Employee and partner surveys wave 3 of the Linked-Employer-Employee-Panel (LEEP-B3) Project (DFG – 373090005): Organizational Inequalities and Interdependencies between Capabilities in Work and Personal Life: A Study of Employees in Different Work Organizations. Technical Report

Marx C, Abendroth A, Bächmann A-C, et al. Employee and partner surveys wave 3 of the Linked-Employer-Employee-Panel (LEEP-B3) Project (DFG – 373090005): Organizational Inequalities and Interdependencies between Capabilities in Work and Personal Life: A Study of Employees in Different Work Organizations. Technical Report. Bielefeld: Univ., Fak. für Soziologie; 2020

The gravitational wave background from star-massive black hole fly-bys

Stars on eccentric orbits around a massive black hole (MBH) emit bursts of gravitational waves (GWs) at periapse. Such events may be directly resolvable in the Galactic centre. However, if the star does not spiral in, the emitted GWs are not resolvable for extra-galactic MBHs, but constitute a source of background noise. We estimate the power spectrum of this extreme mass ratio burst background (EMBB) and compare it to the anticipated instrumental noise of the Laser Interferometer Space Antenna (LISA). To this end, we model the regions close to a MBH, accounting for mass-segregation, and for processes that limit the presence of stars close to the MBH, such as GW inspiral and hydrodynamical collisions between stars. We find that the EMBB is dominated by GW bursts from stellar mass black holes, and the magnitude of the noise spectrum (f S_GW)^{1/2} is at least a factor ~10 smaller than the instrumental noise. As an additional result of our analysis, we show that LISA is unlikely to detect relativistic bursts in the Galactic centre.Comment: Accepted for publication by MNRAS; New appendix on population of phase space in presence of gravitational wave inspira

463 Vibostolimab plus pembrolizumab with/without docetaxel vs docetaxel in NSCLC after platinum chemotherapy and immunotherapy

BackgroundAgents blocking interactions between the T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) and its ligands (CD112, CD155) have demonstrated preclinical antitumor activity. Anti-TIGIT humanized monoclonal antibody vibostolimab (MK-7684) showed promising antitumor activity and manageable toxicity in heavily pretreated patients across multiple tumor types, particularly when combined with the PD-1 inhibitor pembrolizumab (NCT02964013). Pembrolizumab has significantly improved OS versus chemotherapy in PD-L1–positive advanced non–small-cell lung cancer (NSCLC). However, many patients present with primary or acquired resistance to immunotherapy. This phase 2 study (NCT04725188) evaluates efficacy and safety of MK-7684A, a co-formulation of vibostolimab plus pembrolizumab, administered with/without docetaxel versus docetaxel alone in patients with previously treated metastatic NSCLC.MethodsThis randomized, placebo- and active-controlled, multicenter, partial-blind study is enrolling adults with histologically/cytologically confirmed metastatic NSCLC with PD after platinum-doublet chemotherapy and 1 prior anti–PD-(L)1 therapy. Patients must have measurable disease per RECIST v1.1, ECOG PS of 0–1, and no known active CNS metastases (previously treated brain metastases allowed if radiologically/clinically stable). Tumor tissue from archival or newly-obtained core or excisional biopsies are evaluated centrally for PD-L1 expression before randomization, and local documentation of the absence of EGFR mutations or ALK/ROS1 gene rearrangements must be provided. Patients are randomized 1:1:1 to receive intravenous vibostolimab (200 mg) plus pembrolizumab (200 mg) Q3W (open-label), vibostolimab plus pembrolizumab plus docetaxel (standard-of-care dose) Q3W (blinded), or docetaxel plus placebo Q3W (blinded). Randomization is stratified by ECOG PS (0/1), prior anti–PD-(L)1 therapy (immediate/no immediate prior therapy), and PD-L1 tumor proportion score (<50%/≥50%). Treatment continues for up to 35 cycles (approximately 2 years) of vibostolimab plus pembrolizumab, and per locally approved label for docetaxel, or until PD, unacceptable AEs, intercurrent illness, or investigator decision. Patients with SD/PR/CR may be eligible for up to 17 additional rechallenge cycles of vibostolimab plus pembrolizumab following BICR-verified radiographic PD by RECIST v1.1 after initial treatment or first course is completed or stopped for confirmed CR. Primary endpoint is PFS per RECIST v1.1 by BICR. Secondary endpoints are OS, ORR and DOR per RECIST v1.1 by BICR, and safety. Radiographic imaging occurs at baseline, Q6W through week 36, Q9W through week 54, and then Q12W until PD, start of new anticancer treatment, withdrawal of consent, or death. AEs are assessed by NCI CTCAE v5.0. Approximately 240 patients will be randomized. Enrollment began in April of 2021, and is ongoing at 42 sites in 10 countries.AcknowledgementsMedical writing assistance was provided by Rozena Varghese, PharmD, CMPP, of ICON plc (North Wales, PA, USA), funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.Trial RegistrationClinicalTrials.gov, NCT04725188Ethics ApprovalAn independent institutional review board or ethics committee approved the protocol at each study site, and the trial is being conducted in compliance with Good Clinical Practice guidelines and the Declaration of Helsinki. All patients are required to provide informed consent prior to participation in the study

