Non-locality in quantum field theory due to general relativity

We show that general relativity coupled to a quantum field theory generically leads to non-local effects in the matter sector. These non-local effects can be described by non-local higher dimensional operators which remarkably have an approximate shift symmetry. When applied to inflationary models, our results imply that small non-Gaussianities are a generic feature of models based on general relativity coupled to matter fields. However, these effects are too small to be observable in the cosmic microwave background

Avoidance of reporter assay distortions from fused dual reporters

Positioning test sequences between fused reporters permits monitoring of both translation levels and framing, before and after the test sequence. Many studies, including those on recoding such as productive ribosomal frameshifting and stop codon readthrough, use distinguishable luciferases or fluorescent proteins, as reporters. Occasional distortions, due to test sequence product interference with the individual reporter activities or stabilities, are here shown to be avoidable by the introduction of tandem StopGo sequences (2A) flanking the test sequence. Using this new vector system (pSGDluc), we provide evidence for the use of a 3’ stem loop stimulator for $\textit{ACP2}$ readthrough, but failed to detect the reported $\textit{VEGFA}$ readthrough.This work was supported by grants from Science Foundation Ireland (12/IP/1492 and 13/1A/1853 to J.F.A.), National Institutes of Health (R01GM114291 and R21ES022716 to M.T.H.), Wellcome Trust (106207 to A.E.F.) and the European Research Council (646891 to A.E.F.)

Improving public services through open data: public toilets

Bichard’s work for the TACT3 project (Bichard REF Output 3) found that UK toilet provision is not centrally collated and no national map or database of toilets exists. In contrast, the UK government’s white paper Open Public Services (2011) emphasised its commitment to incorporating the use of Open Data in public services provision that could be tailored to community preferences, and therefore be more sustainable. Incorporating Open Data on public toilet provision, Bichard and Knight (RCA) developed The Great British Public Toilet Map (GBPTM). Whilst a number of other websites and applications map toilets by ‘crowd surfing’, GBPTM is entirely populated by Open Data, and not only uses the data as information for users, but informs members of the public that such information is available and accessible for their use. This paper presents the development of the GBPTM, including inclusive design research and studies that compare accuracy of information directly provided by users with Open Data collected by local authorities. It suggests that, to meet the health and well-being of an ageing population, a sustainable and cost-effective solution must be found for ‘publicly accessible’ toilet provision, including opening up provision beyond that ‘for customers only’ and providing accurate information on current public provision. The paper highlights the barriers encountered in the production of Open Data by local authorities. A review of the paper in the journal Civil Engineering (May 2013) described the design of the GBPTM as a ‘simple and elegant solution’. The development of a digital output and an understanding of digitally based research led to Bichard’s successful submission to an EPSRC Digital Economy sandpit, in which she developed an interdisciplinary project with the Universities of Newcastle, Bournemouth and the West of England. The project, Family Rituals 2.0, secured £750,000 in research funding with Bichard as co-investigator (2013–15)

Gravitational effective action at second order in curvature and gravitational waves

We consider the full effective theory for quantum gravity at second order in curvature including non-local terms. We show that the theory contains two new degrees of freedom beyond the massless graviton: namely a massive spin-2 ghost and a massive scalar field. Furthermore, we show that it is impossible to fine-tune the parameters of the effective action to eliminate completely the classical spin-2 ghost because of the non-local terms in the effective action. Being a classical field, it is not clear anyway that this ghost is problematic. It simply implies a repulsive contribution to Newton’s potential. We then consider how to extract the parameters of the effective action and show that it is possible to measure, at least in principle, the parameters of the local terms independently of each other using a combination of observations of gravitational waves and measurements performed by pendulum type experiments searching for deviations of Newton’s potential

Evaluation of the efficacy and safety of text messages targeting adherence to cardiovascular medications in secondary prevention: the txt2heart Colombia randomised controlled trial (Preprint)

