Continuous Time Modelling Based on an Exact Discrete Time Representation

This chapter provides a survey of methods of continuous time modelling based on an exact discrete time representation. It begins by highlighting the techniques involved with the derivation of an exact discrete time representation of an underlying continuous time model,providing specificc details for a second-order linear system of stochastic differential equations. Issues of parameter identification, Granger causality, nonstationarity, and mixed frequency data are addressed, all being important considerations in applications in economics and other disciplines. Although the focus is on Gaussian estimation of the exact discrete time model, alternative time domain (state space) and frequency domain approaches are also discussed. Computational issues are explored and two new empirical applications are included along with a discussion of applications in the field of macroeconometric modelling

Frequency Domain Estimation of Continuous Time Cointegrated Models with Mixed Frequency and Mixed Sample Data

Recent work by the author on mixed frequency data analysis has focused on the estimation of cointegrated systems in continuous time based on a fully specified dynamic system of equations, while the estimation of cointegrating vectors in a discrete time system has been approached using a semiparametric frequency domain estimator. We extend the latter approach to cover the continuous time case, establishing the asymptotic properties of the frequency domain estimator and explore, in a simulation study, the effects of misspecifying the continuous time dynamic model in discrete time compared to treating the dynamics non‐parametrically. An empirical illustration is also provided

Treatment of spontaneous preterm labour with retosiban: a phase 2 proof-of-concept study

This is the peer reviewed version of the article which has been published in final form at doi: 10.1111/bcp.12646. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.AIM: To investigate the efficacy and safety of intravenous retosiban in women with spontaneous preterm labour. METHODS: Randomised, double-blind, placebo-controlled, phase 2 trial. Retosiban was administered intravenously for 48 hours to women in spontaneous preterm labour between 30(0/7) and 35(6/7)  weeks' gestation with an uncomplicated singleton pregnancy in an in-patient obstetric unit. Outcome measures were uterine quiescence (primary endpoint), days to delivery, preterm delivery, and safety. RESULTS: Uterine quiescence was achieved in 62% of women who received retosiban (n = 30) compared with 41% who received placebo (n = 34). The relative risk (RR) was 1.53 (95% credible interval [CrI]: 0.98, 2.48; NS). Retosiban resulted in a significant increase in time to delivery compared with placebo (mean difference, 8.2 days; 95% CrI: 2.7, 13.74); this difference was consistent across all gestational ages. The proportion of preterm births in the retosiban and placebo groups was 18.7% (95% CrI: 7.4%, 33.7%) and 47.2% (95% CrI: 31.4%, 63.4%), respectively. The RR of preterm birth in women treated with retosiban was 0.38 (95% CrI: 0.15, 0.81). There were no deliveries within 7 days in the retosiban group, but there were six (17.6%) births in the placebo group. Maternal, fetal, and neonatal adverse events were similar in the retosiban and placebo groups. CONCLUSIONS: Intravenous administration of retosiban in women with spontaneous preterm labour was associated with a greater than 1-week increase in time to delivery compared with placebo, a significant reduction in preterm deliveries, a non-significant increase in uterine quiescence, and a favourable safety profile.GlaxoSmithKlin

NADPH oxidases regulate septin-mediated cytoskeletal remodeling during plant infection by the rice blast fungus

notes: PMCID: PMC3581893types: Journal Article; Research Support, Non-U.S. Gov'tThe rice blast fungus Magnaporthe oryzae infects plants with a specialized cell called an appressorium, which uses turgor to drive a rigid penetration peg through the rice leaf cuticle. Here, we show that NADPH oxidases (Nox) are necessary for septin-mediated reorientation of the F-actin cytoskeleton to facilitate cuticle rupture and plant cell invasion. We report that the Nox2-NoxR complex spatially organizes a heteroligomeric septin ring at the appressorium pore, required for assembly of a toroidal F-actin network at the point of penetration peg emergence. Maintenance of the cortical F-actin network during plant infection independently requires Nox1, a second NADPH oxidase, which is necessary for penetration hypha elongation. Organization of F-actin in appressoria is disrupted by application of antioxidants, whereas latrunculin-mediated depolymerization of appressorial F-actin is competitively inhibited by reactive oxygen species, providing evidence that regulated synthesis of reactive oxygen species by fungal NADPH oxidases directly controls septin and F-actin dynamics.Biotechnology and Biological Sciences Research Council (BBSRC)National Natural Science Foundation of ChinaHalpin ScholarshipEuropean Research Council Advanced Investigator Awar