Type 2 Diabetes as a Risk Factor for Dementia in Women Compared With Men: A Pooled Analysis of 2.3 Million People Comprising More Than 100,000 Cases of Dementia

Objective: Type 2 diabetes confers a greater excess risk of cardiovascular disease in women than in men. Diabetes is also a risk factor for dementia, but whether the association is similar in women and men remains unknown. We performed a meta-analysis of unpublished data to estimate the sex-specific relationship between women and men with diabetes with incident dementia. Research design and methods: A systematic search identified studies published prior to November 2014 that had reported on the prospective association between diabetes and dementia. Study authors contributed unpublished sex-specific relative risks (RRs) and 95% CIs on the association between diabetes and all dementia and its subtypes. Sex-specific RRs and the women-to-men ratio of RRs (RRRs) were pooled using random-effects meta-analyses. Results: Study-level data from 14 studies, 2,310,330 individuals, and 102,174 dementia case patients were included. In multiple-adjusted analyses, diabetes was associated with a 60% increased risk of any dementia in both sexes (women: pooled RR 1.62 [95% CI 1.45-1.80]; men: pooled RR 1.58 [95% CI 1.38-1.81]). The diabetes-associated RRs for vascular dementia were 2.34 (95% CI 1.86-2.94) in women and 1.73 (95% CI 1.61-1.85) in men, and for nonvascular dementia, the RRs were 1.53 (95% CI 1.35-1.73) in women and 1.49 (95% CI 1.31-1.69) in men. Overall, women with diabetes had a 19% greater risk for the development of vascular dementia than men (multiple-adjusted RRR 1.19 [95% CI 1.08-1.30]; P \u3c 0.001). Conclusions: Individuals with type 2 diabetes are at ∼60% greater risk for the development of dementia compared with those without diabetes. For vascular dementia, but not for nonvascular dementia, the additional risk is greater in women

Salmonella Derby Clonal Spread from Pork

The genetic diversity of the Derby serotype of Salmonella enterica in Spain was examined by pulsed-field gel electrophoresis (PFGE). Out of 24 identified PFGE profiles, a major clone was detected in 19% of strains from humans, 52% from food, and 62% from swine. This clone (clone 1) was isolated from pork products, suggesting swine as its source

Osmolality and non-structural carbohydrate composition in the secondary phloem of trees across a latitudinal gradient in Europe

