One-Step Recurrences for Stationary Random Fields on the Sphere

Recurrences for positive definite functions in terms of the space dimension have been used in several fields of applications. Such recurrences typically relate to properties of the system of special functions characterizing the geometry of the underlying space. In the case of the sphere ${\mathbb S}^{d-1} \subset {\mathbb R}^d$ the (strict) positive definiteness of the zonal function $f(\cos \theta)$ is determined by the signs of the coefficients in the expansion of $f$ in terms of the Gegenbauer polynomials $\{C^\lambda_n\}$, with $\lambda=(d-2)/2$. Recent results show that classical differentiation and integration applied to $f$ have positive definiteness preserving properties in this context. However, in these results the space dimension changes in steps of two. This paper develops operators for zonal functions on the sphere which preserve (strict) positive definiteness while moving up and down in the ladder of dimensions by steps of one. These fractional operators are constructed to act appropriately on the Gegenbauer polynomials $\{C^\lambda_n\}$

Localized bases for kernel spaces on the unit sphere

Approximation/interpolation from spaces of positive definite or conditionally positive definite kernels is an increasingly popular tool for the analysis and synthesis of scattered data, and is central to many meshless methods. For a set of $N$ scattered sites, the standard basis for such a space utilizes $N$ \emph{globally} supported kernels; computing with it is prohibitively expensive for large $N$. Easily computable, well-localized bases, with "small-footprint" basis elements - i.e., elements using only a small number of kernels -- have been unavailable. Working on \sphere, with focus on the restricted surface spline kernels (e.g. the thin-plate splines restricted to the sphere), we construct easily computable, spatially well-localized, small-footprint, robust bases for the associated kernel spaces. Our theory predicts that each element of the local basis is constructed by using a combination of only $\mathcal{O}((\log N)^2)$ kernels, which makes the construction computationally cheap. We prove that the new basis is $L_p$ stable and satisfies polynomial decay estimates that are stationary with respect to the density of the data sites, and we present a quasi-interpolation scheme that provides optimal $L_p$ approximation orders. Although our focus is on $\mathbb{S}^2$, much of the theory applies to other manifolds - $\mathbb{S}^d$, the rotation group, and so on. Finally, we construct algorithms to implement these schemes and use them to conduct numerical experiments, which validate our theory for interpolation problems on $\mathbb{S}^2$ involving over one hundred fifty thousand data sites.Comment: This article supersedes arXiv:1111.1013 "Better bases for kernel spaces," which proved existence of better bases for various kernel spaces. This article treats a smaller class of kernels, but presents an algorithm for constructing better bases and demonstrates its effectiveness with more elaborate examples. A quasi-interpolation scheme is introduced that provides optimal linear convergence rate

Performance of externally validated enhanced computer-aided versions of the National Early Warning Score in predicting mortality following an emergency admission to hospital in England: a cross-sectional study

YesOBJECTIVES: In the English National Health Service, the patient's vital signs are monitored and summarised into a National Early Warning Score (NEWS) to support clinical decision making, but it does not provide an estimate of the patient's risk of death. We examine the extent to which the accuracy of NEWS for predicting mortality could be improved by enhanced computer versions of NEWS (cNEWS). DESIGN: Logistic regression model development and external validation study. SETTING: Two acute hospitals (YH-York Hospital for model development; NH-Northern Lincolnshire and Goole Hospital for external model validation). PARTICIPANTS: Adult (≥16 years) medical admissions discharged over a 24-month period with electronic NEWS (eNEWS) recorded on admission are used to predict mortality at four time points (in-hospital, 24 hours, 48 hours and 72 hours) using the first electronically recorded NEWS (model M0) versus a cNEWS model which included age+sex (model M1) +subcomponents of NEWS (including diastolic blood pressure) (model M2). RESULTS: The risk of dying in-hospital following emergency medical admission was 5.8% (YH: 2080/35 807) and 5.4% (NH: 1900/35 161). The c-statistics for model M2 in YH for predicting mortality (in-hospital=0.82, 24 hours=0.91, 48 hours=0.88 and 72 hours=0.88) was higher than model M0 (in-hospital=0.74, 24 hours=0.89, 48 hours=0.86 and 72 hours=0.85) with higher Positive Predictive Value (PPVs) for in-hospital mortality (M2 19.3% and M0 16.6%). Similar findings were seen in NH. Model M2 performed better than M0 in almost all major disease subgroups. CONCLUSIONS: An externally validated enhanced computer-aided NEWS model (cNEWS) incrementally improves on the performance of a NEWS only model. Since cNEWS places no additional data collection burden on clinicians and is readily automated, it may now be carefully introduced and evaluated to determine if it can improve care in hospitals that have eNEWS systems.This research was supported by the Health Foundation. The Health Foundation is an independent charity working to improve the quality of healthcare in the UK. This research was also supported by the National Institute for Health Research (NIHR) Yorkshire and Humberside Patient Safety Translational Research Centre (YHPSTRC)

