High torque tenovirus (TTV) load before first vaccine dose is associated with poor serological response to COVID-19 vaccination in lung transplant recipients

BACKGROUND: : Serological responses to COVID-19 vaccination are diminished in recipients of solid organ transplants, especially in lung transplant recipients (LTR), probably as result of immunosuppressive treatment. There is currently no marker of immunosuppression that can be used to predict the COVID-19 vaccination response. Here, we study whether torque tenovirus (TTV), a highly prevalent virus can be used as an indicator of immunosuppression. METHODS: : The humoral response to the mRNA 1273 vaccine was assessed in 103 LTR, who received a transplant between 4 and 237 months prior to vaccination, by measuring Spike (S)-specific IgG levels at baseline, 28 days after first, and 28 days after the second vaccination. TTV loads were determined by RT-PCR and Pearson's correlation coefficient was calculated to correlate serological responses to TTV load. RESULTS: : Humoral responses to COVID-19 vaccination were observed in 41/103 (40%) LTR at 28 days after the second vaccination. 62/103 (60%) were non-responders. Lower TTV loads at baseline (significantly) correlated with higher S-specific antibodies and a higher percentage of responders. Lower TTV loads also strongly correlated with longer time since transplantation, indicating that participants with lower TTV loads were longer after transplantation. CONCLUSIONS: : This study shows a better humoral response to the SARS-CoV-2 vaccine in subjects with a lower TTV load pre-vaccination. In addition, TTV load correlates with the time after transplantation. Further studies on the use of TTV load in vaccination efficacy studies in immunocompromised cohorts should provide leads for the potential use of this marker for optimizing vaccination response

mRNA-1273 COVID-19 vaccination in patients receiving chemotherapy, immunotherapy, or chemoimmunotherapy for solid tumours:a prospective, multicentre, non-inferiority trial

BACKGROUND: Patients with cancer have an increased risk of complications from SARS-CoV-2 infection. Vaccination to prevent COVID-19 is recommended, but data on the immunogenicity and safety of COVID-19 vaccines for patients with solid tumours receiving systemic cancer treatment are scarce. Therefore, we aimed to assess the impact of immunotherapy, chemotherapy, and chemoimmunotherapy on the immunogenicity and safety of the mRNA-1273 (Moderna Biotech, Madrid, Spain) COVID-19 vaccine as part of the Vaccination Against COVID in Cancer (VOICE) trial. METHODS: This prospective, multicentre, non-inferiority trial was done across three centres in the Netherlands. Individuals aged 18 years or older with a life expectancy of more than 12 months were enrolled into four cohorts: individuals without cancer (cohort A [control cohort]), and patients with solid tumours, regardless of stage and histology, treated with immunotherapy (cohort B), chemotherapy (cohort C), or chemoimmunotherapy (cohort D). Participants received two mRNA-1273 vaccinations of 100 μg in 0·5 mL intramuscularly, 28 days apart. The primary endpoint, analysed per protocol (excluding patients with a positive baseline sample [>10 binding antibody units (BAU)/mL], indicating previous SARS-CoV-2 infection), was defined as the SARS-CoV-2 spike S1-specific IgG serum antibody response (ie, SARS-CoV-2-binding antibody concentration of >10 BAU/mL) 28 days after the second vaccination. For the primary endpoint analysis, a non-inferiority design with a margin of 10% was used. We also assessed adverse events in all patients who received at least one vaccination, and recorded solicited adverse events in participants who received at least one vaccination but excluding those who already had seroconversion (>10 BAU/mL) at baseline. This study is ongoing and is registered with ClinicalTrials.gov, NCT04715438. FINDINGS: Between Feb 17 and March 12, 2021, 791 participants were enrolled and followed up for a median of 122 days (IQR 118 to 128). A SARS-CoV-2-binding antibody response was found in 240 (100%; 95% CI 98 to 100) of 240 evaluable participants in cohort A, 130 (99%; 96 to >99) of 131 evaluable patients in cohort B, 223 (97%; 94 to 99) of 229 evaluable patients in cohort C, and 143 (100%; 97 to 100) of 143 evaluable patients in cohort D. The SARS-CoV-2-binding antibody response in each patient cohort was non-inferior compared with cohort A. No new safety signals were observed. Grade 3 or worse serious adverse events occurred in no participants in cohort A, three (2%) of 137 patients in cohort B, six (2%) of 244 patients in cohort C, and one (1%) of 163 patients in cohort D, with four events (two of fever, and one each of diarrhoea and febrile neutropenia) potentially related to the vaccination. There were no vaccine-related deaths. INTERPRETATION: Most patients with cancer develop, while receiving chemotherapy, immunotherapy, or both for a solid tumour, an adequate antibody response to vaccination with the mRNA-1273 COVID-19 vaccine. The vaccine is also safe in these patients. The minority of patients with an inadequate response after two vaccinations might benefit from a third vaccination. FUNDING: ZonMw, The Netherlands Organisation for Health Research and Development

