Preoperative aerobic fitness and perioperative outcomes in patients undergoing cystectomy before and after implementation of a national lockdown

Abstract Background Lower fitness is a predictor of adverse outcomes after radical cystectomy. Lockdown measures during the COVID-19 pandemic affected daily physical activity. We hypothesised that lockdown during the pandemic was associated with a reduction in preoperative aerobic fitness and an increase in postoperative complications in patients undergoing radical cystectomy. Methods We reviewed routine preoperative cardiopulmonary exercise testing (CPET) data collected prior to the pandemic (September 2018 to March 2020) and after lockdown (March 2020 to July 2021) in patients undergoing radical cystectomy. Differences in CPET variables, Postoperative Morbidity Survey (POMS) data, and length of hospital stay were compared. Results We identified 267 patients (85 pre-lockdown and 83 during lockdown) who underwent CPET and radical cystectomy. Patients undergoing radical cystectomy throughout lockdown had lower ventilatory anaerobic threshold (9.0 [7.9–10.9] vs 10.3 [9.1–12.3] ml kg−1 min−1; P=0.0002), peak oxygen uptake (15.5 [12.9–19.1] vs 17.5 [14.4–21.0] ml kg−1 min−1; P=0.015), and higher ventilatory equivalents for carbon dioxide (34.7 [31.4–38.5] vs 33.4 [30.5–36.5]; P=0.030) compared with pre-lockdown. Changes were more pronounced in males and those aged >65 yr. Patients undergoing radical cystectomy throughout lockdown had a higher proportion of day 5 POMS-defined morbidity (89% vs 75%, odds ratio [OR] 2.698, 95% confidence interval [CI] 1.143–6.653; P=0.019), specifically related to pulmonary complications (30% vs 13%, OR 2.900, 95% CI 1.368–6.194; P=0.007) and pain (27% vs 9%, OR 3.471, 95% CI 1.427–7.960; P=0.004), compared with pre-lockdown on univariate analysis. Conclusions Lockdown measures in response to the COVID-19 pandemic were associated with a reduction in fitness and an increase in postoperative morbidity among patients undergoing radical cystectomy

Entropy production and coarse graining of the climate fields in a general circulation model

We extend the analysis of the thermodynamics of the climate system by investigating the role played by processes taking place at various spatial and temporal scales through a procedure of coarse graining. We show that the coarser is the graining of the climatic fields, the lower is the resulting estimate of the material entropy production. In other terms, all the spatial and temporal scales of variability of the thermodynamic fields provide a positive contribution to the material entropy production. This may be interpreted also as that, at all scales, the temperature fields and the heating fields resulting from the convergence of turbulent fluxes have a negative correlation, while the opposite holds between the temperature fields and the radiative heating fields. Moreover, we obtain that the latter correlations are stronger, which confirms that radiation acts as primary driver for the climatic processes, while the material fluxes dampen the resulting fluctuations through dissipative processes. We also show, using specific coarse-graining procedures, how one can separate the various contributions to the material entropy production coming from the dissipation of kinetic energy, the vertical sensible and latent heat fluxes, and the large scale horizontal fluxes, without resorting to the full three-dimensional time dependent fields. We find that most of the entropy production is associated to irreversible exchanges occurring along the vertical direction, and that neglecting the horizontal and time variability of the fields has a relatively small impact on the estimate of the material entropy production. The approach presented here seems promising for testing climate models, for assessing the impact of changing their parametrizations and their resolution, as well as for investigating the atmosphere of exoplanets, because it allows for evaluating the error in the estimate of their thermodynamical properties due to the lack of high-resolution data. The findings on the impact of coarse graining on the thermodynamic fields on the estimate of the material entropy production deserve to be explored in a more general context, because they provide a way for understanding the relationship between forced fluctuations and dissipative processes in continuum systems

Fostering implementation of health services research findings into practice: a consolidated framework for advancing implementation science

