A Zero-Parameter Extension of General Relativity with Varying Cosmological Constant

We provide a new extension of general relativity (GR) which has the remarkable property of being more constrained than GR plus a cosmological constant, having one less free parameter. This is implemented by allowing the cosmological constant to have a consistent space-time variation, through coding its dynamics in the torsion tensor. We demonstrate this mechanism by adding a `quasi-topological' term to the Einstein action, which naturally realizes a dynamical torsion with an automatic satisfaction of the Bianchi identities. Moreover, variation of the action with respect to this dynamical $\Lambda$ fixes it in terms of other variables, thus providing a scenario with less freedom than general relativity with a cosmological constant. Once matter is introduced, at least in the homogeneous and isotropic reduction, $\Lambda$ is uniquely determined by the field content of the model. We make an explicit construction using the Palatini formulation of GR and describe the striking properties of this new theory. We also highlight some possible extensions to the theory. A companion paper [1] explores the Friedmann--Robertson--Walker reduction for cosmology, and future work will study Solar System tests of the theory.Comment: Companion paper to arXiv:1905.10382. Minor updates to match published versio

The cosmology of minimal varying Lambda theories

Inserting a varying Lambda in Einstein's field equations can be made consistent with the Bianchi identities by allowing for torsion, without the need to add scalar field degrees of freedom. In the minimal such theory, Lambda is totally free and undetermined by the field equations in the absence of matter. Inclusion of matter ties Lambda algebraically to it, at least when homogeneity and isotropy are assumed, i.e. when there is no Weyl curvature. We show that Lambda is proportional to the matter density, with a proportionality constant depending on the equation of state. Unfortunately, the proportionality constant becomes infinite for pure radiation, ruling out the minimal theory prima facie despite of its novel internal consistency. It is possible to generalize the theory still without the addition of kinetic terms, leading to a new algebraically-enforced proportionality between Lambda and the matter density. Lambda and radiation may now coexist in a form consistent with Big Bang Nucleosynthesis, though this places strict constraints on the single free parameter of the theory, $\theta$. In the matter epoch Lambda behaves just like a dark matter component. Its density is proportional to the baryonic and/or dark matter, and its presence and gravitational effects would need to be included in accounting for the necessary dark matter in our Universe. This is a companion paper to Ref. [1] where the underlying gravitational theory is developed in detail.Comment: Companion paper to arXiv:1905.10380. Minor updates to match published versio

Efficient transcription through an intron requires the binding of an Sm-type U1 snRNP with intact stem loop II to the splice donor

The mechanism behind the positive action of introns upon transcription and the biological significance of this positive feedback remains unclear. Functional ablation of splice sites within an HIV-derived env cDNA significantly reduced transcription that was rescued by a U1 snRNA modified to bind to the mutated splice donor (SD). Using this model we further characterized both the U1 and pre-mRNA structural requirements for transcriptional enhancement. U1 snRNA rescued as a mature Sm-type snRNP with an intact stem loop II. Position and sequence context for U1-binding is crucial because a promoter proximal intron placed upstream of the mutated SD failed to rescue transcription. Furthermore, U1-rescue was independent of promoter and exon sequence and is partially replaced by the transcription elongation activator Tat, pointing to an intron-localized block in transcriptional elongation. Thus, transcriptional coupling of U1 snRNA binding to the SD may licence the polymerase for transcription through the intron

Discovery of Rubinite, Ca_3Ti^(3+)_2Si_3O_(12), a new Garnet Mineral in Refractory Inclusions from Carbonaceous Chondrites

During a nanomineralogy investigation of carbonaceous chondrites, a new Ti^(3+)-dominant garnet, named “rubinite,” Ca_3Ti^(3+)_2Si_3O_(12) with the Ia^3d garnet structure, was identified in five Ca-Al-rich inclusions (CAIs) from the CV3 chondrites Vigarano, Allende, and Efremovka. Field-emission scanning electron microscope, electron back-scatter diffraction, electron microprobe and ion microprobe techniques were used to characterize the chemistry, oxygen-isotope compositions, and structure of rubinite and associated phases. Synthetic Ca_3Ti^(3+)_2Si_3O_(12) garnet was reported by [1]. Here, we describe the first natural occurrences of rubinite as a refractory mineral in primitive meteorites. The mineral has been approved by the Commission on New Minerals, Nomenclature and Classification of the International Mineralogical Association (IMA 2016-110) [2]. The name honors Alan E. Rubin, a cosmochemist at University of California, Los Angeles (UCLA), USA, for his many contributions to cosmochemistry and meteorite research

Screening for Obstructive Sleep Apnea in Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force

