Conformal p-branes as a Source of Structure in Spacetime

We discuss a model of a conformal p-brane interacting with the world volume metric and connection. The purpose of the model is to suggest a mechanism by which gravity coupled to p-branes leads to the formation of structure rather than homogeneity in spacetime. Furthermore, we show that the formation of structure is accompanied by the appearance of a multivalued cosmological constant, i.e., one which may take on different values in different domains, or cells, of spacetime. The above results apply to a broad class of non linear gravitational lagrangians as long as metric and connection on the p-brane manifold are treated as independent variables.Comment: 10 pages, ReVTeX, no figure

The Origin of Galactic Cosmic Rays

Motivated by recent measurements of the major components of the cosmic radiation around 10 TeV/nucleon and above, we discuss the phenomenology of a model in which there are two distinct kinds of cosmic ray accelerators in the galaxy. Comparison of the spectra of hydrogen and helium up to 100 TeV per nucleon suggests that these two elements do not have the same spectrum of magnetic rigidity over this entire region and that these two dominant elements therefore receive contributions from different sources.Comment: To be published in Physical Review D, 13 pages, with 3 figures, uuencode

On Higher Order Gravities, Their Analogy to GR, and Dimensional Dependent Version of Duff's Trace Anomaly Relation

An almost brief, though lengthy, review introduction about the long history of higher order gravities and their applications, as employed in the literature, is provided. We review the analogous procedure between higher order gravities and GR, as described in our previous works, in order to highlight its important achievements. Amongst which are presentation of an easy classification of higher order Lagrangians and its employment as a \emph{criteria} in order to distinguish correct metric theories of gravity. For example, it does not permit the inclusion of only one of the second order Lagrangians in \emph{isolation}. But, it does allow the inclusion of the cosmological term. We also discuss on the compatibility of our procedure and the Mach idea. We derive a dimensional dependent version of Duff's trace anomaly relation, which in \emph{four}-dimension is the same as the usual Duff relation. The Lanczos Lagrangian satisfies this new constraint in \emph{any} dimension. The square of the Weyl tensor identically satisfies it independent of dimension, however, this Lagrangian satisfies the previous relation only in three and four dimensions.Comment: 30 pages, added reference

A Systematic Review of Patients’ Values, Preferences, and Expectations for the Diagnosis and Treatment of Male Lower Urinary Tract Symptoms

Context: Understanding men's values and preferences in the context of personal, physical, emotional, relational, and social factors is important in optimising patient counselling, facilitating treatment decision-making, and improving guideline recommendations. Objective: To systematically review the available evidence regarding the values, preferences, and expectations of men towards the investigation and treatment (conservative, pharmacological, and surgical) of male lower urinary tract symptoms (LUTS). Evidence acquisition: We searched electronic databases until August 31, 2020 for quantitative and qualitative studies that reported values and preferences regarding the investigation and treatment of LUTS in men. We assessed the quality of evidence and risk of bias using the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) and GRADE Confidence in the Evidence from Reviews of Qualitative Research (CERQual) approaches. Evidence synthesis: We included 25 quantitative studies, three qualitative studies, and one mixed-methods study recruiting 9235 patients. Most men reported urodynamic testing to be acceptable, despite discomfort or embarrassment, as it significantly informs treatment decisions (low certainty evidence). Men preferred conservative and less risky treatment options, but the preference varied depending on baseline symptom severity and the risk/benefit characteristics of the treatment (moderate certainty). Men preferred pharmacological treatments with a low risk of erectile dysfunction and those especially improving urgency incontinence (moderate certainty). Other important preference considerations included reducing the risk of acute urinary retention or surgery (moderate certainty). Conclusions: Men prefer lower-risk management options that have fewer sexual side effects and are primarily effective at improving urgency incontinence and nocturia. Overall, the evidence was rated to be of low to moderate certainty. This review can facilitate the treatment decision-making process and improve the trustworthiness of guideline recommendations. Patient summary: We thoroughly reviewed the evidence addressing men's values and preferences regarding the management of urinary symptoms and found that minimising adverse effects is particularly important. Further research to understand other factors that matter to men is required. (C) 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.Peer reviewe