Abstract Background Many interventions found to be effective in health services research studies fail to translate into meaningful patient care outcomes across multiple contexts. Health services researchers recognize the need to evaluate not only summative outcomes but also formative outcomes to assess the extent to which implementation is effective in a specific setting, prolongs sustainability, and promotes dissemination into other settings. Many implementation theories have been published to help promote effective implementation. However, they overlap considerably in the constructs included in individual theories, and a comparison of theories reveals that each is missing important constructs included in other theories. In addition, terminology and definitions are not consistent across theories. We describe the Consolidated Framework For Implementation Research (CFIR) that offers an overarching typology to promote implementation theory development and verification about what works where and why across multiple contexts. Methods We used a snowball sampling approach to identify published theories that were evaluated to identify constructs based on strength of conceptual or empirical support for influence on implementation, consistency in definitions, alignment with our own findings, and potential for measurement. We combined constructs across published theories that had different labels but were redundant or overlapping in definition, and we parsed apart constructs that conflated underlying concepts. Results The CFIR is composed of five major domains: intervention characteristics, outer setting, inner setting, characteristics of the individuals involved, and the process of implementation. Eight constructs were identified related to the intervention (e.g., evidence strength and quality), four constructs were identified related to outer setting (e.g., patient needs and resources), 12 constructs were identified related to inner setting (e.g., culture, leadership engagement), five constructs were identified related to individual characteristics, and eight constructs were identified related to process (e.g., plan, evaluate, and reflect). We present explicit definitions for each construct. Conclusion The CFIR provides a pragmatic structure for approaching complex, interacting, multi-level, and transient states of constructs in the real world by embracing, consolidating, and unifying key constructs from published implementation theories. It can be used to guide formative evaluations and build the implementation knowledge base across multiple studies and settings.http://deepblue.lib.umich.edu/bitstream/2027.42/78272/1/1748-5908-4-50.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/2/1748-5908-4-50-S1.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/3/1748-5908-4-50-S3.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/4/1748-5908-4-50-S4.PDFhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/5/1748-5908-4-50.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/78272/6/1748-5908-4-50-S2.PDFPeer Reviewe

Combining Computational Prediction of Cis-Regulatory Elements with a New Enhancer Assay to Efficiently Label Neuronal Structures in the Medaka Fish

The developing vertebrate nervous system contains a remarkable array of neural cells organized into complex, evolutionarily conserved structures. The labeling of living cells in these structures is key for the understanding of brain development and function, yet the generation of stable lines expressing reporter genes in specific spatio-temporal patterns remains a limiting step. In this study we present a fast and reliable pipeline to efficiently generate a set of stable lines expressing a reporter gene in multiple neuronal structures in the developing nervous system in medaka. The pipeline combines both the accurate computational genome-wide prediction of neuronal specific cis-regulatory modules (CRMs) and a newly developed experimental setup to rapidly obtain transgenic lines in a cost-effective and highly reproducible manner. 95% of the CRMs tested in our experimental setup show enhancer activity in various and numerous neuronal structures belonging to all major brain subdivisions. This pipeline represents a significant step towards the dissection of embryonic neuronal development in vertebrates

Transplantation of Neuronal-Primed Human Bone Marrow Mesenchymal Stem Cells in Hemiparkinsonian Rodents

