The Biological Standard of Living in the two Germanies.

Physical stature is used as a proxy for the biological standard of living in the two Germanies before and after unification in an analysis of a cross-sectional sample (1998) of adult heights, as well as among military recruits of the 1990s. West Germans tended to be taller than East Germans throughout the period under consideration. Contrary to official proclamations of a classless society, there were substantial social differences in physical stature in East-Germany. Social differences in height were greater in the East among females, and less among males than in the West. The difficulties experienced by the East-German population after 1961 is evident in the increase in social inequality of physical stature thereafter, as well as in the increasing gap relative to the height of the West-German population. After unification, however, there is a tendency for East-German males, but not of females, to catch up with their West-German counterparts

Reproductive Regrets Among a Population-Based Sample of U.S. Women

Women have many reproductive options, but little is known about their regrets regarding prior reproductive choices and outcomes. Guided by the life-course and stratified reproduction perspectives, this study draws on an open-ended question about reproductive regrets from wave I of the National Survey of Fertility Barriers, a representative telephone survey of reproductive aged U.S. women conducted from 2004 to 2006. The authors classified regrets into five broad categories: (1) none, (2) problematic fertility, (3) unfulfilled fertility desires, (4) family, and (5) pregnancy experiences. The authors conducted the analyses separately by motherhood status. Logistic regression analysis revealed that regardless of parental status, those who were older, had infertility, or were experiencing economic hardship were more likely to report reproductive regrets. The authors also investigated factors associated with the likelihood of expressing specific reproductive regrets. In general, the present findings confirm expectations based on the life-course and stratified reproduction perspectives

Change in Motherhood Status and Fertility Problem Identification: Implications for Changes in Life Satisfaction

Objective: To determine whether the association between changes in life satisfaction and becoming a mother (or not) depends on fertility problem identification status. Background: Evidence and symbolic interactionist theory suggest that, for women who initially perceive a fertility barrier, gaining the valued identity “mother” should be associated with increases and continuing to face a blocked goal (i.e., not becoming a mother) should be associated with decreases in life satisfaction. Method: This study used the nationally representative two-wave National Survey of Fertility Barriers to conduct a change-score analysis with chained multiple imputation. The focal dependent variable was change in life satisfaction. Focal independent variables were Wave 1 life satisfaction, fertility problem identification status, and birth between waves, controlling for stability and change in relationship status, talking to a doctor about how to get pregnant, religiosity, social support, importance of parenthood, importance of leisure, importance of work success, and economic hardship. Results: Among women who perceived a fertility problem at both waves, becoming a mother was associated with increased life satisfaction and not becoming a mother was associated with decreased life satisfaction. Women who gained or lost a fertility problem perception between waves but did not have a live birth experienced a gain in life satisfaction between waves, suggesting the relevance of the duration of fertility problem perception for change in life satisfaction

Relationship Satisfaction Among Infertile Couples: Implications of Gender and Self-Identification

We use path analysis to analyze heterosexual couples from the U.S. National Survey of Fertility Barriers, a probability-based sample of women and their male partners. We restrict the sample to couples in which the women are infertile. We estimate a path model of each partner’s relationship satisfaction on indicators of self-identifying as having a fertility problem or not at the individual and couple levels. We find a gender effect: for women, but not men, relationship satisfaction was significantly higher when neither partner self-identified as having a fertility problem. Women’s relationship satisfaction exerted a strong influence on their partners’ relationship satisfaction, but no similar association between men’s relationship satisfaction and their partner’s satisfaction was found. In infertile couples, higher levels of perceived social support are associated with higher levels of relationship satisfaction for women but not for men

Prediction of lethal and synthetically lethal knock-outs in regulatory networks

The complex interactions involved in regulation of a cell's function are captured by its interaction graph. More often than not, detailed knowledge about enhancing or suppressive regulatory influences and cooperative effects is lacking and merely the presence or absence of directed interactions is known. Here we investigate to which extent such reduced information allows to forecast the effect of a knock-out or a combination of knock-outs. Specifically we ask in how far the lethality of eliminating nodes may be predicted by their network centrality, such as degree and betweenness, without knowing the function of the system. The function is taken as the ability to reproduce a fixed point under a discrete Boolean dynamics. We investigate two types of stochastically generated networks: fully random networks and structures grown with a mechanism of node duplication and subsequent divergence of interactions. On all networks we find that the out-degree is a good predictor of the lethality of a single node knock-out. For knock-outs of node pairs, the fraction of successors shared between the two knocked-out nodes (out-overlap) is a good predictor of synthetic lethality. Out-degree and out-overlap are locally defined and computationally simple centrality measures that provide a predictive power close to the optimal predictor.Comment: published version, 10 pages, 6 figures, 2 tables; supplement at http://www.bioinf.uni-leipzig.de/publications/supplements/11-01

