Impact of regulatory safety notices on valproate prescribing and pregnancy outcome among women of child-bearing potential in Scotland: a population-based cohort study

Objective: To examine the impact of Medicines and Healthcare products Regulatory Agency (MHRA) safety alerts on valproate prescribing among women aged 14–45 years in Scotland and examine trends in pregnancies exposed to valproate. Design: Population-based cohort study. Participants: 21 983 women of all ages who received valproate between January 2011 and December 2019. Methods: All valproate prescriptions issued to women in Scotland between January 2011 and December 2019 were identified and prevalence/incidence rates per 10 000 population derived. The impact of regulatory safety alerts on prescribing was analysed using Joinpoint models. Linked pregnancy records for January 2011 to September 2019 were identified and annual rates of pregnancy per 1000 valproate-treated women aged 14–45 years were calculated for each pregnancy outcome: live birth, stillbirth, miscarriage and termination. Results: Annual prevalent and incident rates of valproate prescribing declined in women aged 14–45 years between 2011 and 2019 from 40.5 to 18.3 per 10 000 population (54.8% reduction) and 7.9 to 1.3 per 10 000 population (83.5% reduction), respectively. Statistically significant changes occurred around the times of the MHRA safety alerts. The number of valproate-exposed pregnancies conceived each year fell from 70 in 2011 to 20 in 2018, a 71.4% reduction, and the number of live births fell from 52 to 14, a 73.0% reduction. Expressed as a rate this was a 46.4% decrease from 15.3 to 8.2 per 1000 valproate-treated women aged 14–45 years in 2011 and 2018, respectively. Live birth was the most common pregnancy outcome. Conclusion: This study demonstrates, for the first time, the capabilities of national data sets to identify drug exposure and derive pregnancy outcome at scale across Scotland. Building on this as part of an evolving national/UK surveillance capability will continue efforts to minimise in-utero exposure to valproate; enabling ongoing surveillance to understand better long-term outcomes, and to inform better provision of health and wider support services

Experiences and Perceptions of the Supervisory Relationship in BIPOC Health Service Psychology Dyads

https://commons.und.edu/cehd-conference/1003/thumbnail.jp

Location of upper borders of cavities containing dust and gas under pressure in comets

The distance between the pre-impact surface of Comet 9P/Tempel 1 and the upper border of the largest cavity excavated during ejection of material after the collision of the impact module of the Deep Impact spacecraft with the comet is estimated to be about 5-6 metres if the diameter of the DI transient crater was about 150-200 m. The estimated distance was 4 m at the diameter was 100 m. This result suggests that cavities containing dust and gas under pressure located a few metres below surfaces of comets can be frequent.Comment: Monthly Notices of Royal Astronomical Society, 2012, in press, 7 page

Effect of hydrostatic pressure on degradation of CdTe/CdMgTe heterostructures grown by molecular beam epitaxy on GaAs substrates

We have shown that external hydrostatic pressure leads to the creation of structural defects, mainly in the vicinity of the II-VI/GaAs interface in the CdTe/Cd{sub 1-x}Mg{sub x}Te heterostructures grown by the molecular beam epitaxy method on GaAs substrates. These defects propagating across the epilayer cause permanent damage to the samples from the point of view of their electrical properties. In contrast, photoluminescence spectra are only weakly influenced by pressure. Our results shed light on the degradation process observed even without pressure in II-VI-based heterostructures

Outburst activity in comets: II. A multi-band photometric monitoring of comet 29p/Schwassmann-Wachmann 1

We have carried out a continuous multi-band photometric monitoring of the nuclear activity of comet 29P/Schwassmann-Wachmann 1 from 2008 to 2010. Our main aim has been to study the outburst mechanism on the basis of a follow-up of the photometric variations associated with the release of dust. We used a standardized method to obtain the 10 arc-sec nucleus photometry in the V, R, and I filters of the Johnson-Kron-Cousins system, being accurately calibrated with standard Landolt stars. Production of dust in the R and I bands during the 2010 Feb. 3 outburst has been also computed. We conclude that the massive ejection of large (optically-thin) particles from the surface at the time of the outburst is the triggering mechanism to produce the outburst. Ulterior sublimation of these ice-rich dust particles during the following days induces fragmentation, generating micrometer-sized grains that increase the dust spatial density to produce the outburst in the optical range due to scattering of sun light. The material leaving the nucleus adopts a fan-like dust feature, formed by micrometer-sized particles that are decaying in brightness as it evolved outwards. By analyzing the photometric signal measured in a standardized 10-arcsec aperture using the Phase Dispersion Minimization technique we have found a clear periodicity of 50 days. Remarkably, this value is also consistent with an outburst frequency of 7.4 outbursts/year deduced from the number of outbursts noticed during the effective observing time.Comment: 19 pages, 3 Tables, and 6 figure

Anti-SARS-CoV-2 antibody-containing plasma improves outcome in patients with hematologic or solid cancer and severe COVID-19: a randomized clinical trial