Randomized multicentre pilot study of sacubitril/valsartan versus irbesartan in patients with chronic kidney disease: United Kingdom Heart and Renal Protection (HARP)- III—rationale, trial design and baseline data

BACKGROUND: Patients with chronic kidney disease (CKD) are at risk of progression to end-stage renal disease and cardiovascular disease. Data from other populations and animal experiments suggest that neprilysin inhibition (which augments the natriuretic peptide system) may reduce these risks, but clinical trials among patients with CKD are required to test this hypothesis. METHODS: UK Heart and Renal Protection III (HARP-III) is a multicentre, double-blind, randomized controlled trial comparing sacubitril/valsartan 97/103 mg two times daily (an angiotensin receptor-neprilysin inhibitor) with irbesartan 300 mg one time daily among 414 patients with CKD. Patients ≥18 years of age with an estimated glomerular filtration rate (eGFR) of ≥45 but <60 mL/min/1.73 m2 and urine albumin:creatinine ratio (uACR) >20 mg/mmol or eGFR ≥20 but <45 mL/min/1.73 m2 (regardless of uACR) were invited to be screened. Following a 4- to 7-week pre-randomization single-blind placebo run-in phase (during which any current renin-angiotensin system inhibitors were stopped), willing and eligible participants were randomly assigned either sacubitril/valsartan or irbesartan and followed-up for 12 months. The primary aim was to compare the effects of sacubitril/valsartan and irbesartan on measured GFR after 12 months of therapy. Important secondary outcomes include effects on albuminuria, change in eGFR over time and the safety and tolerability of sacubitril/valsartan in CKD. RESULTS: Between November 2014 and January 2016, 620 patients attended a screening visit and 566 (91%) entered the pre-randomization run-in phase. Of these, 414 (73%) participants were randomized (mean age 63 years; 72% male). The mean eGFR was 34.0 mL/min/1.73 m2 and the median uACR was 58.5 mg/mmol. CONCLUSIONS: UK HARP-III will provide important information on the short-term effects of sacubitril/valsartan on renal function, tolerability and safety among patients with CKD

Eutectic colony formation: A phase field study

Eutectic two-phase cells, also known as eutectic colonies, are commonly observed during the solidification of ternary alloys when the composition is close to a binary eutectic valley. In analogy with the solidification cells formed in dilute binary alloys, colony formation is triggered by a morphological instability of a macroscopically planar eutectic solidification front due to the rejection by both solid phases of a ternary impurity that diffuses in the liquid. Here we develop a phase-field model of a binary eutectic with a dilute ternary impurity and we investigate by dynamical simulations both the initial linear regime of this instability, and the subsequent highly nonlinear evolution of the interface that leads to fully developed two-phase cells with a spacing much larger than the lamellar spacing. We find a good overall agreement with our recent linear stability analysis [M. Plapp and A. Karma, Phys. Rev. E 60, 6865 (1999)], which predicts a destabilization of the front by long-wavelength modes that may be stationary or oscillatory. A fine comparison, however, reveals that the assumption commonly attributed to Cahn that lamella grow perpendicular to the envelope of the solidification front is weakly violated in the phase-field simulations. We show that, even though weak, this violation has an important quantitative effect on the stability properties of the eutectic front. We also investigate the dynamics of fully developed colonies and find that the large-scale envelope of the composite eutectic front does not converge to a steady state, but exhibits cell elimination and tip-splitting events up to the largest times simulated.Comment: 18 pages, 18 EPS figures, RevTeX twocolumn, submitted to Phys. Rev.

Quantum geometrodynamics: whence, whither?

