This book contains an extensive up-to-date overview of nonlinear time series models and their application to modelling economic relationships. It considers nonlinear models in stationary and ...nonstationary frameworks, and both parametric and nonparametric models are discussed. The book contains examples of nonlinear models in economic theory and presents the most common nonlinear time series models. Importantly, it shows the reader how to apply these models in practice. For this purpose, the building of various nonlinear models with its three stages of model building: specification, estimation and evaluation, is discussed in detail and is illustrated by several examples involving both economic and non-economic data. Since estimation of nonlinear time series models is carried out using numerical algorithms, the book contains a chapter on estimating parametric nonlinear models and another on estimating nonparametric ones. Forecasting is a major reason for building time series models, linear or nonlinear. The book contains a discussion on forecasting with nonlinear models, both parametric and nonparametric, and considers numerical techniques necessary for computing multi-period forecasts from them. The main focus of the book is on models of the conditional mean, but models of the conditional variance, mainly those of autoregressive conditional heteroskedasticity, receive attention as well. A separate chapter is devoted to state space models. As a whole, the book is an indispensable tool for researchers interested in nonlinear time series and is also suitable for teaching courses in econometrics and time series analysis. Available in OSO:
Abstract Context The role of exercise intervention for patients with Non-small cell lung cancer (NSCLC) has not been systematically reviewed to date. Objective To identify, evaluate and synthesize ...the evidence examining (1) the effect of exercise intervention on exercise capacity, health related quality of life (HRQoL), physical activity levels, cancer symptoms and mortality for patients with NSCLC; and (2) the safety and feasibility of exercise intervention for a population with NSCLC. Data sources A systematic review of articles using the electronic databases MEDLINE (1950–2010), CINAHL (1982–2010), EMBASE (1980–2010), TRIP (1997–2010), Science Direct (1994–2010), PubMed (1949–2010), Cochrane Library (2010), Expanded Academic ASAP (1994–2010), Meditext Informit (1995–2010), PEDRO (1999–2010) and DARE (2010). Additional studies were identified by manually cross referencing all full text reports and personal files were searched. No publication date restrictions were imposed. Eligibility criteria for study selection Randomised controlled trials (RCTs), case–control studies and case series assessing exercise intervention to improve exercise capacity, HRQoL, level of daily physical activity, cancer symptoms or mortality of patients with NSCLC were included. Only articles available in English and published in a peer reviewed journal were included. Data extraction A data collection form was developed by one reviewer and data extracted. Data extraction was cross checked by a second reviewer. Results and data synthesis 16 studies on 13 unique patient groups totalling 675 patients with NSCLC met the inclusion criteria. The majority of studies were case series ( n = 9) and two RCTs were included. Studies exercising participants pre-operatively reported improvements in exercise capacity but no change in HRQoL immediately post exercise intervention. Studies exercising participants post-treatment (surgery, chemotherapy or radiotherapy) demonstrated improvements in exercise capacity but conflicting results with respect to the impact on HRQoL immediately post exercise intervention. Heterogeneity among studies was observed and a meta-analysis was deemed inappropriate. PRISMA guidelines were followed in reporting this systematic review. Conclusion Exercise intervention for patients with NSCLC is safe before and after cancer treatment. Interventions pre-operatively or post-cancer treatment are associated with positive benefits on exercise capacity, symptoms and some domains of HRQoL. The majority of studies are small case series therefore results should be viewed with caution until larger RCTs are completed. Further research is required to establish the effect of exercise during and after cancer treatment and in the advanced stage of disease, the optimum type of exercise training and the optimum setting for delivery.