Patients with cancer are at high risk of severe coronavirus disease 2019 (COVID-19), with high morbidity and mortality. Furthermore, impaired humoral response renders severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines less effective and treatment options are scarce. Randomized trials using convalescent plasma are missing for high-risk patients. Here, we performed a randomized, open-label, multicenter trial (https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001632-10/DE) in hospitalized patients with severe COVID-19 (n = 134) within four risk groups ((1) cancer (n = 56); (2) immunosuppression (n = 16); (3) laboratory-based risk factors (n = 36); and (4) advanced age (n = 26)) randomized to standard of care (control arm) or standard of care plus convalescent/vaccinated anti-SARS-CoV-2 plasma (plasma arm). No serious adverse events were observed related to the plasma treatment. Clinical improvement as the primary outcome was assessed using a seven-point ordinal scale. Secondary outcomes were time to discharge and overall survival. For the four groups combined, those receiving plasma did not improve clinically compared with those in the control arm (hazard ratio (HR) = 1.29; P = 0.205). However, patients with cancer experienced a shortened median time to improvement (HR = 2.50; P = 0.003) and superior survival with plasma treatment versus the control arm (HR = 0.28; P = 0.042). Neutralizing antibody activity increased in the plasma cohort but not in the control cohort of patients with cancer (P = 0.001). Taken together, convalescent/vaccinated plasma may improve COVID-19 outcomes in patients with cancer who are unable to intrinsically generate an adequate immune response

Community as the Church of Tomorrow. Ecclesial "Communio" in Christ in terms of Franciszek Blachnicki

Boskie pochodzenie Kościoła i implikacja dzieła Trzech Osób Boskich wyraża lud zjednoczony w jedności Ojca i Syna i Ducha Świętego. W nim człowiek zanurzony doświadcza pośrednictwa zbawczego w komunikacji z Chrystusem Zmartwychwstałym. Zbawcza komunikacja to dar i uczestnictwo w Boskim życiu, przez i w pośrednictwie Kościoła. Swoje głębokie zakorzenienie w eklezjologii communio doskonale widział Sługa Boży ks. Franciszek Blachnicki. Oryginalność jego spojrzenia polega na tym, iż doskonale odczytał myśl eklezjalną Soboru Watykańskiego II. Dążył także do zaimplementowania tejże wizji w autentycznym przekazie wiary w Kościele. Blachnicki widział Kościół, który jest wspólnotową drogą człowieka ku zbawieniu wypełnionym w Jezusie Chrystusie. Na tym tle niezaprzeczalnie można dzisiaj uznać tę myśl za iście prorocką w kontekście nowej ewangelizacji.The Divine origin of the Church and the implication of the works of the Holy Trinity is expressed by the people united in the unity of the Father and of the Son and of the Holy Spirit. This means people integrated into the unique community called communio. It is the relationship of man with the Triune, Personal Creator, Redeemer and Savior of the human race in the “interdependence”, which we call – the Church. This community, began in the consciousness of faith, seeks to reach the eschatic fulfillment. One immersed in it experiences the salvific mediation in communication with the Risen Christ. The saving communication is a gift and participation in the divine life, “through” and “in” the mediation of the Church. Father Franciszek Blachnicki, the Servant of God, has seen his own deepest roots in the ecclesiology of communion. The originality of his approach is based on a splendid interpretation of ecclesial reflection on Church which was done by The Second Vatican Council. Blachnicki has also sought to implement this vision in the authentic transmission of the faith in the Church. He has seen the Church as the Community way of the man towards salvation fulfilled in Jesus Christ. In today’s context of the new evangelization this reflection can be undeniably considered as an idea of a truly prophetic kind

Structural and functional characteristics of aldo-keto reductase from the pathogenic bacteria strain

Celem pracy było scharakteryzowanie struktury oraz funkcji białka IDP93879, aldo-keto reduktazy pochodzenia bakteryjnego z patogennego szczepu Yersinia enterocolitica. Zoptymalizowano warunki hodowli oraz ekspresji wykorzystując szczepy E. coli BL21-CodonPlus (DE3)-RIL oraz ArcticExpress (DE3). Jako wektor wykorzystano plazmid pMCSG-7, który wprowadza znacznik histydynowy (6xHIS) ułatwiający jego detekcję i oczyszczanie. Stabilne aktywne białko oczyszczono ze szczepu ArcticExpress w warunkach niskich temperatur za pomocą chromatografii powinowactwa z użyciem złoża niklowego. Wykonano badania aktywności enzymu sporządzając bazę potencjalnych substratów i wykonując spektrofotometryczne pomiary kinetyczne. Wyłoniono dwa potencjalne substraty: 2-nitrobenzaldehyd oraz 2,6-dichlorobenzaldehyd. Wykonano próbę krystalizacji białka z metką histydynową oraz po jej odtrawieniu. Nie udało się uzyskać kryształów białka.The aim of the project was to characterize the structure and function of protein IDP93879, an aldo-keto reductase of bacterial origin from the pathogenic Yersinia enterocolitica strain. Expression conditions were optimized using E. coli BL21-CodonPlus (DE3) -RIL and ArcticExpress (DE3) strains. The expression vector was pMCSG-7, which introduces a histidine tag (6xHIS) to the expressed protein to facilitate its detection and purification. The stable active protein was purified from the ArcticExpress strain under low-temperature conditions by nickel affinity chromatography. Enzyme activity tests were performed by making a potential substrates library and performing spectrophotometric kinetic measurements. Two potential substrates were found: 2-nitrobenzaldehyde and 2,6-dichlorobenzaldehyde. An attempt was made to crystallize the protein with the histidine tag and after it was digested. Protein crystals have been not obtained