Dynamical Generation of Spacetime Signature by Massive Quantum Fields on a Topologically Non-Trivial Background

The effective potential for a dynamical Wick field (dynamical signature) induced by the quantum effects of massive fields on a topologically non-trivial $D$ dimensional background is considered. It is shown that when the radius of the compactified dimension is very small compared with $\Lambda^{1/2}$ (where $\Lambda$ is a proper-time cutoff), a flat metric with Lorentzian signature is preferred on ${\bf R}^4 \times {\bf S}^1$. When the compactification radius becomes larger a careful analysis of the 1-loop effective potential indicates that a Lorentzian signature is preferred in both $D=6$ and $D=4$ and that these results are relatively stable under metrical perturbations

An operational workflow for producing periodic estimates of species occupancy at national scales

Policy makers require high-level summaries of biodiversity change. However, deriving such summaries from raw biodiversity data is a complex process involving several intermediary stages. In this paper, we describe an operational workflow for generating annual estimates of species occupancy at national scales from raw species occurrence data, which can be used to construct a range of policy-relevant biodiversity indicators. We describe the workflow in detail: from data acquisition, data assessment and data manipulation, through modelling, model evaluation, application and dissemination. At each stage, we draw on our experience developing and applying the workflow for almost a decade to outline the challenges that analysts might face. These challenges span many areas of ecology, taxonomy, data science, computing and statistics. In our case, the principal output of the workflow is annual estimates of occupancy, with measures of uncertainty, for over 5000 species in each of several defined ‘regions’ (e.g. countries, protected areas, etc.) of the UK from 1970 to 2019. This data product corresponds closely to the notion of a species distribution Essential Biodiversity Variable (EBV). Throughout the paper, we highlight methodologies that might not be applicable outside of the UK and suggest alternatives. We also highlight areas where the workflow can be improved; in particular, methods are needed to mitigate and communicate the risk of bias arising from the lack of representativeness that is typical of biodiversity data. Finally, we revisit the ‘ideal’ and ‘minimal’ criteria for species distribution EBVs laid out in previous contributions and pose some outstanding questions that should be addressed as a matter of priority. Going forward, we hope that this paper acts as a template for research groups around the world seeking to develop similar data products

ISOGAL: A deep survey of the obscured inner Milky Way with ISO at 7 and 15 micron and with DENIS in the near-infrared

The ISOGAL project is an infrared survey of specific regions sampling the Galactic Plane selected to provide information on Galactic structure,stellar populations,stellar mass-loss and the recent star formation history of the inner disk and Bulge of the Galaxy. ISOGAL combines 7 and 15 micron ISOCAM observations - with a resolution of 6'' at worst - with DENIS IJKs data to determine the nature of the sources and theinterstellar extinction. We have observed about 16 square degrees with a sensitivity approaching 10-20mJy, detecting ~10^5 sources,mostly AGB stars,red giants and young stars. The main features of the ISOGAL survey and the observations are summarized in this paper,together with a brief discussion of data processing and quality. The primary ISOGAL products are described briefly (a full description is given in Schuller et al. 2003, astro-ph/0304309): viz. the images and theISOGAL-DENIS five-wavelength point source catalogue. The main scientific results already derived or in progress are summarized. These include astrometrically calibrated 7 and 15um images,determining structures of resolved sources; identification and properties of interstellar dark clouds; quantification of the infrared extinction law and source dereddening; analysis of red giant and (especially) AGB stellar populations in the central Bulge,determining luminosity,presence of circumstellar dust and mass--loss rate,and source classification,supplemented in some cases by ISO/CVF spectroscopy; detection of young stellar objects of diverse types,especially in the inner Bulge with information about the present and recent star formation rate; identification of foreground sources with mid-IR excess. These results are the subject of about 25 refereed papers published or in preparation.Comment: A&A in press. 19 pages,10 Ps figures; problems with figures fixe

Overcoming Wnt–β-catenin dependent anticancer therapy resistance in leukaemia stem cells