Quantum geometrodynamics is canonical quantum gravity with the three-metric as the configuration variable. Its central equation is the Wheeler--DeWitt equation. Here I give an overview of the status of this approach. The issues discussed include the problem of time, the relation to the covariant theory, the semiclassical approximation as well as applications to black holes and cosmology. I conclude that quantum geometrodynamics is still a viable approach and provides insights into both the conceptual and technical aspects of quantum gravity.Comment: 25 pages; invited contribution for the Proceedings of the seminar "Quantum Gravity: Challenges and Perspectives", Bad Honnef, Germany, April 200

The ecology of sex explains patterns of helping in arthropod societies

Authors thank the Natural Sciences and Engineering Research Council of Canada (NGD), the Clarendon Fund (NGD) and the Natural Environment Research Council (LR, NE/K009516/1; AG, NE/K009524/1) for funding.Across arthropod societies, sib-rearing (e.g. nursing or nest defence) may be provided by females, by males or by both sexes. According to Hamilton's ‘haplodiploidy hypothesis’, this diversity reflects the relatedness consequences of diploid vs. haplodiploid inheritance. However, an alternative ‘preadaptation hypothesis’ instead emphasises an interplay of ecology and the co-option of ancestral, sexually dimorphic traits for sib-rearing. The preadaptation hypothesis has recently received empirical support, but remains to be formalised. Here, we mathematically model the coevolution of sex-specific helping and sex allocation, contrasting these hypotheses. We find that ploidy per se has little effect. Rather, the ecology of sex shapes patterns of helping: sex-specific preadaptation strongly influences who helps; a freely adjustable sex ratio magnifies sex biases and promotes helping; and sib-mating, promiscuity, and reproductive autonomy also modulate the sex and abundance of helpers. An empirical survey reveals that patterns of sex-specific helping in arthropod taxa are consistent with the preadaptation hypothesis.Publisher PDFPeer reviewe

A perspective on the landscape problem

I discuss the historical roots of the landscape problem and propose criteria for its successful resolution. This provides a perspective to evaluate the possibility to solve it in several of the speculative cosmological scenarios under study including eternal inflation, cosmological natural selection and cyclic cosmologies.Comment: Invited contribution for a special issue of Foundations of Physics titled: Forty Years Of String Theory: Reflecting On the Foundations. 31 pages, no figure

Detecting new microRNAs in human osteoarthritic chondrocytes identifies miR-3085 as a human, chondrocyte-selective, microRNA

Objective: To use deep sequencing to identify novel microRNAs in human osteoarthritic cartilage which have a functional role in chondrocyte phenotype or function. Design: A small RNA library was prepared from human osteoarthritic primary chondrocytes using in-house adaptors and analysed by Illumina sequencing. Novel candidate microRNAs were validated by northern blot and qRT-PCR. Expression was measured in cartilage models. Targets of novel candidates were identified by microarray and computational analysis, validated using 3’-UTR-luciferase reporter plasmids. Protein levels were assessed by western blot and functional analysis by cell adhesion. Results: We identified 990 known microRNAs and 1621 potential novel microRNAs in human osteoarthritic chondrocytes, 60 of the latter were expressed in all samples assayed. MicroRNA-140-3p was the most highly expressed microRNA in osteoarthritic cartilage. Sixteen novel candidate microRNAs were analysed further, of which 6 remained after northern blot analysis. Three novel microRNAs were regulated across models of chondrogenesis, chondrocyte differentiation or cartilage injury. One sequence (novel #11), annotated in rodents as microRNA-3085-3p, was preferentially expressed in cartilage, dependent on chondrocyte differentiation and, in man, is located in an intron of the cartilage-expressed gene CRTAC-1. This microRNA was shown to target the ITGA5 gene directly (which encodes integrin alpha5) and inhibited adhesion to fibronectin (dependent on alpha5beta1 integrin). Conclusion: Deep sequencing has uncovered many potential microRNA candidates expressed in human cartilage. At least three of these show potential functional interest in cartilage homeostasis and osteoarthritis. Particularly, novel #11 (microRNA-3085-3p) which has been identified for the first time in man