Background: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality in the world. Prevalence is estimated at around 100 million patients worldwide. There is evidence that antiplatelet agents and antihypertensive medication reduce the risk of new vascular events in this population, but treatment adherence is very low. Objective: We developed an intervention based on behavioral modification techniques delivered via mobile short message services (SMS) to increase the adherence to pharmacologic treatment on patients with prior history of ASCVD. Methods: We conducted a randomized controlled clinical trial for patients with a prior diagnosis of cardiovascular event such as acute myocardial infarction, unstable angina, cerebrovascular disease or peripheral artery disease in one centre in Colombia. Patients randomized to the intervention arm were assigned to receive SMS daily for the first 4 weeks, five SMS on week 5: three SMS per week from week 6, and one SMS from 8th week until 52nd week. Patients in the control arm received a monthly SMS reminding them of the next study appointment, requesting information about changes in phone number, thanking them for participating in the study and reminding them of the importance of the study. Primary endpoint was change in Low Density Lipoprotein-Cholesterol (LDL-C) and the secondary endpoints were change in thromboxane B2 levels, heart rate, systolic and diastolic blood pressure. Medication adherence was measured with the Medication Adherence Report Scale (MARS 5), mortality and new cardiac hospitalization were assessed at one year end point. A logistic regression analysis and bivariate testing was performed. Results: Nine hundred and thirty patients were randomized, 805 (87%) completed follow up, and were analyzed for the primary endpoint. There was no difference between arms in change of LDL-C at 12 months (P=.41). or for any of the secondary outcomes. No adverse events were reported. Conclusions: In our study we did not find evidence that a behavior modification intervention delivered by SMS improved LDL-C, blood pressure levels or adherence at 12 months. More research is needed to evaluate whether different SMS strategies including personalized messages and with different timing are effective; future studies should include mixed methods to understand better why, for whom and in which context (e.g. health system, social environment) SMS interventions work (or not) to improve adherence in patients with ASCVD. Clinical Trial: Clinicaltrial.gov NCT03098186. Date of registration: March 31st 201

Viroids: survivors from the RNA world?

[EN] Because RNA can be a carrier of genetic information and a biocatalyst, there is a consensus that it emerged before DNA and proteins, which eventually assumed these roles and relegated RNA to intermediate functions. If such a scenario¿the so-calledRNAworld¿existed,wemight hope to find its relics in our presentworld. The properties of viroids that make them candidates for being survivors of the RNA world include those expected for primitive RNA replicons: (a) small size imposed by error-prone replication, (b) high G + C content to increase replication fidelity, (c) circular structure for assuring complete replication without genomic tags, (d ) structural periodicity for modular assembly into enlarged genomes, (e) lack of protein-coding ability consistent with a ribosome-free habitat, and ( f ) replication mediated in some by ribozymes, the fingerprint of the RNA world. With the advent of DNA and proteins, those protoviroids lost some abilities and became the plant parasites we now know.R.F. has received funding by grant BFU2011-28443 from Ministerio de Economia y Competititvidad (MINECO, Spain), R.S. by grants BFU2011-25271 (MINECO) and ERC-2011-StG-281191-VIRMUT (European Research Council), and S.F.E. by grant BFU2012-30805 (MINECO). P.S. has been supported by postdoctoral contracts from Generalitat Valenciana (APOSTD/2010, program VALi+d) and MINECO (program Juan de la Cierva).Flores Pedauye, R.; Gago Zachert, SP.; Serra Alfonso, P.; Sanjuan Verdeguer, R.; Elena Fito, SF. (2014). Viroids: survivors from the RNA world?. Annual Review of Microbiology. 68:395-414. https://doi.org/10.1146/annurev-micro-091313-103416S3954146

Translation initiation from conserved non-AUG codons provides additional layers of regulation and coding capacity

Neurospora crassa cpc-1 and Saccharomyces cerevisiae GCN4 are homologs specifying transcription activators that drive the transcriptional response to amino acid limitation. The cpc-1 mRNA contains two upstream open reading frames (uORFs) in its >700 nt 5’-leader and its expression is controlled at the level of translation in response to amino acid starvation. We used N. crassa cell-free extracts and obtained data indicating that cpc-1 uORF1 and uORF2 are functionally analogous to GCN4 uORF1 and uORF4 in controlling translation. We also found that the 5’ region upstream of the main coding sequence of the cpc-1 mRNA extends for more than 700 nucleotides without any in-frame stop codon. For 100 cpc-1 homologs from Pezizomycotina and from selected Basidiomycota, 5’ conserved extensions of the CPC1 reading frame are also observed. Multiple non-AUG near-cognate codons (NCCs) in the CPC1 reading frame upstream of uORF2, some deeply conserved, could potentially initiate translation. At least four NCCs initiated translation in vitro. In vivo data were consistent with initiation at NCCs to produce N-terminally extended N. crassa CPC1 isoforms. The pivotal role played by CPC1, combined with its translational regulation by uORFs and NCC utilization, underscore the emerging significance of non-canonical initiation events in controlling gene expression.This work was supported by National Institutes of Health grants (GM068087 to J.C.D., D.B.-P., M.F., and M.S.S. and GM47498 to M.S.S.), the Science Foundation Ireland (grant 08/IN.1/B1889 to J.F.A.), the Wellcome Trust (grant 106207) to A.E.F., and the Texas A&M Institute for Advanced Study (to J.C.D., D.B.-P., and M.S.S.). Funding for the open access charge was from the National Institutes of Health