Phase transition between synchronous and asynchronous updating algorithms

We update a one-dimensional chain of Ising spins of length $L$ with algorithms which are parameterized by the probability $p$ for a certain site to get updated in one time step. The result of the update event itself is determined by the energy change due to the local change in the configuration. In this way we interpolate between the Metropolis algorithm at zero temperature for $p$ of the order of 1/L and for large $L$, and a synchronous deterministic updating procedure for $p=1$. As function of $p$ we observe a phase transition between the stationary states to which the algorithm drives the system. These are non-absorbing stationary states with antiferromagnetic domains for $p>p_c$, and absorbing states with ferromagnetic domains for $p\leq p_c$. This means that above this transition the stationary states have lost any remnants to the ferromagnetic Ising interaction. A measurement of the critical exponents shows that this transition belongs to the universality class of parity conservation.Comment: 5 pages, 3 figure

Kindlin-3 maintains marginal zone B cells but confines follicular B cell activation and differentiation

Integrin-mediated interactions between hematopoietic cells and their microenvironment are important for the development and function of immune cells. Here, the role of the integrin adaptor Kindlin-3 in B cell homeostasis is studied. Comparing the individual steps of B cell development in B cell-specific Kindlin-3 or alpha4 integrin knockout mice, we found in both conditions a phenotype of reduced late immature, mature, and recirculating B cells in the bone marrow. In the spleen, constitutive B cell-specific Kindlin-3 knockout caused a loss of marginal zone B cells and an unexpected expansion of follicular B cells. Alpha4 integrin deficiency did not induce this phenotype. In Kindlin-3 knockout B cells VLA-4 as well as LFA-1-mediated adhesion was abrogated, and short-term homing of these cells in vivo was redirected to the spleen. Upon inducible Kindlin-3 knockout, marginal zone B cells were lost due to defective retention within 2 weeks, while follicular B cell numbers were unaltered. Kindlin-3 deficient follicular B cells displayed higher IgD, CD40, CD44, CXCR5, and EBI2 levels, and elevated PI3K signaling upon CXCR5 stimulation. They also showed transcriptional signatures of spontaneous follicular B cell activation. This activation manifested in scattered germinal centers in situ, early plasmablasts differentiation, and signs of IgG class switch

Global Chromatin Domain Organization of the Drosophila Genome

In eukaryotes, neighboring genes can be packaged together in specific chromatin structures that ensure their coordinated expression. Examples of such multi-gene chromatin domains are well-documented, but a global view of the chromatin organization of eukaryotic genomes is lacking. To systematically identify multi-gene chromatin domains, we constructed a compendium of genome-scale binding maps for a broad panel of chromatin-associated proteins in Drosophila melanogaster. Next, we computationally analyzed this compendium for evidence of multi-gene chromatin domains using a novel statistical segmentation algorithm. We find that at least 50% of all fly genes are organized into chromatin domains, which often consist of dozens of genes. The domains are characterized by various known and novel combinations of chromatin proteins. The genes in many of the domains are coregulated during development and tend to have similar biological functions. Furthermore, during evolution fewer chromosomal rearrangements occur inside chromatin domains than outside domains. Our results indicate that a substantial portion of the Drosophila genome is packaged into functionally coherent, multi-gene chromatin domains. This has broad mechanistic implications for gene regulation and genome evolution

Improved Efficacy of Tafasitamab plus Lenalidomide versus Systemic Therapies for Relapsed/Refractory DLBCL: RE-MIND2, an Observational Retrospective Matched Cohort Study

PURPOSE: In RE-MIND2 (NCT04697160), patient-level outcomes from the L-MIND study (NCT02399085) of tafasitamab plus lenalidomide were retrospectively compared with patient-level matched observational cohorts treated with National Cancer Care Network (NCCN)/European Society for Medical Oncology (ESMO)-listed systemic therapies for relapsed/refractory diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: Data were collected from health records of eligible patients aged ≥18 years with histologically confirmed DLBCL who had received ≥2 systemic therapies for DLBCL (including ≥1 anti-CD20 therapy). Patients from L-MIND were matched with patients from the RE-MIND2 observational cohort using estimated propensity score-based 1:1 nearest-neighbor matching, balanced for nine covariates. The primary analysis compared tafasitamab plus lenalidomide with patients who received any systemic therapy for R/R DLBCL (pooled in one cohort) or bendamustine plus rituximab (BR) or rituximab plus gemcitabine and oxaliplatin (R-GemOx; as two distinct cohorts). The primary endpoint was overall survival (OS). Secondary endpoints included treatment response and time-to-event outcomes. RESULTS: In RE-MIND2, 3,454 patients were enrolled from 200 sites in North America, Europe, and Asia-Pacific. Strictly matched pairs of patients consisted of tafasitamab plus lenalidomide versus systemic therapies pooled (n = 76 pairs), versus BR (n = 75 pairs), and versus R-GemOx (n = 74 pairs). Significantly prolonged OS was reported with tafasitamab plus lenalidomide versus systemic pooled therapies [hazard ratios (HR): 0.55; P = 0.0068], BR (HR: 0.42; P < 0.0001), and R-GemOx (HR: 0.47; P = 0.0003). CONCLUSIONS: RE-MIND2, a retrospective observational study, met its primary endpoint, demonstrating prolonged OS with tafasitamab plus lenalidomide versus BR and R-GemOx. See related commentary by Cherng and Westin, p. 3908