Ermüdungssicherheit von Brücken – Teil 2: Nachweis basierend auf den Messwerten des Monitoring-Projekts „Bahnbrücke Eglisau“

Bei der genieteten Rheinbrücke in Eglisau wurde über einen Zeitraum von einem Jahr ein Monitoring durchgeführt. Die mittels Rainflow-Analyse ausgewerteten Messwerte dienten als Grundlage für den Nachweis der Ermüdungssicherheit. Die Messquerschnitte sind in der Regel nicht identisch mit den Nachweisquerschnitten, weshalb die gemessenen Dehnungen bzw. Spannungen in die für den Nachweis maßgebende Nietlage des Nachweisquerschnittes umgerechnet wurden. Die hierfür erforderlichen Umrechnungsfaktoren wurden rechnerisch am statischen Modell ermittelt. In einem ersten Schritt wurde die Dauerfestigkeit für die ermüdungsbeanspruchten Bauteile untersucht. Für die Bauteile mit ungenügender Dauerfestigkeit wurde anschließend eine Schadensakkumulationsberechnung nach Palmgren-Miner auf Basis der für genietete Konstruktionsdetails geltenden Wöhlerkurven durchgeführt. Basierend auf den Messwerten aus dem Monitoring konnte schließlich für die Nietkonstruktion eine genügende Ermüdungssicherheit und für das maßgebende Bauteil eine weitere Nutzungsdauer von mindestens 50 Jahren nachgewiesen werden. Fatigue safety of riveted bridges – Part 2: Verification based on the monitoring data of the project “Railway Bridge at Eglisau“. Long term monitoring over one year has been conducted on the riveted Railway Bridge over the Rhine at Eglisau. Measured values were exploited by rainflow analysis and served as the basis for the verification of fatigue safety. As the locations of measurements are generally not identical with the cross sections of verification, measured strains respectively stresses, were extrapolated to the relevant verification cross section by means of factors that were obtained by structural analysis. Using these values, all fatigue relevant structural details were first verified with respect to the fatigue limit. Then, damage accumulation calculation according to the Palmgren-Miner rule and based on Wöhler curves for riveted details was performed for those structural details where the fatigue limit check was not fulfilled. Sufficient fatigue safety could finally be verified for the whole riveted structure and an additional service life of at least 50 years for the most fatigue relevant structural element

CART cells are prone to Fas- and DR5-mediated cell death.

Adoptive transfer of T cells transduced with Chimeric Antigen Receptors (CAR) are now FDA-approved for the treatment of B-cell malignancies. Yet, the functionality of the endogenous TCR in CART cells has not been fully assessed. Here, we demonstrate that CART cells progressively upregulate Fas, FasL, DR5 and TRAIL, which result in their programmed cell death, independently of antigen-mediated TCR or CAR activation. CART cell apoptosis occurs even when the CAR contains a single (co-)activatory domain such as CD3ζ, CD28 or 4-1BB. Importantly, the dominant role of the Fas and DR5 pathways in CART cell apoptosis is demonstrated by the significant rescue of CART cells upon in vivo blockade by combined Fas-Fc and DR5-Fc recombinant proteins. These observations are of crucial importance for the long-term persistence of CART cells and for the development of new applications including the combined TCR and CAR activation against solid tumors

Effectiveness of a peer educator-coordinated preference-based differentiated service delivery model on viral suppression among young people living with HIV in Lesotho: the PEBRA cluster-randomized trial