Birthplace in New South Wales, Australia: An analysis of perinatal outcomes using routinely collected data

Background: The outcomes for women who give birth in hospital compared with at home are the subject of ongoing debate. We aimed to determine whether a retrospective linked data study using routinely collected data was a viable means to compare perinatal and maternal outcomes and interventions in labour by planned place of birth at the onset of labour in one Australian state.Methods: A population-based cohort study was undertaken using routinely collected linked data from the New South Wales Perinatal Data Collection, Admitted Patient Data Collection, Register of Congenital Conditions, Registry of Birth Deaths and Marriages and the Australian Bureau of Statistics. Eight years of data provided a sample size of 258,161 full-term women and their infants. The primary outcome was a composite outcome of neonatal mortality and morbidity as used in the Birthplace in England study.Results: Women who planned to give birth in a birth centre or at home were significantly more likely to have a normal labour and birth compared with women in the labour ward group. There were no statistically significant differences in stillbirth and early neonatal deaths between the three groups, although we had insufficient statistical power to test reliably for these differences.Conclusion: This study provides information to assist the development and evaluation of different places of birth across Australia. It is feasible to examine perinatal and maternal outcomes by planned place of birth using routinely collected linked data, although very large data sets will be required to measure rare outcomes associated with place of birth in a low risk population, especially in countries like Australia where homebirth rates are low. © 2014 Homer et al.; licensee BioMed Central Ltd

FLAIR-only joint volumetric analysis of brain lesions and atrophy in clinically isolated syndrome (CIS) suggestive of multiple sclerosis

Background: MRI assessment in multiple sclerosis (MS) focuses on the presence of typical white matter (WM) lesions. Neurodegeneration characterised by brain atrophy is recognised in the research field as an important prognostic factor. It is not routinely reported clinically, in part due to difficulty in achieving reproducible measurements. Automated MRI quantification of WM lesions and brain volume could provide important clinical monitoring data. In general, lesion quantification relies on both T1 and FLAIR input images, while tissue volumetry relies on T1. However, T1-weighted scans are not routinely included in the clinical MS protocol, limiting the utility of automated quantification. Objectives: We address an aspect of this important translational challenge by assessing the performance of FLAIR-only lesion and brain segmentation, against a conventional approach requiring multi-contrast acquisition. We explore whether FLAIR-only grey matter (GM) segmentation yields more variability in performance compared with two-channel segmentation; whether this is related to field strength; and whether the results meet a level of clinical acceptability demonstrated by the ability to reproduce established biological associations. Methods: We used a multicentre dataset of subjects with a CIS suggestive of MS scanned at 1.5T and 3T in the same week. WM lesions were manually segmented by two raters, ‘manual 1′ guided by consensus reading of CIS-specific lesions and ‘manual 2′ by any WM hyperintensity. An existing brain segmentation method was adapted for FLAIR-only input. Automated segmentation of WM hyperintensity and brain volumes were performed with conventional (T1/T1 + FLAIR) and FLAIR-only methods. Results: WM lesion volumes were comparable at 1.5T between ‘manual 2′ and FLAIR-only methods and at 3T between ‘manual 2′, T1 + FLAIR and FLAIR-only methods. For cortical GM volume, linear regression measures between conventional and FLAIR-only segmentation were high (1.5T: α = 1.029, R2 = 0.997, standard error (SE) = 0.007; 3T: α = 1.019, R2 = 0.998, SE = 0.006). Age-associated change in cortical GM volume was a significant covariate in both T1 (p = 0.001) and FLAIR-only (p = 0.005) methods, confirming the expected relationship between age and GM volume for FLAIR-only segmentations. Conclusions: FLAIR-only automated segmentation of WM lesions and brain volumes were consistent with results obtained through conventional methods and had the ability to demonstrate biological effects in our study population. Imaging protocol harmonisation and validation with other MS phenotypes could facilitate the integration of automated WM lesion volume and brain atrophy analysis as clinical tools in radiological MS reporting

Maternal and perinatal outcomes by planned place of birth in Australia 2000 - 2012: A linked population data study

