High-Resolution Magnetic Resonance Imaging of the Regenerating Adult Zebrafish Heart

The adult zebrafish is a well-established model for studying heart regeneration, but due to its tissue opaqueness, repair has been primarily assessed using destructive histology, precluding repeated investigations of the same animal. We present a high-resolution, non-invasive in vivo magnetic resonance imaging (MRI) method incorporating a miniature respiratory and anaesthetic perfusion set-up for live adult zebrafish, allowing for visualization of scar formation and heart regeneration in the same animal over time at an isotropic 31 µm voxel resolution. To test the method, we compared well and poorly healing cardiac ventricles using a transgenic fish model that exhibits heat-shock (HS) inducible impaired heart regeneration. HS-treated groups revealed persistent scar tissue for 10 weeks, while control groups were healed after 4 weeks. Application of the advanced MRI technique allowed clear discrimination of levels of repair following cryo- and resection injury for several months. It further provides a novel tool for in vivo time-lapse imaging of adult fish for non-cardiac studies, as the method can be readily applied to image wound healing in other injured or diseased tissues, or to monitor tissue changes over time, thus expanding the range of questions that can be addressed in adult zebrafish and other small aquatic species

Modelling the cost of place of birth: a pathway analysis

Background In New South Wales (NSW), Australia there are three settings available for women at low risk of complications to give birth: home, birth centre and hospital. Between 2000 and 2012, 93.6% of babies were planned to be born in hospital, 6.0% in a birth centre and 0.4% at home. Availability of alternative birth settings is limited and the cost of providing birth at home or in a birth centre from the perspective of the health system is unknown. Objectives The objective of this study was to model the cost of the trajectories of women who planned to give birth at home, in a birth centre or in a hospital from the public sector perspective. Methods This was a population-based study using linked datasets from NSW, Australia. Women included met the following selection criteria: 37-41 completed weeks of pregnancy, spontaneous onset of labour, and singleton pregnancy at low risk of complications. We used a decision tree framework to depict the trajectories of these women and Australian Refined-Diagnosis Related Groups (AR-DRGs) were applied to each trajectory to estimate the cost of birth. A scenario analysis was undertaken to model the cost for 30 000 women in one year. Findings 496 387 women were included in the dataset. Twelve potential outcome pathways were identified and each pathway was costed using AR-DRGs. An overall cost was also calculated by place of birth: $AUD4802 for homebirth,$AUD4979 for a birth centre birth and $AUD5463 for a hospital birth. Conclusion The findings from this study provides some clarity into the financial saving of offering more options to women seeking an alternative to giving birth in hospital. Given the relatively lower rates of complex intervention and neonatal outcomes associated with women at low risk of complications, we can assume the cost of providing them with homebirth and birth centre options could be cost-effective

Mapping the trajectories for women and their babies from births planned at home, in a birth centre or in a hospital in New South Wales, Australia, between 2000 and 2012

© 2019 The Author(s). Background: In New South Wales (NSW) Australia, women at low risk of complications can choose from three birth settings: home, birth centre and hospital. Between 2000 and 2012, around 6.4% of pregnant women planned to give birth in a birth centre (6%) or at home (0.4%) and 93.6% of women planned to birth in a hospital. A proportion of the woman in the home and birth centre groups transferred to hospital. However, their pathways or trajectories are largely unknown. Aim: The aim was to map the trajectories and interventions experienced by women and their babies from births planned at home, in a birth centre or in a hospital over a 13-year period in NSW. Methods: Using population-based linked datasets from NSW, women at low risk of complications, with singleton pregnancies, gestation 37-41 completed weeks and spontaneous onset of labour were included. We used a decision tree framework to depict the trajectories of these women and estimate the probabilities of the following: giving birth in their planned setting; being transferred; requiring interventions and neonatal admission to higher level hospital care. The trajectories were analysed by parity. Results: Over a 13-year period, 23% of nulliparous and 0.8% of multiparous women planning a home birth were transferred to hospital. In the birth centre group, 34% of nulliparae and 12% of multiparas were transferred to a hospital. Normal vaginal birth rates were higher in multiparous women compared to nulliparous women in all settings. Neonatal admission to SCN/NICU was highest in the planned hospital group for nulliparous women (10.1%), 7.1% for nulliparous women planning a birth centre birth and 5.1% of nulliparous women planning a homebirth. Multiparas had lower admissions to SCN/NICU for all thee settings (hospital 6.3%, BC 3.6%, home 1.6%, respectively). Conclusions: Women who plan to give birth at home or in a birth centre have high rates of vaginal birth, even when transferred to hospital. Evidence on the trajectories of women who choose to give birth at home or in birth centres will assist the planning, costing and expansion of models of care in NSW

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

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

Has the 'Fast-Track' referral system affected the route of presentation and/or clinical outcomes in patients with colorectal cancer?