BACKGROUND: Southern and Eastern Africa is home to more than 2.1 million young people aged 15 to 24 years living with HIV. As compared with other age groups, this population group has poorer outcomes along the HIV care cascade. Young people living with HIV and the research team co-created the PEBRA (Peer Educator-Based Refill of ART) care model. In PEBRA, a peer educator (PE) delivered services as per regularly assessed patient preferences for medication pick-up, short message service (SMS) notifications, and psychosocial support. The cluster-randomized trial compared PEBRA model versus standard clinic care (no PE and ART refill done by nurses) in 3 districts in Lesotho. METHODS AND FINDINGS: Individuals taking antiretroviral therapy (ART) aged 15 to 24 years at 20 clinics (clusters) were eligible. In the 10 clinics randomized to the intervention arm, participants were offered the PEBRA model, coordinated by a trained PE and supported by an eHealth application (PEBRApp). In the 10 control clusters, participants received standard nurse-coordinated care without any service coordination by a PE. The primary endpoint was 12-month viral suppression below 20 copies/mL. Analyses were intention-to-treat and adjusted for sex. From November 6, 2019 to February 4, 2020, we enrolled 307 individuals (150 intervention, 157 control; 218 [71%] female, median age 19 years [interquartile range, IQR, 17 to 22]). At 12 months, 99 of 150 (66%) participants in the intervention versus 95 of 157 (61%) participants in the control arm had viral suppression (adjusted odds ratio (OR) 1.27; 95% confidence interval [CI] [0.79 to 2.03]; p = 0.327); 4 of 150 (2.7%) versus 1 of 157 (0.6%) had died (adjusted OR 4.12; 95% CI [0.45 to 37.62]; p = 0.210); and 12 of 150 (8%) versus 23 of 157 (14.7%) had transferred out (adjusted OR 0.53; 95% CI [0.25 to 1.13]; p = 0.099). There were no significant differences between arms in other secondary outcomes. Twenty participants (11 in intervention and 9 in control) were lost to follow-up over the entire study period. The main limitation was that the data collectors in the control clusters were also young peers; however, they used a restricted version of the PEBRApp to collect data and thus were not able to provide the PEBRA model. The trial was prospectively registered on ClinicalTrials.gov (NCT03969030). CONCLUSIONS: Preference-based peer-coordinated care for young people living with HIV, compared to nurse-based care only, did not lead to conclusive evidence for an effect on viral suppression. TRIAL REGISTRATION: clinicaltrials.gov, NCT03969030, https://clinicaltrials.gov/ct2/show/NCT03969030

Joint field experiments for comparisons of measuring methods of photosynthetic production

During the 1st GAP Workshop at Konstanz in April 1982 comparative measurements of phytoplankton primary production by several techniques were conducted simultaneously at an offshore station in Lake Konstanz and an experimental algal pond. Suspended glass bottle exposure techniques using 14C and 13C uptake gave Pz (mg C m−3 h−1) values which varied considerably near-surface, but estimates of areal rates for the euphotic zone ΣPcu(mg C m−3 h−1) which were reasonably close. In the lake, ΣPz, from a vertical tube exposure (with 14C uptake) was greater than rates derived for integrated bottle samples. The oxygen bottle method permitted a good estimate of compensation depth, corresponding to in situ growth studies. There were difficulties in direct comparison between O2 and carbon methods. Correlation between them for Pz was good in the lake but poor in the pond, both for suspended bottle and vertical tube methods. This series demonstrates that despite reasonable overall estimates, comparatively minor methodological differences in experimental technique can cause large variatio

Emergence of human immunodeficiency virus-1 drug resistance during the 3-month World Health Organization-recommended enhanced adherence counseling period in the CART-1 cohort study

Background: In resource-limited settings, the World Health Organization recommends enhanced adherence counseling (EAC) for individuals with an unsuppressed human immunodeficiency virus (HIV)-1 viral load (VL) and to remeasure VL after 3 months to avoid unnecessary regimen switches. In cases in which this follow-up VL remains unsuppressed, a regimen switch is indicated. We aimed to assess levels of HIV-1 drug resistance before and after the EAC period among people with ongoing viremia (>/=80 c/mL) after EAC. Methods: We included adult participants of the CART-1 cohort study conducted in Lesotho who had a VL >/=80 c/mL after EAC. Paired plasma samples (before and after EAC) were analyzed by next-generation sequencing. We assessed the prevalence of resistance-associated mutations and viral susceptibility scores to each participant's antiretroviral therapy (ART) regimen (range, 0-3; 3 indicates complete susceptibility). Results: Among 93 participants taking nonnucleoside reverse-transcriptase inhibitor-based ART with an initial VL >/=1000 copies/mL who received a follow-up VL test after EAC, 76 still had a VL >/=80 copies/mL after EAC, and paired samples were available for 57 of 76. The number of individuals without full susceptibility to any drug in their regimen increased from 31 of 57 (54.4%) before to 36 of 57 (63.2%) after EAC. Median susceptibility scores dropped from 0.5 (interquartile range [IQR] = 0.25-) to 0.25 (IQR = 0.25-1) during the EAC period (P = .16). Conclusions: Despite high levels of resistance before EAC, we observed a slight decline in susceptibility scores after EAC. The risk of further accumulation of resistance during EAC has to be balanced against the benefit of avoiding unnecessary switches in those with spontaneous resuppression after EAC

Assessment of a viral load result-triggered automated differentiated service delivery model for people taking ART in Lesotho (the VITAL study): study protocol of a cluster-randomized trial