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Objective To compare perinatal and maternal outcomes for Australian women with uncomplicated pregnancies according to planned place of birth, that is, in hospital labour wards, birth centres or at home. Design A population-based retrospective design, linking and analysing routinely collected electronic data. Analysis comprised χ 2 tests and binary logistic regression for categorical data, yielding adjusted ORs. Continuous data were analysed using analysis of variance. Setting All eight Australian states and territories. Participants Women with uncomplicated pregnancies who gave birth between 2000 and 2012 to a singleton baby in cephalic presentation at between 37 and 41 completed weeks' gestation. Of the 1 251 420 births, 1 171 703 (93.6%) were planned in hospital labour wards, 71 505 (5.7%) in birth centres and 8212 (0.7%) at home. Main outcome measures Mode of birth, normal labour and birth, interventions and procedures during labour and birth, maternal complications, admission to special care/high dependency or intensive care units (mother or infant) and perinatal mortality (intrapartum stillbirth and neonatal death). Results Compared with planned hospital births, the odds of normal labour and birth were over twice as high in planned birth centre births (adjusted OR (AOR) 2.72; 99% CI 2.63 to 2.81) and nearly six times as high in planned home births (AOR 5.91; 99% CI 5.15 to 6.78). There were no statistically significant differences in the proportion of intrapartum stillbirths, early or late neonatal deaths between the three planned places of birth. Conclusions This is the first Australia-wide study to examine outcomes by planned place of birth. For healthy women in Australia having an uncomplicated pregnancy, planned births in birth centres or at home are associated with positive maternal outcomes although the number of homebirths was small overall. There were no significant differences in the perinatal mortality rate, although the absolute numbers of deaths were very small and therefore firm conclusions cannot be drawn about perinatal mortality outcomes

Maternal and perinatal outcomes by planned place of birth among women with low-risk pregnancies in high-income countries: A systematic review and meta-analysis

© 2018 The Author(s) Background: The comparative safety of different birth settings is widely debated. Comparing research across high-income countries is complex, given differences in maternity service provision, data discrepancies, and varying research techniques and quality. Studies of births planned at home or in birth centres have reported both better and poorer outcomes than planned hospital births. Previous systematic reviews have focused on outcomes from either birth centres or home births, with inconsistent attention to quality appraisal. Few have attempted to synthesise findings. Objective: To compare maternal and perinatal outcomes from different places of birth via a systematic review of high-quality research, and meta-analysis of appropriate data (Prospero registration CRD42016042291). Design: Reviewers searched CINAHL, Embase, Maternity and Infant Care, Medline and PsycINFO databases to identify studies comparing selected outcomes by place of birth among women with low-risk pregnancies in high-income countries. They critically appraised identified studies using an instrument specific to birth place research and then combined outcome data via meta-analysis, using RevMan software. Findings: Twenty-eight articles met inclusion criteria, yielding comparative data on perinatal mortality, mode of birth, maternal morbidity and/or NICU admissions. Meta-analysis indicated that women planning hospital births had statistically significantly lower odds of normal vaginal birth than in other planned settings. Women experienced severe perineal trauma or haemorrhage at a lower rate in planned home births than in obstetric units. There were no statistically significant differences in infant mortality by planned place of birth, although most studies had limited statistical power to detect differences for rare outcomes. Differences in location, context, quality and design of identified studies render results subject to variation. Conclusions and implications for practice: High-quality evidence about low-risk pregnancies indicates that place of birth had no statistically significant impact on infant mortality. The lower odds of maternal morbidity and obstetric intervention support the expansion of birth centre and home birth options for women with low-risk pregnancies

Patent abdominal subcutaneous veins caused by congenital absence of the inferior vena cava: a case report

<p>Abstract</p> <p>Introduction</p> <p>Patent paraumbilical and abdominal subcutaneous veins are found frequently as collaterals in patients due to portal hypertension mainly in liver cirrhosis.</p> <p>Case presentation</p> <p>For evaluation of portal hypertension in a 72-year-old Caucasian man without liver cirrhosis, magnetic resonance imaging with gadolinium contrast-enhancement was performed and demonstrated a missing inferior vena cava. A blood return from the lower extremities was shown through enlarged collateral veins of the abdominal wall, vena azygos and hemiazygos continuation, and multiple liver veins emptying into the right cardiac atrium. We describe a rare case of abdominal subcutaneous wall veins as collaterals caused by a congenitally absent infrarenal inferior vena cava with preservation of a hypoplastic suprarenal segment.</p> <p>Conclusion</p> <p>Knowledge of these congenital variations can be of clinical importance and it is imperative for the reporting radiologist to identify these anomalies as they can have a significant impact on the clinical management of the patient.</p