Target and reality of adjuvant endocrine therapy in postmenopausal patients with invasive breast cancer

Previous research evaluating the use of adjuvant endocrine therapy among postmenopausal breast cancer patients showed with 15–50% wide ranges of non-adherence rates. We evaluated this issue by analysing an unselected study group comprising of 325 postmenopausal women, diagnosed from 1997 to 2003 with hormonal receptor-positive invasive breast cancer. The different clinical situations that led to the discontinuation of adjuvant endocrine therapy were clearly defined and differentiated: non-adherence was not simply the act of stopping medication, but rather the manifestation of an intentional behaviour of the patient. Of the 287 patients who initiated endocrine therapy, 191 (66.6%) fully completed this treatment. Thirty-one patients (10.8%) showed non-adherence to therapy. Patients who had follow-up with a general practitioner, rather than in an oncologic unit, were more likely to be non-adherent (P=0.0088). Of 25 patients who changed medication due to therapy-related adverse effects, 20 (80%) patients fully completed the therapy after drug change. In adjuvant endocrine therapy, a lowering of the non-adherence rate to 10.8%, the lowest reported in the literature, is realistic when patients are cared for by a specialised oncologic unit focusing on the individual needs of the patients

Therapeutic Radionuclides: Making the Right Choice

Recently, there has been a resurgence of interest in nuclear medicine therapeutic procedures. Using unsealed sources for therapy is not a new concept; it has been around since the beginnings of nuclear medicine. Treatment of thyroid disorders with radioiodine is a classic example. The availability of radionuclides with suitable therapeutic properties for specific applications, as well as methods for their selective targeting to diseased tissue have, however, remained the main obstacles for therapy to assume a more widespread role in nuclear medicine. Nonetheless, a number of new techniques that have recently emerged, (e.g., tumor therapy with radiolabeled monoclonal antibodies, treatment of metastatic bone pain, etc.) appear to have provided a substantial impetus to research on production of new therapeutic radionuclides. Although there are a number of new therapeutic approaches requiring specific radionuclides, only selected broad areas will be used as examples in this article

Effectiveness of Terbutaline Pump for the Prevention of Preterm Birth. A Systematic Review and Meta-Analysis

Subcutaneous terbutaline (SQ terbutaline) infusion by pump is used in pregnant women as a prolonged (beyond 48-72 h) maintenance tocolytic following acute treatment of preterm contractions. The effectiveness and safety of this maintenance tocolysis have not been clearly established. We aimed to systematically evaluate the effectiveness and safety of subcutaneous (SQ) terbutaline infusion by pump for maintenance tocolysis.MEDLINE, EMBASE, CINAHL, the Cochrane Library, the Centre for Reviews and Dissemination databases, post-marketing surveillance data and grey literature were searched up to April 2011 for relevant experimental and observational studies. Two randomized trials, one nonrandomized trial, and 11 observational studies met inclusion criteria. Non-comparative studies were considered only for pump-related harms. We excluded case-reports but sought FDA summaries of post-marketing surveillance data. Non-English records without an English abstract were excluded. Evidence of low strength from observational studies with risk of bias favored SQ terbutaline pump for the outcomes of delivery at <32 and <37 weeks, mean days of pregnancy prolongation, and neonatal death. Observational studies of medium to high risk of bias also demonstrated benefit for other surrogate outcomes, such as birthweight and neonatal intensive care unit (NICU) admission. Several cases of maternal deaths and maternal cardiovascular events have been reported in patients receiving terbutaline tocolysis.Although evidence suggests that pump therapy may be beneficial as maintenance tocolysis, our confidence in its validity and reproducibility is low, suggesting that its use should be limited to the research setting. Concerns regarding safety of therapy persist