Leukaemia stem cells (LSCs) underlie cancer therapy resistance but targeting these cells remains difficult. The Wnt–β-catenin and PI3K–Akt pathways cooperate to promote tumorigenesis and resistance to therapy. In a mouse model in which both pathways are activated in stem and progenitor cells, LSCs expanded under chemotherapy-induced stress. Since Akt can activate β-catenin, inhibiting this interaction might target therapy-resistant LSCs. High-throughput screening identified doxorubicin (DXR) as an inhibitor of the Akt–β-catenin interaction at low doses. Here we repurposed DXR as a targeted inhibitor rather than a broadly cytotoxic chemotherapy. Targeted DXR reduced Akt-activated β-catenin levels in chemoresistant LSCs and reduced LSC tumorigenic activity. Mechanistically, β-catenin binds multiple immune-checkpoint gene loci, and targeted DXR treatment inhibited expression of multiple immune checkpoints specifically in LSCs, including PD-L1, TIM3 and CD24. Overall, LSCs exhibit distinct properties of immune resistance that are reduced by inhibiting Akt-activated β-catenin. These findings suggest a strategy for overcoming cancer therapy resistance and immune escape

Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions

While germline copy-number variants (CNVs) contribute to schizophrenia (SCZ) risk, the contribution of somatic CNVs (sCNVs)—present in some but not all cells—remains unknown. We identified sCNVs using blood-derived genotype arrays from 12,834 SCZ cases and 11,648 controls, filtering sCNVs at loci recurrently mutated in clonal blood disorders. Likely early-developmental sCNVs were more common in cases (0.91%) than controls (0.51%, p = 2.68e−4), with recurrent somatic deletions of exons 1–5 of the NRXN1 gene in five SCZ cases. Hi-C maps revealed ectopic, allele-specific loops forming between a potential cryptic promoter and non-coding cis-regulatory elements upon 5′ deletions in NRXN1. We also observed recurrent intragenic deletions of ABCB11, encoding a transporter implicated in anti-psychotic response, in five treatment-resistant SCZ cases and showed that ABCB11 is specifically enriched in neurons forming mesocortical and mesolimbic dopaminergic projections. Our results indicate potential roles of sCNVs in SCZ risk

Differences Between Sexually And Non-Sexually Abused Children In Their Behavioral Responses To Anatomically Correct Dolls

The purpose of this study was to determine whether there were differences between sexually and non-sexually abused children in their behavioral responses to anatomically correct dolls.Volunteer subjects were 16 5-8 year old non abused female children and 16 5-8 year old sexually abused female children. A standard protocol was utilized for the introduction of anatomically correct dolls. After a warm-up period between the child and the examiner, a family of four anatomically correct dolls was presented to the child. The child was told that the dolls were a little different than dolls she may have seen before and that they had all of their body parts. Children were left alone with the dolls for a period of five minutes and instructed to play with the dolls and to change their clothes. The examiner returned and asked the child to tell a story about the family of dolls for a period of three minutes. The entire session was video-taped and the behaviors were rated by two raters using a specially designed behavior checklist. Four behaviors were examined in the Alone Condition and in the Storytelling Condition. These behaviors were; Freeplay, Avoidance, Aggression, and Private Parts References. T-tests were computed to examine the differences between abused and non abused children.The results of this study support the contention that there are differences in how sexually abused and non abused children respond behaviorally to anatomically correct dolls when asked to tell stories about the dolls and while the children played alone with the dolls. Sexually abused children exhibited significantly less Freeplay behavior than non abused children perhaps because more energy was spent in avoiding the dolls when in the presence of an adult. Abused children were also more preoccupied with Private Parts while alone with the dolls. Both sexually and non sexually abused children exhibited few private parts references in the presence of an adult leading to the conclusion that children were suppressing in the presence of an adult. An incidental finding was that many therapists were uncomfortable using anatomically correct dolls and it is highly recommended that the dolls be used only after specialized training and desensitization.</p

Evaluation of the consistency of neonatal skin injury assessment using clinical images and the metric and graduated colour tool