Background: The aim of this study is to determine whether the 'Fast-Track' referral system has changed the route by which patients present with colorectal cancer (CRC) and whether the route of presentation has any effect on clinical outcome. Methods: A retrospective cohort study of patients diagnosed with CRC under the care of two consultant colorectal surgeons between April 2006 and December 2012. The route by which patients presented was categorised as Fast-Track (FT), non-Fast-Track (non-FT) or acute. Outcome variables were operative intent, disease stage and 2- and 5-year survival. Results: A total of 558 patients were identified. One hundred ninety-seven patients (35.3%) were referred as FT, 108 (19.4%) presented acutely and 253 patients (45.3%) presented via other routes (non-FT). Over the study period, the route of presentation did not change significantly (P=0.135). There was no significant difference between FT and non-FT groups in terms of the proportion of patients undergoing potentially curative surgery (70.6 vs 74.3%, P=0.092) or with node-negative disease (48.2 vs 52.2%, P=0.796) nor was there any difference in 2-year or 5-year survival (74.1 vs 73.9%, P=0.837 and 52.3 vs 53.8%, P=0.889, respectively). Patients who presented acutely were less likely to undergo curative resection, had more advanced disease and had worse 2- and 5-year survival. Conclusions: The Fast-Track referral system has not affected the route by which patients present with CRC nor has it had any effect on clinical outcomes. Alternative strategies are required if the desired improvement in outcomes is to be achieved

Celecoxib exerts protective effects in the vascular endothelium via COX-2-independent activation of AMPK-CREB-Nrf2 signalling

Although concern remains about the athero-thrombotic risk posed by cyclo-oxygenase (COX)-2-selective inhibitors, recent data implicates rofecoxib, while celecoxib appears equivalent to NSAIDs naproxen and ibuprofen. We investigated the hypothesis that celecoxib activates AMP kinase (AMPK) signalling to enhance vascular endothelial protection. In human arterial and venous endothelial cells (EC), and in contrast to ibuprofen and naproxen, celecoxib induced the protective protein heme oxygenase-1 (HO-1). Celecoxib derivative 2,5-dimethyl-celecoxib (DMC) which lacks COX-2 inhibition also upregulated HO-1, implicating a COX-2-independent mechanism. Celecoxib activated AMPKα(Thr172) and CREB-1(Ser133) phosphorylation leading to Nrf2 nuclear translocation. Importantly, these responses were not reproduced by ibuprofen or naproxen, while AMPKα silencing abrogated celecoxib-mediated CREB and Nrf2 activation. Moreover, celecoxib induced H-ferritin via the same pathway, and increased HO-1 and H-ferritin in the aortic endothelium of mice fed celecoxib (1000 ppm) or control chow. Functionally, celecoxib inhibited TNF-α-induced NF-κB p65(Ser536) phosphorylation by activating AMPK. This attenuated VCAM-1 upregulation via induction of HO-1, a response reproduced by DMC but not ibuprofen or naproxen. Similarly, celecoxib prevented IL-1β-mediated induction of IL-6. Celecoxib enhances vascular protection via AMPK-CREB-Nrf2 signalling, a mechanism which may mitigate cardiovascular risk in patients prescribed celecoxib. Understanding NSAID heterogeneity and COX-2-independent signalling will ultimately lead to safer anti-inflammatory drugs

The impact of family structure and disruption on intergenerational emotional exchange in Eastern Europe

Demographic trends across Europe involve a decrease in fertility and mortality rates, and an increase in divorce and stepfamily formation. Life courses and living arrangements have become less standardized and the structure of families has changed. In this article, we examine to what extent contemporary family structure and composition resulting from demographic changes affect emotional exchange between children and their parents, both from adult child to parent and from parent to child. Because the general level of well-being has been shown to be lower in Eastern Europe, thereby potentially affecting emotional exchange within families, we focus our research on Eastern Europe. We use the “conservation of resources theory” to derive hypotheses on how family structure may affect intergenerational emotional exchange. Family ties are assumed to be important resources of affection that people want to obtain and retain throughout their lives. Data from the Generations and Gender Survey (GGS) are used to test our hypotheses. In general, our data offer more support for the idea that families are resilient than for the often heard assumption that families are in decline as a consequence of the changed family structure and composition

Pathological and Biological Differences Between Screen-Detected and Interval Ductal Carcinoma in situ of the Breast

Background: The incidence of ductal carcinoma in situ (DCIS) has risen dramatically with the introduction of screening mammography. The aim was to evaluate differences in pathological and biological characteristics between patients with screen-detected and interval DCIS. Methods: From January 1992 to December 2001, 128 consecutive patients had been treated for pure DCIS at our institute. From these, 102 had been attending the Dutch breast cancer screening program. Sufficient paraffin-embedded tissue was available in 74 out of the 102 cases to evaluate biological marker expression (Her2/neu, ER, PR, p53 and cyclin D1) on tissue microarrays (TMA group). Differences in clinicopathological characteristics and marker expression between screen-detected and interval patients were evaluated. Screen-detected DCIS was classified as DCIS detected by screening mammography, when the two-year earlier examination failed to reveal an abnormality. Interval patients were classified as patients with DCIS detected within the two-year interval between two subsequent screening rounds. Results: Screen-detected DCIS was related with linear branching and coarse granular microcalcifications on mammography (p < .001) and with high-grade DCIS according to the Van Nuys classification (p = .025). In univariate analysis, screen-detected DCIS was related with Her2/neu overexpression (odds ratio [OR] = 6.5; 95%CI 1.3-31.0; p = .020), and interval DCIS was associated with low-grade (Van Nuys, OR = 7.3; 95% CI 1.6-33.3; p = .010) and PR positivity (OR = 0.3; 95%CI 0.1-1.0; p = .042). The multivariate analysis displayed an independent relation of Her2/neu overexpression with screen-detected DCIS (OR = 12.8; 95%CI 1.6-104.0; p = .018). Conclusions: These findings suggest that screen-detected DCIS is biologically more aggressive than interval DCIS and should not be regarded as overdiagnosis