1,692 research outputs found

    Cloud adjustment and its role in CO 2 radiative forcing and climate sensitivity: a review

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    Understanding the role of clouds in climate change remains a considerable challenge. Traditionally, this challenge has been framed in terms of understanding cloud feedback. However, recent work suggests that under increasing levels of atmospheric carbon dioxide, clouds not only amplify or dampen climate change through global feedback processes, but also through rapid (days to weeks) tropospheric temperature and land surface adjustments. In this article, we use the Met Office Hadley Centre climate model HadGSM1 to review these recent developments and assess their impact on radiative forcing and equilibrium climate sensitivity. We estimate that cloud adjustment contributes ~0.8 K to the 4.4 K equilibrium climate sensitivity of this particular model. We discuss the methods used to evaluate cloud adjustments, highlight the mechanisms and processes involved and identify low level cloudiness as a key cloud type. Looking forward, we discuss the outstanding issues, such as the application to transient forcing scenarios. We suggest that the upcoming CMIP5 multi-model database will allow a comprehensive assessment of the significance of cloud adjustments in fully coupled atmosphere-ocean-general-circulation models for the first time, and that future research should exploit this opportunity to understand cloud adjustments/feedbacks in non-idealised transient climate change scenarios

    Evidence of a metabolic memory to early-life dietary restriction in male C57BL/6 mice

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    <p>Background: Dietary restriction (DR) extends lifespan and induces beneficial metabolic effects in many animals. What is far less clear is whether animals retain a metabolic memory to previous DR exposure, that is, can early-life DR preserve beneficial metabolic effects later in life even after the resumption of ad libitum (AL) feeding. We examined a range of metabolic parameters (body mass, body composition (lean and fat mass), glucose tolerance, fed blood glucose, fasting plasma insulin and insulin-like growth factor 1 (IGF-1), insulin sensitivity) in male C57BL/6 mice dietary switched from DR to AL (DR-AL) at 11 months of age (mid life). The converse switch (AL-DR) was also undertaken at this time. We then compared metabolic parameters of the switched mice to one another and to age-matched mice maintained exclusively on an AL or DR diet from early life (3 months of age) at 1 month, 6 months or 10 months post switch.</p> <p>Results: Male mice dietary switched from AL-DR in mid life adopted the metabolic phenotype of mice exposed to DR from early life, so by the 10-month timepoint the AL-DR mice overlapped significantly with the DR mice in terms of their metabolic phenotype. Those animals switched from DR-AL in mid life showed clear evidence of a glycemic memory, with significantly improved glucose tolerance relative to mice maintained exclusively on AL feeding from early life. This difference in glucose tolerance was still apparent 10 months after the dietary switch, despite body mass, fasting insulin levels and insulin sensitivity all being similar to AL mice at this time.</p> <p>Conclusions: Male C57BL/6 mice retain a long-term glycemic memory of early-life DR, in that glucose tolerance is enhanced in mice switched from DR-AL in mid life, relative to AL mice, even 10 months following the dietary switch. These data therefore indicate that the phenotypic benefits of DR are not completely dissipated following a return to AL feeding. The challenge now is to understand the molecular mechanisms underlying these effects, the time course of these effects and whether similar interventions can confer comparable benefits in humans.</p&gt

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

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    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

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    © 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

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    © 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

    A Phase I study of the safety, pharmacokinetics and efficacy of navitoclax plus docetaxel in patients with advanced solid tumors

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    Aim: This Phase I study investigated safety of navitoclax and docetaxel in patients (n = 41) with advanced solid tumors. Patients & methods: Two navitoclax plus docetaxel dosing schedules (21 and 28 days) were evaluated. Maximum tolerated dose, dose-limiting toxicities and preliminary antitumor activity were assessed. Results: Ten (24%) patients experienced dose-limiting toxicities; dose-escalation cohorts: n = 7 (21-day schedule: n = 5; 28-day schedule: n = 2) and 21-day expanded safety cohort: n = 3. Navitoclax 150-mg days 1-5 every 21 days with docetaxel 75 mg/m2 day 1 was the maximum tolerated dose and optimal schedule. Adverse events included thrombocytopenia (63%), fatigue (61%), nausea (59%) and neutropenia (51%). Four confirmed partial responses occurred. Conclusion: Navitoclax 150-mg orally once/day was safely administered with docetaxel. Myelosuppression limited dose escalation; antitumor activity was observed. Clinical trial registration: NCT00888108 (ClinicalTrials.gov)

    Does adding risk-trends to survival models improve in-hospital mortality predictions? A cohort study

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    <p>Abstract</p> <p>Background</p> <p>Clinicians informally assess changes in patients' status over time to prognosticate their outcomes. The incorporation of trends in patient status into regression models could improve their ability to predict outcomes. In this study, we used a unique approach to measure trends in patient hospital death risk and determined whether the incorporation of these trend measures into a survival model improved the accuracy of its risk predictions.</p> <p>Methods</p> <p>We included all adult inpatient hospitalizations between 1 April 2004 and 31 March 2009 at our institution. We used the daily mortality risk scores from an existing time-dependent survival model to create five trend indicators: absolute and relative percent change in the risk score from the previous day; absolute and relative percent change in the risk score from the start of the trend; and number of days with a trend in the risk score. In the derivation set, we determined which trend indicators were associated with time to death in hospital, independent of the existing covariates. In the validation set, we compared the predictive performance of the existing model with and without the trend indicators.</p> <p>Results</p> <p>Three trend indicators were independently associated with time to hospital mortality: the absolute change in the risk score from the previous day; the absolute change in the risk score from the start of the trend; and the number of consecutive days with a trend in the risk score. However, adding these trend indicators to the existing model resulted in only small improvements in model discrimination and calibration.</p> <p>Conclusions</p> <p>We produced several indicators of trend in patient risk that were significantly associated with time to hospital death independent of the model used to create them. In other survival models, our approach of incorporating risk trends could be explored to improve their performance without the collection of additional data.</p

    A qualitative study of professional and carer perceptions of the threats to safe hospital discharge for stroke and hip fracture patients in the English National Health Service

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    Background: Hospital discharge is a vulnerable transitional stage in patient care. This qualitative study investigated the views of healthcare professionals and patients about the threats to safe hospital discharge with aim of identifying contributory and latent factors. The study was undertaken in two regional health and social care systems in the English National Health Service, each comprising three acute hospitals, community and primary care providers and municipal social care services. The study focused on the threats to safe discharge for hip fracture and stroke patients as exemplars of complex care transitions. Methods: A qualitative study involving narrative interviews with 213 representative stakeholders and professionals involved in discharge planning and care transition activities. Narratives were analysed in line with ‘systems’ thinking to identify proximal (active) and distal (latent) factors, and the relationships between them. Results: Three linked categories of commonly and consistently identified threat to safe discharge were identified:(1) ‘direct’ patient harms comprising falls, infection, sores and ulceration, medicines-related issues, and relapse; (2) proximal ‘contributing’ factors including completion of tests, assessment of patient, management of equipment and medicines, care plan, follow-up care and patient education; and distal ‘latent’ factors including discharge planning, referral processes, discharge timing, resources constraints, and organisational demands. Conclusion: From the perspective of stakeholders, the study elaborates the relationship between patient harms and systemic factors in the context of hospital discharge. It supports the importance of communication and collaboration across occupational and organisational boundaries, but also the challenges to supporting such communication with the inherent complexity of the care system
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