De geprotocolleerde Interapy-behandeling van depressie via het internet; resultaten van een gerandomiseerde trial

Psychologische behandelingen via internet bieden een nieuwe mogelijkheid voor de geestelijke gezondheidszorg. In samenwerking met de Stichting Mentrum ggz Amsterdam heeft Interapy een behandeling voor depressie via internet opgezet. De behandeling bestaat uit cognitief-gedragstherapeutische interventies, zoals psycho-educatie, schrijfopdrachten, registratie, activatie, het uitdagen van negatieve automatische gedachten en terugvalpreventie. Dit artikel beschrijft de procedure, de behandeling en de resultaten van een vergelijkende studie onder cliënten die matig tot ernstig depressief waren. De cliënten die direct actief werden behandeld (N = 32) verbeterden significant meer dan de cliënten in de psycho-educatieconditie (N = 14). Deze tweede groep kreeg de actieve behandeling ongeveer twaalf weken later. De effecten waren groot. In de actief behandelde groep liet 75 procent van de cliënten klinisch relevante verbetering zien, in de psycho-educatieconditie was dat percentage 36. Uit de follow-up na zes weken bleek dat de verbeteringen standhielden

Environmental movements in space-time: the Czech and Slovak republics from Stalinism to post-socialism

To demonstrate the role of space and time in social movements, the paper analyses the evolution and context of the environmental movement in the Czech and Slovak republics from 1948 to 1998. It shows that the movement's identity was formed under socialism and that political opportunity and resource availability changed markedly over time, as did its organisational and spatial structure. The movement played a significant part in the collapse of the socialist regime, but in the 1990s was marginalised in the interests of building a market economy and an independent Slovakia. Nevertheless a diverse and flexible range of groups existed by the late 1990s. The successive space-times allow analysis of the multiple and changing variables that influence the geography of social movements

Near-Infrared interferometry of Eta Carinae with high spatial and spectral resolution using the VLTI and the AMBER instrument

We present the first NIR spectro-interferometry of the LBV Eta Carinae. The K band observations were performed with the AMBER instrument of the ESO Very Large Telescope Interferometer using three 8.2m Unit Telescopes with baselines from 42 to 89m. The aim of this work is to study the wavelength dependence of Eta Car's optically thick wind region with a high spatial resolution of 5 mas (11 AU) and high spectral resolution. The medium spectral resolution observations (R=1,500) were performed in the wavelength range around both the HeI 2.059 micron and the Br gamma 2.166 micron emission lines, the high spectral resolution observations (R=12,000) only in the Br gamma line region. In the K-band continuum, a diameter of 4.0 +/-0.2 mas (Gaussian FWHM, fit range 28-89m) was measured for Eta Car's optically thick wind region. If we fit Hillier et al. (2001) model visibilities to the observed AMBER visibilities, we obtain 50 % encircled-energy diameters of 4.2, 6.5 and 9.6mas in the 2.17 micron continuum, the HeI, and the Br gamma emission lines, respectively. In the continuum near the Br gamma line, an elongation along a position angle of 120+/-15 degrees was found, consistent with previous VLTI/VINCI measurements by van Boekel et al. (2003). We compare the measured visibilities with predictions of the radiative transfer model of Hillier et al. (2001), finding good agreement. Furthermore, we discuss the detectability of the hypothetical hot binary companion. For the interpretation of the non-zero differential and closure phases measured within the Br gamma line, we present a simple geometric model of an inclined, latitude-dependent wind zone. Our observations support theoretical models of anisotropic winds from fast-rotating, luminous hot stars with enhanced high-velocity mass loss near the polar regions.Comment: 22 pages, 14 figures, 2 tables; A&A in pres