The inclusion of delirium in version 2 of the National Early Warning Score will substantially increase the alerts for escalating levels of care: findings from a retrospective database study of emergency medical admissions in two hospitals

YesBackground The National Early Warning Score (NEWS) is being replaced with NEWS2 which adds 3 points for new confusion or delirium. We estimated the impact of adding delirium on the number of medium/high level alerts that are triggers to escalate care. Methods Analysis of emergency medical admissions in two acute hospitals (York Hospital (YH) and Northern Lincolnshire and Goole NHS Foundation Trust hospitals (NH)) in England. Twenty per cent were randomly assigned to have delirium. Results The number of emergency admissions (YH: 35584; NH: 35795), mortality (YH: 5.7%; NH: 5.5%), index NEWS (YH: 2.5; NH: 2.1) and numbers of NEWS recorded (YH: 879193; NH: 884072) were similar in each hospital. The mean number of patients with medium level alerts per day increased from 55.3 (NEWS) to 69.5 (NEWS2), a 25.7% increase in YH and 64.1 (NEWS) to 77.4 (NEWS2), a 20.7% increase in NH. The mean number of patients with high level alerts per day increased from 27.3 (NEWS) to 34.4 (NEWS2), a 26.0% increase in YH and 29.9 (NEWS) to 37.7 (NEWS2), a 26.1% increase in NH. Conclusions The addition of delirium in NEWS2 will have a substantial increase in medium and high level alerts in hospitalised emergency medical patients. Rigorous evaluation of NEWS2 is required before widespread implementation because the extent to which staff can cope with this increase without adverse consequences remains unknown

Computer-aided National Early Warning Score to predict the risk of sepsis following emergency medical admission to hospital: a model development and external validation study

YesBackground: In English hospitals, the patient’s vital signs are monitored and summarised into a National Early Warning Score (NEWS). NEWS is more accurate than the quick sepsis related organ failure assessment (qSOFA) score at identifying patients with sepsis. We investigate the extent to which the accuracy of the NEWS is enhanced by developing computer-aided NEWS (cNEWS) models. We compared three cNEWS models (M0=NEWS alone; M1=M0 + age + sex; M2=M1 + subcomponents of NEWS + diastolic blood pressure) to predict the risk of sepsis. Methods: All adult emergency medical admissions discharged over 24-months from two acute hospitals (YH–York Hospital for model development; NH–Northern Lincolnshire and Goole Hospital for external model validation). We used a validated Canadian method for defining sepsis from administrative hospital data. Findings: The prevalence of sepsis was lower in YH (4.5%=1596/35807) than NH (8.5%=2983/35161). The c-statistic increased across models (YH: M0: 0.705, M1:0.763, M2:0.777; NH:M0: 0.708, M1:0.777, M2:0.791). At NEWS 5+, sensitivity increased (YH: 47.24% vs 50.56% vs 52.69%; NH: 37.91% vs 43.35% vs 48.07%)., the positive likelihood ratio increased (YH: 2.77 vs 2.99 vs 3.06; NH: 3.18 vs 3.32 vs 3.45) and the positive predictive value increased (YH: 11.44% vs 12.24% vs 12.49%; NH: 22.75% vs 23.55% vs 24.21%). Interpretation: From the three cNEWS models, Model M2 is the most accurate. Since it places no additional data collection burden on clinicians and can be automated, it may now be carefully introduced and evaluated in hospitals with sufficient informatics infrastructure.The Health Foundation, National Institute for Health Research (NIHR) Yorkshire and Humberside Patient Safety Translational Research CentreResearch Development Fund Publication Prize Award winner, April 2019

Legionella pneumophila strain 130b possesses a unique combination of type IV secretion systems and novel Dot/Icm secretion system effector proteins