In response to stroke, subpopulations of cortical reactive astrocytes proliferate and express proteins commonly associated with neural stem/progenitor cells such as glial fibrillary acidic protein ...(GFAP) and Nestin. To examine the stem cell-related properties of cortical reactive astrocytes after injury, we generated GFAP-CreER(TM);tdRFP mice to permanently label reactive astrocytes. We isolated cells from the cortical peri-infarct area 3 d after stroke, and cultured them in neural stem cell medium containing epidermal growth factor and basic fibroblast growth factor. We observed tdRFP-positive neural spheres in culture, suggestive of tdRFP-positive reactive astrocyte-derived neural stem/progenitor cells (Rad-NSCs). Cultured Rad-NSCs self-renewed and differentiated into neurons, astrocytes, and oligodendrocytes. Pharmacological inhibition and conditional knock-out mouse studies showed that Presenilin 1 and Notch 1 controlled neural sphere formation by Rad-NSCs after stroke. To examine the self-renewal and differentiation potential of Rad-NSCs in vivo, Rad-NSCs were transplanted into embryonic, neonatal, and adult mouse brains. Transplanted Rad-NSCs were observed to persist in the subventricular zone and secondary Rad-NSCs were isolated from the host brain 28 d after transplantation. In contrast with neurogenic postnatal day 4 NSCs and adult NSCs from the subventricular zone, transplanted Rad-NSCs differentiated into astrocytes and oligodendrocytes, but not neurons, demonstrating that Rad-NSCs had restricted differentiation in vivo. Our results indicate that Rad-NSCs are unlikely to be suitable for neuronal replacement in the absence of genetic or epigenetic modification.
Highlights • Macaques were implanted with intrathecal catheters for repeated, awake CSF sampling. • Macaques were treated with intranasal and intravenous oxytocin. • Concurrent plasma and CSF samples ...were taken at five time points after treatment. • Our results extend and partially replicate the findings of similar studies. • We highlight the importance of methodological consistency across oxytocin studies.
Assessment of atrial fibrillation (AF)-associated stroke risk is at present mainly based on clinical risk scores such as CHADS2 and CHA2DS2-VASc, although these scores provide only modest ...discrimination of risk for individual patients. Biomarkers derived from the blood may help refine risk assessment in AF for stroke outcomes and for mortality. Recent studies of biomarkers in AF have shown that they can substantially improve risk stratification. Cardiac biomarkers, such as troponin and natriuretic peptides, significantly improve risk stratification in addition to current clinical risk stratification models. Similar findings have recently been described for markers of renal function, coagulation, and inflammation in AF populations based on large randomized prospective clinical trials or large community-based cohorts. These new findings may enable development of novel tools to improve clinical risk assessment in AF. Biomarkers in AF may also improve the understanding of the pathophysiology of AF further as well as potentially elucidate novel treatment targets. This review will highlight novel associations of biomarkers and outcomes in AF as well as recent progress in the use of biomarkers for risk stratification.
In these three essays, Professor Granger explains the process of constructing and evaluating an empirical model. Drawing on a wide range of cases and vignettes from economics, finance, politics and ...environment economics, as well as from art, literature, and the entertainment industry, Professor Granger combines rigour with intuition to provide a unique and entertaining insight into one of the most important subjects in modern economics. Chapter 1 deals with Specification. The process of specifying a model is discussed using deforestation in the Amazon region of Brazil as an illustration. Chapter 2 considers Evaluation, and argues that insufficent evaluation is undertaken by economists, and that models should be evaluated in terms of the quality of their output. In Chapter 3, the question of how to evaluate forecasts is considered at several levels of increasing depth and using a more sophisticated, technical approach than in the earlier two chapters.
Purpose
The aims of this study are to investigate the feasibility of an exercise program commencing 60 days following allogeneic stem cell transplantation (alloSCT), to investigate changes in ...physical function and health-related quality of life (HRQoL) in patients from pre- to post-alloSCT and to explore changes in patient outcomes before and after the program.
Methods
This study is a single site, prospective case series including 43 adults undergoing alloSCT. The intervention was an 8-week outpatient and home-based exercise and education program. Outcomes included feasibility (consent, attendance, compliance and completion rates), functional exercise capacity (incremental shuttle walk test), muscle strength (hand-held dynamometry), self-efficacy for physical activity (Physical Activity Assessment Inventory) and HRQoL (Functional Assessment of Cancer Therapy-Bone Marrow Transplant). Outcomes were measured pre-alloSCT, 60 days post-alloSCT (pre-intervention) and 100 days post-alloSCT (post-intervention).
Results
The consent rate was 93%. From baseline to 60 days post-alloSCT, there was significant decline in functional exercise capacity (mean difference 224 m, 95% CI 153–295,
p
< 0.0005), self-efficacy for physical activity (294 points, 95% CI 136–452,
p
= 0.001) and HRQoL (15 points, 95% CI 8–21,
p
< 0.0005). Ten participants did not commence the exercise program due to death (
n
= 5), illness (
n
= 1) or cancellation of alloSCT (
n
= 4). The intervention was feasible in those not affected by major medical complications or death. No adverse events occurred. From pre- to post-intervention, there was significant improvement in functional exercise capacity (
p
= 0.001) and HRQoL (
p
= 0.001).