Persistent Cellular Motion Control and Trapping Using Mechanotactic Signaling

Chemotactic signaling and the associated directed cell migration have been extensively studied owing to their importance in emergent processes of cellular aggregation. In contrast, mechanotactic signaling has been relatively overlooked despite its potential for unique ways to artificially signal cells with the aim to effectively gain control over their motile behavior. The possibility of mimicking cellular mechanotactic signals offers a fascinating novel strategy to achieve targeted cell delivery for in vitro tissue growth if proven to be effective with mammalian cells. Using (i) optimal level of extracellular calcium ([Ca2[superscript +] ][subscript ext] = 3 mM) we found, (ii) controllable fluid shear stress of low magnitude (σ < 0.5 Pa), and (iii) the ability to swiftly reverse flow direction (within one second), we are able to successfully signal Dictyostelium discoideum amoebae and trigger migratory responses with heretofore unreported control and precision. Specifically, we are able to systematically determine the mechanical input signal required to achieve any predetermined sequences of steps including straightforward motion, reversal and trapping. The mechanotactic cellular trapping is achieved for the first time and is associated with a stalling frequency of 0.06 ~ 0.1 Hz for a reversing direction mechanostimulus, above which the cells are effectively trapped while maintaining a high level of directional sensing. The value of this frequency is very close to the stalling frequency recently reported for chemotactic cell trapping [Meier B, et al. (2011) Proc Natl Acad Sci USA 108:11417–11422], suggesting that the limiting factor may be the slowness of the internal chemically-based motility apparatus.SUTD-MIT International Design Centre (Grant IDG31400104

The CHIP-Family study to improve the psychosocial wellbeing of young children with congenital heart disease and their families: design of a randomized controlled trial

Background: Children with congenital heart disease (CHD) are at increased risk for behavioral, emotional, and cognitive problems. They often have reduced exercise capacity and participate less in sports, which is associated with a lower quality of life. Starting school may present more challenges for children with CHD and their families than for families with healthy children. Moreover, parents of children with CHD are at risk for psychosocial problems. Therefore, a family-centered psychosocial intervention for children with CHD when starting school is needed. Until now, the 'Congenital Heart Disease Intervention Program (CHIP) - School' is the only evidence-based intervention in this field. However, CHIP-School targeted parents only and resulted in non-significant, though positive, effects as to child psychosocial wellbeing. Hence, we expanded CHIP by adding a specific child module and including siblings, creating the CHIP-Family intervention. The CHIP-Family study aims to (1) test the effects of CHIP-Family on parental mental health and psychosocial wellbeing of CHD-children and to (2) identify baseline psychosocial and medical predictors for the e

European all-cause excess and influenza-attributable mortality in the 2017/18 season: should the burden of influenza B be reconsidered?

Objectives Weekly monitoring of European all-cause excess mortality, the EuroMOMO network, observed high excess mortality during the influenza B/Yamagata dominated 2017/18 winter season, especially among elderly. We describe all-cause excess and influenza-attributable mortality during the season 2017/18 in Europe. Methods Based on weekly reporting of mortality from 24 European countries or sub-national regions, representing 60% of the European population excluding the Russian and Turkish parts of Europe, we estimated age stratified all-cause excess morality using the EuroMOMO model. In addition, age stratified all-cause influenza-attributable mortality was estimated using the FluMOMO algorithm, incorporating influenza activity based on clinical and virological surveillance data, and adjusting for extreme temperatures. Results Excess mortality was mainly attributable to influenza activity from December 2017 to April 2018, but also due to exceptionally low temperatures in February-March 2018. The pattern and extent of mortality excess was similar to the previous A(H3N2) dominated seasons, 2014/15 and 2016/17. The 2017/18 overall all-cause influenza-attributable mortality was estimated to be 25.4 (95%CI 25.0-25.8) per 100,000 population; 118.2 (116.4-119.9) for persons aged 65. Extending to the European population this translates into over-all 152,000 deaths. Conclusions The high mortality among elderly was unexpected in an influenza B dominated season, which commonly are considered to cause mild illness, mainly among children. Even though A(H3N2) also circulated in the 2017/18 season and may have contributed to the excess mortality among the elderly, the common perception of influenza B only having a modest impact on excess mortality in the older population may need to be reconsidered.Peer Reviewe