INTRODUCTION: To sustainably provide good quality care to increasing numbers of people living with HIV (PLHIV) receiving antiretroviral therapy (ART) in resource-limited settings, care delivery must shift from a "one-size-fits-all" approach to differentiated service delivery models. Such models should reallocate resources from PLHIV who are doing well to groups of PLHIV who may need more attention, such as those with treatment failure. The VIral load Triggered ART care Lesotho (VITAL) trial assesses a viral load (VL)-, participant's preference-informed, electronic health (eHealth)-supported, automated differentiated service delivery model (VITAL model). With VITAL, we aim to assess if the VITAL model is at least non-inferior to the standard of care in the proportion of participants engaged in care with viral suppression at 24 months follow-up and if it is cost-saving. METHODS: The VITAL trial is a pragmatic, multicenter, cluster-randomized, non-blinded, non-inferiority trial with 1:1 allocation conducted at 18 nurse-led, rural health facilities in two districts of northern Lesotho, enrolling adult PLHIV taking ART. In intervention clinics, providers are trained to implement the VITAL model and are guided by a clinical decision support tool, the VITALapp. VITAL differentiates care according to VL results, clinical characteristics, sub-population and participants' and health care providers' preferences. EXPECTED OUTCOMES: Evidence on the effect of differentiated service delivery for PLHIV on treatment outcomes is still limited. This pragmatic cluster-randomized trial will assess if the VITAL model is at least non-inferior to the standard of care and if it is cost saving. TRIAL REGISTRATION: The study has been registered with clinicaltrials.gov (Registration number NCT04527874; August 27, 2020)

The living and the dead; an investigation into the status of erasure within the floor of Bath Abbey

The floor of Bath Abbey offers a singular test of authenticity. Nineteenth century repairs and additions caused horizontal grave markers, which comprise the majority of the Abbey’s floor, to become separated from the burial sites they were intended to memorialize. A century and a half of further occupation has had the effect of removing many inscriptions as surfaces are worn smooth. The result is a patchwork of unintended edits and accidental poetry. This paper explores the notions of authenticity, essence, memorial and erasure as they pertain to the Abbey floor, in particular with regard to the role the body plays in inhabiting/eroding the floor—from both above and below. The author argues that the stones which are most out of place or worn to a state of erasure are no less authentic than their intact equivalents, but that they can be considered to have moved to another state of authenticity rich in resonance and meaning. This paper, in short, is a defense of erasure and that erosion through occupation may be considered a form of social memory; indeed, the marks of walking become the inscription. In other words, the undesigned (erasure, the cutting and repositioning of ledger stones, the missing inscriptions) becomes considered not as a form of dirt but as the positive traces of on-going and meaningful occupation

Similar but different: Integrated phylogenetic analysis of Austrian and Swiss HIV-1 sequences reveal differences in transmission patterns of the local HIV-1 epidemics.

OBJECTIVES Phylogenetic analyses of two or more countries allow to detect differences in transmission dynamics of local HIV-1 epidemics beyond differences in demographic characteristics. METHODS A maximum-likelihood phylogenetic tree was built using pol-sequences of the Swiss HIV Cohort Study (SHCS) and the Austrian HIV Cohort Study (AHIVCOS), with international background sequences. Three types of phylogenetic cherries (clusters of size 2) were analyzed further: 1) Domestic cherries, 2) International cherries and 3) SHCS/AHIVCOS-cherries. Transmission group and ethnicities observed within the cherries were compared to the respective distribution expected from a random distribution of patients on the phylogeny. RESULTS The demographic characteristics of the AHIVCOS (included patients: 3'141) and the SHCS (included patients: 12'902) are very similar. In the AHIVCOS, 36.5% of the patients were in domestic cherries, 8.3% in international cherries, and 7.0% in SHCS/AHIVCOS cherries. Similarly, in the SHCS, 43.0% of the patients were in domestic cherries, 8.2% in international cherries, and 1.7% in SHCS/AHIVCOS cherries. While international cherries in the SHCS were dominated by heterosexuals (HET) with MSM being underrepresented, the opposite was the case for the AHIVCOS. In both cohorts, cherries with one patient belonging to the transmission group intravenous drug user (IDU) and the other one non-IDU were underrepresented. CONCLUSION In both cohorts, international HIV transmission plays a major role in the local epidemics, mostly driven by MSM in the AHIVOS, and by HET in the SHCS, highlighting the importance of international collaborations to understand global HIV transmission links on the way to eliminate HIV

Correction to: CART cells are prone to Fas- and DR5-mediated cell death.

After publication of this article [1], it was noticed that 3 authors were missed from the author list