Phloem osmolality and its components are involved in basic cell metabolism, cell growth, and in various physiological processes including the ability of living cells to withstand drought and frost. Osmolality and sugar composition responses to environmental stresses have been extensively studied for leaves, but less for the secondary phloem of plant stems and branches. Leaf osmotic concentration and the share of pinitol and raffinose among soluble sugars increase with increasing drought or cold stress, and osmotic concentration is adjusted with osmoregulation. We hypothesize that similar responses occur in the secondary phloem of branches. We collected living bark samples from branches of adult Pinus sylvestris, Picea abies, Betula pendula and Populus tremula trees across Europe, from boreal Northern Finland to Mediterranean Portugal. In all studied species, the observed variation in phloem osmolality was mainly driven by variation in phloem water content, while tissue solute content was rather constant across regions. Osmoregulation, in which osmolality is controlled by variable tissue solute content, was stronger for Betula and Populus in comparison to the evergreen conifers. Osmolality was lowest in mid-latitude region, and from there increased by 37% toward northern Europe and 38% toward southern Europe due to low phloem water content in these regions. The ratio of raffinose to all soluble sugars was negligible at mid-latitudes and increased toward north and south, reflecting its role in cold and drought tolerance. For pinitol, another sugar known for contributing to stress tolerance, no such latitudinal pattern was observed. The proportion of sucrose was remarkably low and that of hexoses (i.e., glucose and fructose) high at mid-latitudes. The ratio of starch to all non-structural carbohydrates increased toward the northern latitudes in agreement with the build-up of osmotically inactive C reservoir that can be converted into soluble sugars during winter acclimation in these cold regions. Present results for the secondary phloem of trees suggest that adjustment with tissue water content plays an important role in osmolality dynamics. Furthermore, trees acclimated to dry and cold climate showed high phloem osmolality and raffinose proportion.Peer reviewe

Modelling collinear and spatially correlated data

In this work we present a statistical approach to distinguish and interpret the complex relationship between several predictors and a response variable at the small area level, in the presence of i) high correlation between the predictors and ii) spatial correlation for the response. Covariates which are highly correlated create collinearity problems when used in a standard multiple regression model. Many methods have been proposed in the literature to address this issue. A very common approach is to create an index which aggregates all the highly correlated variables of interest. For example, it is well known that there is a relationship between social deprivation measured through the Multiple Deprivation Index (IMD) and air pollution; this index is then used as a confounder in assessing the e ect of air pollution on health outcomes (e.g. respiratory hospital admissions or mortality). However it would be more informative to look specically at each domain of the IMD and at its relationship with air pollution to better understand its role as a confounder in the epidemiological analyses. In this paper we illustrate how the complex relationships between the domains of IMD and air pollution can be deconstructed and analysed using pro le regression, a Bayesian non-parametric model for clustering responses and covariates simultaneously. Moreover, we include an intrinsic spatial conditional autoregressive (ICAR) term to account for the spatial correlation of the response variable

Experimental assessment of inter-centre variation in stopping-power and range prediction in particle therapy

Purpose: Experimental assessment of inter-centre variation and absolute accuracy of stopping-power ratio (SPR) prediction within 17 particle therapy centres of the European Particle Therapy Network. Material and methods: A head and body phantom with seventeen tissue-equivalent materials were scanned consecutively at the participating centres using their individual clinical CT scan protocol and translated into SPR with their in-house CT-number-to-SPR conversion. Inter-centre variation and absolute accuracy in SPR prediction were quantified for three tissue groups: lung, soft tissues and bones. The integral effect on range prediction for typical clinical beams traversing different tissues was determined for representative beam paths for the treatment of primary brain tumours as well as lung and prostate cancer. Results: An inter-centre variation in SPR prediction (2 sigma) of 8.7%, 6.3% and 1.5% relative to water was determined for bone, lung and soft-tissue surrogates in the head setup, respectively. Slightly smaller variations were observed in the body phantom (6.2%, 3.1%, 1.3%). This translated into inter-centre variation of integral range prediction (2 sigma) of 2.9%, 2.6% and 1.3% for typical beam paths of prostate-, lung-and primary brain-tumour treatments, respectively. The absolute error in range exceeded 2% in every fourth participating centre. The consideration of beam hardening and the execution of an independent HLUT validation had a positive effect, on average. Conclusion: The large inter-centre variations in SPR and range prediction justify the currently clinically used margins accounting for range uncertainty, which are of the same magnitude as the inter-centre variation. This study underlines the necessity of higher standardisation in CT-number-to-SPR conversion. (C) 2021 The Authors. Published by Elsevier B.V