relations to the supervisor and supervision group, usage of the group, and supervisor style were completed at three time points. Results. The findings suggested that both trainees and their supervisors perceived that the trainees attained a substantial amount of knowledge and skills during the course. In accordance with the literature and expectations, the regression analysis suggested a strong negative association between a strong focus on group processes in the initial and middle phases of the training and perceived knowledge and skills attainment in the final phase of the training. The expected, positive role of relations among trainees in the supervision group in the first half of the training and perceived knowledge and skills attainment in the final part of the training was obtained, whilst the hypothesized significance of the relationship between trainee and supervisor did not receive support. Conclusions The supervisory course seemed to provide a training that allowed trainees to attain knowledge and skills that are necessary for psychotherapy supervisors. The results of this pilot study also emphasize the need of more research on learning in the context of group supervision in psychotherapy

    Secondary somatic mutations restoring RAD51C and RAD51D associated with acquired resistance to the PARP inhibitor rucaparib in high-grade ovarian carcinoma

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    High-grade epithelial ovarian carcinomas (OC) containing mutated BRCA1 or BRCA2 (BRCA1/2) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and poly(ADP-ribose) polymerase inhibitors (PARPi), while restoration of HR function due to secondary mutations in BRCA1/2 has been recognized as an important resistance mechanism. We sequenced core HR pathway genes in 12 pairs of pre-treatment and post-progression tumor biopsy samples collected from patients in ARIEL2 Part 1, a phase 2 study of the PARPi rucaparib as treatment for platinum-sensitive, relapsed OC. In six of 12 pre-treatment biopsies, a truncation mutation in BRCA1, RAD51C or RAD51D was identified. In five of six paired post-progression biopsies, one or more secondary mutations restored the open reading frame. Four distinct secondary mutations and spatial heterogeneity were observed for RAD51C. In vitro complementation assays and a patient-derived xenograft (PDX), as well as predictive molecular modeling, confirmed that resistance to rucaparib was associated with secondary mutations

    SENP1 participates in the dynamic regulation of Elk-1 SUMOylation

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    The modification of proteins with SUMO (small ubiquitin-related modifier) plays an important role in determining their functional properties. Importantly though, SUMOylation is a highly dynamic process enabling transient responses to be elicited. This dynamism is controlled by two competing conjugating and deconjugating activities. The latter activity is mediated by the SENP [SUMO1/sentrin/SMT3 (suppressor of mif two 3 homologue 1)-specific peptidase] family of SUMO-specific proteases. The transcription factor Elk-1 [ETS (E twenty-six)-like 1] undergoes rapid de-SUMOylation following cellular stimulation with growth factors, and this contributes to its conversion from a SUMO-dependent repressor into a potent transcriptional activator. In the present study we demonstrate an important role for SENP1 in the de-SUMOylation of Elk-1, and therefore an integral role in determining the Elk-1-dependent transcriptional programme. Among the SENPs, Elk-1 preferentially forms a complex with SENP1. This preferential binding is reflected by the higher efficiency of SENP1 in promoting Elk-1 transactivation. Moreover, depletion of SENP1 causes a reciprocal effect and reduces the transactivation properties of Elk-1. Partial redundancy of function with SENP2 is revealed by combinatorial knockdown studies. Importantly, depletion of SENP1 also reduces the activation of the Elk-1 target gene c-FOS. Taken together, these results therefore reveal an important role for SENP1 in the regulation of Elk-1-mediated gene expression in response to mitogenic signalling cues
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