Adult attachment style across individuals and role-relationships: Avoidance is relationship-specific, but anxiety shows greater generalizability

A generalisability study examined the hypotheses that avoidant attachment, reflecting the representation of others, should be more relationship-specific (vary across relationships more than across individuals), while attachment anxiety, reflecting self-representation, should be more generalisable across a person’s relationships. College students responded to 6-item questionnaire measures of these variables for 5 relationships (mother, father, best same-gender friend, romantic partner or best opposite-gender friend, other close person), on 3 (N = 120) or 2 (N = 77) occasions separated by a few weeks. Results supported the hypotheses, with the person variance component being larger than the relationship-specific component for anxiety, and the opposite happening for avoidance. Anxiety therefore seems not to be as relationship-specific as previous research suggested. Possible reasons for discrepancies between the current and previous studies are discussed

Transport time scales in soil erosion modelling

Unlike sediment transport in rivers, erosion of agricultural soil must overcome its cohesive strength to move soil particles into suspension. Soil particle size variability also leads to fall velocities covering many orders of magnitude, and hence to different suspended travel distances in overland flow. Consequently, there is a large range of inherent time scales involved in transport of eroded soil. For conditions where there is a constant rainfall rate and detachment is the dominant erosion mechanism, we use the Hairsine-Rose (HR) model to analyze these timescales, to determine their magnitude (bounds) and to provide simple approximations for them. We show that each particle size produces both fast and slow timescales. The fast timescale controls the rapid adjustment away from experimental initial conditions – this happens so quickly that it cannot be measured in practice. The slow time scales control the subsequent transition to steady state and are so large that true steady state is rarely achieved in laboratory experiments. Both the fastest and slowest time scales are governed by the largest particle size class. Physically, these correspond to the rate of vertical movement between suspension and the soil bed, and the time to achieve steady state, respectively. For typical distributions of size classes, we also find that there is often a single dominant time scale that governs the growth in the total mass of sediment in the non-cohesive deposited layer. This finding allows a considerable simplification of the HR model leading to analytical expressions for the evolution of suspended and deposited layer concentrations

The price of rapid exit in venture capital-backed IPOs

This paper proposes an explanation for two empirical puzzles surrounding initial public offerings (IPOs). Firstly, it is well documented that IPO underpricing increases during “hot issue” periods. Secondly, venture capital (VC) backed IPOs are less underpriced than non-venture capital backed IPOs during normal periods of activity, but the reverse is true during hot issue periods: VC backed IPOs are more underpriced than non-VC backed ones. This paper shows that when IPOs are driven by the initial investor’s desire to exit from an existing investment in order to finance a new venture, both the value of the new venture and the value of the existing firm to be sold in the IPO drive the investor’s choice of price and fraction of shares sold in the IPO. When this is the case, the availability of attractive new ventures increases equilibrium underpricing, which is what we observe during hot issue periods. Moreover, I show that underpricing is affected by the severity of the moral hazard problem between an investor and the firm’s manager. In the presence of a moral hazard problem the degree of equilibrium underpricing is more sensitive to changes in the value of the new venture. This can explain why venture capitalists, who often finance firms with more severe moral hazard problems, underprice IPOs less in normal periods, but underprice more strongly during hot issue periods. Further empirical implications relating the fraction of shares sold and the degree of underpricing are presented

Distinct Assemblies of Heterodimeric Cytokine Receptors Govern Stemness Programs in Leukemia

Published first May 16, 2023Leukemia stem cells (LSC) possess distinct self-renewal and arrested differentiation properties that are responsible for disease emergence, therapy failure, and recurrence in acute myeloid leukemia (AML). Despite AML displaying extensive biological and clinical heterogeneity, LSC with high interleukin-3 receptor (IL3R) levels are a constant yet puzzling feature, as this receptor lacks tyrosine kinase activity. Here, we show that the heterodimeric IL3Rα/βc receptor assembles into hexamers and dodecamers through a unique interface in the 3D structure, where high IL3Rα/βc ratios bias hexamer formation. Importantly, receptor stoichiometry is clinically relevant as it varies across the individual cells in the AML hierarchy, in which high IL3Rα/βc ratios in LSCs drive hexamer-mediated stemness programs and poor patient survival, while low ratios mediate differentiation. Our study establishes a new paradigm in which alternative cytokine receptor stoichiometries differentially regulate cell fate, a signaling mechanism that may be generalizable to other transformed cellular hierarchies and of potential therapeutic significance.Winnie L. Kan, Urmi Dhagat, Kerstin B. Kaufmann, Timothy R. Hercus, Tracy L. Nero, Andy G.X. Zeng, John Toubia, Emma F. Barry, Sophie E. Broughton, Guillermo A. Gomez, Brooks A. Benard, Mara Dottore, Karen S. Cheung Tung Shing, Héléna Boutzen, Saumya E. Samaraweera, Kaylene J. Simpson, Liqing Jin, Gregory J. Goodall, C. Glenn Begley, Daniel Thomas, Paul G. Ekert, Denis Tvorogov, Richard J. D, Andrea, John E. Dick, Michael W. Parker, and Angel F. Lope