Legionella pneumophila is a ubiquitous inhabitant of environmental water reservoirs. The bacteria infect a wide variety of protozoa and, after accidental inhalation, human alveolar macrophages, which can lead to severe pneumonia. The capability to thrive in phagocytic hosts is dependent on the Dot/Icm type IV secretion system (T4SS), which translocates multiple effector proteins into the host cell. In this study, we determined the draft genome sequence of L. pneumophila strain 130b (Wadsworth). We found that the 130b genome encodes a unique set of T4SSs, namely, the Dot/Icm T4SS, a Trb-1-like T4SS, and two Lvh T4SS gene clusters. Sequence analysis substantiated that a core set of 107 Dot/Icm T4SS effectors was conserved among the sequenced L. pneumophila strains Philadelphia-1, Lens, Paris, Corby, Alcoy, and 130b. We also identified new effector candidates and validated the translocation of 10 novel Dot/Icm T4SS effectors that are not present in L. pneumophila strain Philadelphia-1. We examined the prevalence of the new effector genes among 87 environmental and clinical L. pneumophila isolates. Five of the new effectors were identified in 34 to 62% of the isolates, while less than 15% of the strains tested positive for the other five genes. Collectively, our data show that the core set of conserved Dot/Icm T4SS effector proteins is supplemented by a variable repertoire of accessory effectors that may partly account for differences in the virulences and prevalences of particular L. pneumophila strains. Copyright © 2010, American Society for Microbiology. All Rights Reserved

HER2 mediates PSMA/mGluR1-driven resistance to the DS-7423 dual PI3K/mTOR inhibitor in PTEN wild-type prostate cancer models

Prostate cancer remains a major cause of male mortality. Genetic alteration of the PI3K/AKT/mTOR pathway is one of the key events in tumor development and progression in prostate cancer, with inactivation of the PTEN tumor suppressor being very common in this cancer type. Extensive evaluation has been performed on the therapeutic potential of PI3K/AKT/mTOR inhibitors and the resistance mechanisms arising in patients with PTEN-mutant background. However, in patients with a PTEN wild-type phenotype, PI3K/AKT/mTOR inhibitors have not demonstrated efficacy, and this remains an area of clinical unmet need. In this study, we have investigated the response of PTEN wild-type prostate cancer cell lines to the dual PI3K/mTOR inhibitor DS-7423 alone or in combination with HER2 inhibitors or mGluR1 inhibitors. Upon treatment with the dual PI3K/mTOR inhibitor DS-7423, PTEN wild-type prostate cancer CWR22/22RV1 cells upregulate expression of the proteins PSMA, mGluR1, and the tyrosine kinase receptor HER2, while PTEN-mutant LNCaP cells upregulate androgen receptor and HER3. PSMA, mGluR1, and HER2 exert control over one another in a positive feedback loop that allows cells to overcome treatment with DS-7423. Concomitant targeting of PI3K/mTOR with either HER2 or mGluR1 inhibitors results in decreased cell survival and tumor growth in xenograft studies. Our results suggest a novel therapeutic possibility for patients with PTEN wild-type PI3K/AKT-mutant prostate cancer based in the combination of PI3K/mTOR blockade with HER2 or mGluR1 inhibitors

Mechanisms involved in acquisition of blaNDM genes by IncA/C2 and IncFIIY plasmids

blaNDM genes confer carbapenem resistance and have been identified on transferable plasmids belonging to different incompatibility (Inc) groups. Here we present the complete sequences of four plasmids carrying a blaNDM gene, pKP1-NDM-1, pEC2-NDM-3, pECL3-NDM-1, and pEC4-NDM-6, from four clinical samples originating from four different patients. Different plasmids carry segments that align to different parts of the blaNDM region found on Acinetobacter plasmids. pKP1-NDM-1 and pEC2-NDM-3, from Klebsiella pneumoniae and Escherichia coli, respectively, were identified as type 1 IncA/C2 plasmids with almost identical backbones. Different regions carrying blaNDM are inserted in different locations in the antibiotic resistance island known as ARI-A, and ISCR1 may have been involved in the acquisition of blaNDM-3 by pEC2-NDM-3. pECL3-NDM-1 and pEC4-NDM-6, from Enterobacter cloacae and E. coli, respectively, have similar IncFIIY backbones, but different regions carrying blaNDM are found in different locations. Tn3-derived inverted-repeat transposable elements (TIME) appear to have been involved in the acquisition of blaNDM-6 by pEC4-NDM-6 and the rmtC 16S rRNA methylase gene by IncFIIY plasmids. Characterization of these plasmids further demonstrates that even very closely related plasmids may have acquired blaNDM genes by different mechanisms. These findings also illustrate the complex relationships between antimicrobial resistance genes, transposable elements, and plasmids and provide insights into the possible routes for transmission of blaNDM genes among species of the Enterobacteriaceae family