Aim: To evaluate consistency in the assessment of neonatal skin injuries. Materials and methods: Injury images collected during a multicentre period prevalence study (n = 297) were screened for optimal quality before 60 images, stratified for size and colour, were randomly selected for assessment by three neonatal and two adult specialists. The principal investigator's assessments were the baseline for comparison and consistency. Injury characteristics and assessments were reported as descriptive statistics. Comparison of injury assessments for colour and stage were calculated using Chi-square, with p-value of <0.05 considered significant. Results: Neonatal specialists assessed injury elements more confidently than adult specialists reporting 59–60 (98–100%) injuries visible compared to 51–53 (85–93%) respectively. Neonatal specialists attributed mechanical force to 93% of the skin injuries compared to 70% by adult specialists. Consistency of colour assessment was achieved more often with neonatal specialists (n = 50, 85%), compared to adult specialists (n = 41, 73%). Neonatal specialists’ consistency for injury staging (n = 107, 60%) was higher compared to adult specialists who were uncertain (n = 8,16%) and less consistent (n = 47, 44%). When comparing specialists as a group, consistency with baseline assessment was significantly different between neonatal and adult specialists for colour (p < 0.010) and injury stage (p < 0.009). Conclusion: Field of expertise (neonatal versus adult) differences were noted likely related to experience and understanding of empirical differences between neonatal and adult skin structure and maturity. These results highlight the need for specialist neonatal skin injury and wound training for clinicians involved in assessment, treatment and best practices for neonates

Frequency, location and risk factors of neonatal skin injuries from mechanical forces of pressure, friction, shear and stripping: a systematic literature review

Introduction: Recognition of neonatal skin injuries from mechanical forces and their risk factors are limited and vague. Aim: To identify frequency, locations and risk factors for neonatal skin injuries from pressure, friction, shear and/or stripping. Methods: Joanna Briggs Institute Systematic Review process was used to search and review articles from Ovid (MEDLINE), CINAHL, Scopus databases and Cochrane Library published from 1990 to 2017. Results: Of the 1545 papers originally identified, 76 full text articles were examined, 21 studies met the inclusion criteria. Studies were more likely to identify skin injuries from various etiologies (n = 7), pressure (n = 4) and stripping (n = 4). Prevalence of neonatal skin injury ranged from 9.25 to 43.1%. Risk factors included medical devices, gestational age and weight. Conclusion: Neonatal skin injuries from mechanical forces occur more frequently and differ in location from adults. Future studies need to identify modifiable risk factors and use consistent skin injury classifications applicable to neonates

Fresh Perspectives on Hospital-Acquired Neonatal Skin Injury Period Prevalence From a Multicenter Study

The objective of this study was to explore neonatal skin injury period prevalence, classification, and risk factors. Skin injury period prevalence over 9 months and χ2, Mann-Whitney U, and independent-samples t tests compared injured and noninjured neonates, with P values less than .05 considered statistically significant. Injury prediction models were developed using Classification and Regression Tree (CART) analysis for the entire cohort and separately for those classified as high or low acuity. The study took place in 3 Australian and New Zealand units. Neonates enrolled (N = 501) had a mean birth gestational age of 33.48 ± 4.61 weeks and weight of 2138.81 ± 998.92 g. Of the 501 enrolled neonates, 206 sustained skin injuries (41.1%), resulting in 391 injuries to the feet (16.4%; n = 64), cheek (12.5%; n = 49), and nose (11.3%; n = 44). Medical devices were directly associated with 61.4% (n = 240) of injuries; of these medical devices, 50.0% (n = 120) were unable to be repositioned and remained in a fixed position for treatment duration. The strongest predictor of skin injury was birth gestation of 30 weeks or less, followed by length of stay of more than 12 days, and birth weight of less than 1255 g. Prediction for injury based on illness acuity identified neonates less than 30 weeks' gestation and length of stay more than 39 days were at a greater risk (high acuity), as well as neonates less than 33 weeks' gestation and length of stay of more than 9 days (low acuity). More than 40% of hospitalized neonates acquired skin injury, of which the majority skin injuries were associated with medical devices required to sustain life. Increased neonatal clinician education and improved skin injury frameworks, informed by neonatal epidemiological data, are vital for the development of effective prevention strategies