The mammalian gene function resource: The International Knockout Mouse Consortium

In 2007, the International Knockout Mouse Consortium (IKMC) made the ambitious promise to generate mutations in virtually every protein-coding gene of the mouse genome in a concerted worldwide action. Now, 5 years later, the IKMC members have developed highthroughput gene trapping and, in particular, gene-targeting pipelines and generated more than 17,400 mutant murine embryonic stem (ES) cell clones and more than 1,700 mutant mouse strains, most of them conditional. A common IKMC web portal (www.knockoutmouse.org) has been established, allowing easy access to this unparalleled biological resource. The IKMC materials considerably enhance functional gene annotation of the mammalian genome and will have a major impact on future biomedical research

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

ACE and UCP2 gene polymorphisms and their association with baseline and exercise-related changes in the functional performance of older adults

Maintaining high levels of physical function is an important aspect of successful ageing. While muscle mass and strength contribute to functional performance in older adults, little is known about the possible genetic basis for the heterogeneity of physical function in older adults and in how older adults respond to exercise. Two genes that have possible roles in determining levels of muscle mass, strength and function in young and older adults are angiotensin-converting enzyme (ACE) and mitochondrial uncoupling protein 2 (UCP2). This study examined whether polymorphisms in these two individual genes were associated with baseline functional performance levels and/or the training-related changes following exercise in previously untrained older adults. Five-eight Caucasian older adults (mean age 69.8 years) with no recent history of resistance training enrolled in a 12 week program of resistance, balance and cardiovascular exercises aimed at improving functional performance. Performance in 6 functional tasks was recorded at baseline and after 12 weeks. Genomic DNA was assayed for the ACE intron 16 insertion/deletion (I/D) and the UCP2 G-866A polymorphism. Baseline differences among genotype groups were tested using analysis of variance. Genotype differences in absolute and relative changes in physical function among the exercisers were tested using a general linear model, adjusting for age and gender. The genotype frequencies for each of the studied polymorphisms conformed to the Hardy-Weinberg equilibrium. The ACE I/D genotype was significantly associated with mean baseline measures of handgrip strength (II 30.9 ± 3.01 v. ID 31.7 ± 1.48 v. DD 29.3 ± 2.18 kg, p < 0.001), 8ft Up and Go time (II 6.45 ± 0.48 v. ID/DD 4.41 ± 0.19 s, p < 0.001) and 6 min walk distance (II 458 ± 28.7 v. ID/DD 546 ± 12.1m, p = 0.008). The UCP2 G-866A genotype was also associated with baseline 8ft Up and Go time (GG 5.45 ± 0.35 v. GA 4.47 ± 0.26 v. AA 3.89 ± 0.71 s, p = 0.045). After 12 weeks of training, a significant difference between UCP2 G-886A genotype groups for change in 8ft Up and Go time was detected (GG −0.68 ± 0.17 v. GA −0.10 ± 0.14 v. AA +0.05 ± 0.31 s, p = 0.023). While several interesting and possibly consistent associations with older adults’ baseline functional performance were found for the ACE and UCP2 polymorphisms, we found no strong evidence of genetic associations with exercise responses in this study. The relative equivalence of some of these training-response findings to the literature may have reflected the current study’s focus on physical function rather than just strength, the relatively high levels of baseline function for some genotype groups as well as the greater statistical power for detecting baseline differences than the training-related changes

Metacognition and learning in spoken dialogue computer tutoring

We investigate whether four metacognitive metrics derived from student correctness and uncertainty values are predictive of student learning in a fully automated spoken dialogue computer tutoring corpus. We previously showed that these metrics predicted learning in a comparable wizarded corpus, where a human wizard performed the speech recognition and correctness and uncertainty annotation. Our results show that three of the four metacognitive metrics remain predictive of learning even in the presence of noise due to automatic speech recognition and automatic correctness and uncertainty annotation. We conclude that our results can be used to inform a future enhancement of our fully automated system to track and remediate student metacognition and thereby further improve learning. © Springer-Verlag Berlin Heidelberg 2010