Bone marrow-derived human mesenchymal stem cells (hMSCs) have shown promise in in vitro neuronal differentiation and in cellular therapy for neurodegenerative disorders, including Parkinson' disease. However, the effects of intracerebral transplantation are not well defined, and studies do not agreed on the optimal neuronal differentiation method. Here, we investigated three growth factor-based neuronal differentiation procedures (using FGF-2/EGF/PDGF/SHH/FGF-8/GDNF), and found all to be capable of eliciting an immature neural phenotype, in terms of cell morphology and gene/protein expression. The neuronal-priming (FGF-2/EGF) method induced neurosphere-like formation and the highest NES and NR4A2 expression by hMSCs. Transplantation of undifferentiated and neuronal-primed hMSCs into the striatum and substantia nigra of 6-OHDA-lesioned hemiparkinsonian rats revealed transient graft survival of 7 days, despite the reported immunosuppressive properties of MSCs and cyclosporine-immunosuppression of rats. Neither differentiation of hMSCs nor induction of host neurogenesis was observed at injection sites, and hMSCs continued producing mesodermal fibronectin. Strategies for improving engraftment and differentiation post-transplantation, such as prior in vitro neuronal-priming, nigral and striatal grafting, and co-transplantation of olfactory ensheathing cells that promote neural regeneration, were unable to provide advantages. Innate inflammatory responses (Iba-1-positive microglia/macrophage and GFAP-positive astrocyte activation and accumulation) were detected around grafts within 7 days. Our findings indicate that growth factor-based methods allow hMSC differentiation toward immature neuronal-like cells, and contrary to previous reports, only transient survival and engraftment of hMSCs occurs following transplantation in immunosuppressed hemiparkinsonian rats. In addition, suppression of host innate inflammatory responses may be a key factor for improving hMSC survival and engraftment

Worldwide comparison of survival from childhood leukaemia for 1995–2009, by subtype, age, and sex (CONCORD-2): a population-based study of individual data for 89 828 children from 198 registries in 53 countries

Background Global inequalities in access to health care are reflected in differences in cancer survival. The CONCORD programme was designed to assess worldwide differences and trends in population-based cancer survival. In this population-based study, we aimed to estimate survival inequalities globally for several subtypes of childhood leukaemia. Methods Cancer registries participating in CONCORD were asked to submit tumour registrations for all children aged 0-14 years who were diagnosed with leukaemia between Jan 1, 1995, and Dec 31, 2009, and followed up until Dec 31, 2009. Haematological malignancies were defined by morphology codes in the International Classification of Diseases for Oncology, third revision. We excluded data from registries from which the data were judged to be less reliable, or included only lymphomas, and data from countries in which data for fewer than ten children were available for analysis. We also excluded records because of a missing date of birth, diagnosis, or last known vital status. We estimated 5-year net survival (ie, the probability of surviving at least 5 years after diagnosis, after controlling for deaths from other causes [background mortality]) for children by calendar period of diagnosis (1995-99, 2000-04, and 2005-09), sex, and age at diagnosis (< 1, 1-4, 5-9, and 10-14 years, inclusive) using appropriate life tables. We estimated age-standardised net survival for international comparison of survival trends for precursor-cell acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). Findings We analysed data from 89 828 children from 198 registries in 53 countries. During 1995-99, 5-year agestandardised net survival for all lymphoid leukaemias combined ranged from 10.6% (95% CI 3.1-18.2) in the Chinese registries to 86.8% (81.6-92.0) in Austria. International differences in 5-year survival for childhood leukaemia were still large as recently as 2005-09, when age-standardised survival for lymphoid leukaemias ranged from 52.4% (95% CI 42.8-61.9) in Cali, Colombia, to 91.6% (89.5-93.6) in the German registries, and for AML ranged from 33.3% (18.9-47.7) in Bulgaria to 78.2% (72.0-84.3) in German registries. Survival from precursor-cell ALL was very close to that of all lymphoid leukaemias combined, with similar variation. In most countries, survival from AML improved more than survival from ALL between 2000-04 and 2005-09. Survival for each type of leukaemia varied markedly with age: survival was highest for children aged 1-4 and 5-9 years, and lowest for infants (younger than 1 year). There was no systematic difference in survival between boys and girls. Interpretation Global inequalities in survival from childhood leukaemia have narrowed with time but remain very wide for both ALL and AML. These results provide useful information for health policy makers on the effectiveness of health-care systems and for cancer policy makers to reduce inequalities in childhood survival