Conclusions
AlloSCT results in significant decline in functional exercise capacity, self-efficacy for physical activity and HRQoL, which may be improved through an exercise program. This pilot demonstrated safety, feasibility and high patient interest. Further randomised research is required.
Aims
We tested the hypothesis that candesartan improves outcomes in heart failure (HF) with mid‐range ejection fraction HFmrEF; ejection fraction (EF) 40–49%.
Methods and results
In 7598 patients ...enrolled in the CHARM Programme (HF across the spectrum of EF), we assessed characteristics, outcomes and treatment effect of candesartan according to EF. Patients with HFmrEF (n = 1322, 17%) were similar to those with HF with reduced EF (HFrEF; n = 4323, 57%) with respect to some characteristics, and intermediate between HFrEF and HF with preserved EF (HFpEF; n = 1953, 26%) with respect to others. Over a mean follow‐up of 2.9 years, the incidence rates for the primary outcome of cardiovascular death or HF hospitalization were 15.9, 8.5 and 8.9 per 100 patient‐years in HFrEF, HFmrEF and HFpEF. In adjusted analyses, the rates of the primary outcome declined with increasing EF up to 50%. For treatment effect, the incidence rates for the primary outcome for candesartan vs. placebo were 14.4 vs. 17.5 per 100 patient‐years in HFrEF hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.75–0.91; P < 0.001, 7.4 vs. 9.7 per 100 patient‐years in HFmrEF (HR 0.76, 95% CI 0.61–0.96; P = 0.02), and 8.6 vs. 9.1 per 100 patient‐years in HFpEF (HR 0.95, 95% CI 0.79–1.14; P = 0.57). For recurrent HF hospitalization, the incidence rate ratios were 0.68 in HFrEF (95% CI 0.58–0.80; P < 0.001), 0.48 in HFmrEF (95% CI 0.33–0.70; P < 0.001), and 0.78 in HFpEF (95% CI 0.59–1.03; P = 0.08). With EF as a continuous spline variable, candesartan significantly reduced the primary outcome until EF well over 50% and recurrent HF hospitalizations until EF well over 60%.
Conclusion
Candesartan improved outcomes in HFmrEF to a similar degree as in HFrEF.
ClinicalTrials.gov: CHARM Alternative NCT00634400, CHARM Added NCT00634309, CHARM Preserved NCT00634712
The combination of a single-bolus fibrinolytic and a low-molecular-weight heparin may facilitate prehospital reperfusion and further improve clinical outcome in patients with ST-elevation myocardial ...infarction.
In the prehospital setting, 1639 patients with ST-elevation myocardial infarction were randomly assigned to treatment with tenecteplase and either (1) intravenous bolus of 30 mg enoxaparin (ENOX) followed by 1 mg/kg subcutaneously BID for a maximum of 7 days or (2) weight-adjusted unfractionated heparin (UFH) for 48 hours. The median treatment delay was 115 minutes after symptom onset (53% within 2 hours). ENOX tended to reduce the composite of 30-day mortality or in-hospital reinfarction, or in-hospital refractory ischemia to 14.2% versus 17.4% for UFH (P=0.080), although there was no difference for this composite end point plus in-hospital intracranial hemorrhage or major bleeding (18.3% versus 20.3%, P=0.30). Correspondingly, there were reductions in in-hospital reinfarction (3.5% versus 5.8%, P=0.028) and refractory ischemia (4.4% versus 6.5%, P=0.067) but increases in total stroke (2.9% versus 1.3%, P=0.026) and intracranial hemorrhage (2.20% versus 0.97%, P=0.047). The increase in intracranial hemorrhage was seen in patients >75 years of age.
Prehospital fibrinolysis allows 53% of patients to receive reperfusion treatment within 2 hours after symptom onset. The combination of tenecteplase with ENOX reduces early ischemic events, but lower doses of ENOX need to be tested in elderly patients. At present, therefore, tenecteplase and UFH are recommended as the routine pharmacological reperfusion treatment in the prehospital setting.
PDF