Importance: Many adverse health outcomes are associated with obstructive sleep apnea (OSA). Objective: To review primary care-relevant evidence on screening adults for OSA, test accuracy, and treatment of OSA, to inform the US Preventive Services Task Force. Data Sources: MEDLINE, Cochrane Library, EMBASE, and trial registries through October 2015, references, and experts, with surveillance of the literature through October 5, 2016. Study Selection: English-language randomized clinical trials (RCTs); studies evaluating accuracy of screening questionnaires or prediction tools, diagnostic accuracy of portable monitors, or association between apnea-hypopnea index (AHI) and health outcomes among community-based participants. Data Extraction and Synthesis: Two investigators independently reviewed abstracts and full-text articles. When multiple similar studies were available, random-effects meta-analyses were conducted. Main Outcomes and Measures: Sensitivity, specificity, area under the curve (AUC), AHI, Epworth Sleepiness Scale (ESS) scores, blood pressure, mortality, cardiovascular events, motor vehicle crashes, quality of life, and harms. Results: A total of 110 studies were included (N = 46 188). No RCTs compared screening with no screening. In 2 studies (n = 702), the screening accuracy of the multivariable apnea prediction score followed by home portable monitor testing for detecting severe OSA syndrome (AHI ≥30 and ESS score >10) was AUC 0.80 (95% CI, 0.78 to 0.82) and 0.83 (95% CI, 0.77 to 0.90), respectively, but the studies oversampled high-risk participants and those with OSA and OSA syndrome. No studies prospectively evaluated screening tools to report calibration or clinical utility for improving health outcomes. Meta-analysis found that continuous positive airway pressure (CPAP) compared with sham was significantly associated with reduction of AHI (weighted mean difference [WMD], -33.8 [95% CI, -42.0 to -25.6]; 13 trials, 543 participants), excessive sleepiness assessed by ESS score (WMD, -2.0 [95% CI, -2.6 to -1.4]; 22 trials, 2721 participants), diurnal systolic blood pressure (WMD, -2.4 points [95% CI, -3.9 to -0.9]; 15 trials, 1190 participants), and diurnal diastolic blood pressure (WMD, -1.3 points [95% CI, -2.2 to -0.4]; 15 trials, 1190 participants). CPAP was associated with modest improvement in sleep-related quality of life (Cohen d, 0.28 [95% CI, 0.14 to 0.42]; 13 trials, 2325 participants). Mandibular advancement devices (MADs) and weight loss programs were also associated with reduced AHI and excessive sleepiness. Common adverse effects of CPAP and MADs included oral or nasal dryness, irritation, and pain, among others. In cohort studies, there was a consistent association between AHI and all-cause mortality. Conclusions and Relevance: There is uncertainty about the accuracy or clinical utility of all potential screening tools. Multiple treatments for OSA reduce AHI, ESS scores, and blood pressure. Trials of CPAP and other treatments have not established whether treatment reduces mortality or improves most other health outcomes, except for modest improvement in sleep-related quality of life

Attitudes toward children : distinguishing affection and stress

This project was supported by funding from the Economic and Social Research Council (ESRC) under grant agreement ES/P002463/1.Background Adults' views and behaviors toward children can vary from being supportive to shockingly abusive, and there are significant unanswered questions about the psychological factors underpinning this variability. Objective The present research examined the content of adults' attitudes toward children to address these questions. Method Ten studies (N?=?4702) identified the factor structure of adults' descriptions of babies, toddlers, and school-age children and examined how the resulting factors related to a range of external variables. Results Two factors emerged?affection toward children and stress elicited by them?and this factor structure was invariant across the United Kingdom, the United States, and South Africa. Affection uniquely captures emotional approach tendencies, concern for others, and broad positivity in evaluations, experiences, motivations, and donation behavior. Stress relates to emotional instability, emotional avoidance, and concern about disruptions to a self-oriented, structured life. The factors also predict distinct experiences in a challenging situation?home-parenting during COVID-19 lockdown?with affection explaining greater enjoyment and stress explaining greater perceived difficulty. Affection further predicts mentally visualizing children as pleasant and confident, whereas stress predicts mentally visualizing children as less innocent. Conclusions These findings offer fundamental new insights about social cognitive processes in adults that impact adult?child relationships and children's well-being.Publisher PDFPeer reviewe

ATR maintains chromosomal integrity during postnatal cerebellar neurogenesis and is required for medulloblastoma formation

Microcephaly and medulloblastoma may both result from mutations that compromise genomic stability. We report that ATR, which is mutated in the microcephalic disorder Seckel syndrome, sustains cerebellar growth by maintaining chromosomal integrity during postnatal neurogenesis. Atr deletion in cerebellar granule neuron progenitors (CGNPs) induced proliferation-associated DNA damage, p53 activation, apoptosis and cerebellar hypoplasia in mice. Co-deletions of either p53 or Bax and Bak prevented apoptosis in Atr-deleted CGNPs, but failed to fully rescue cerebellar growth. ATR-deficient CGNPs had impaired cell cycle checkpoint function and continued to proliferate, accumulating chromosomal abnormalities. RNA-Seq demonstrated that the transcriptional response to ATR-deficient proliferation was highly p53 dependent and markedly attenuated by p53 co-deletion. Acute ATR inhibition in vivo by nanoparticle-formulated VE-822 reproduced the developmental disruptions seen with Atr deletion. Genetic deletion of Atr blocked tumorigenesis in medulloblastoma-prone SmoM2 mice. Our data show that p53-driven apoptosis and cell cycle arrest – and, in the absence of p53, non-apoptotic cell death – redundantly limit growth in ATR-deficient progenitors. These mechanisms may be exploited for treatment of CGNP-derived medulloblastoma using ATR inhibition