Comparing open and minimally invasive surgical procedures for oesophagectomy in the treatment of cancer: the ROMIO (Randomised Oesophagectomy: Minimally Invasive or Open) feasibility study and pilot trial

Localised oesophageal cancer can be curatively treated with surgery (oesophagectomy) but the procedure is complex with a risk of complications, negative effects on quality of life and a recovery period of 6-9 months. Minimal-access surgery may accelerate recovery.The ROMIO (Randomised Oesophagectomy: Minimally Invasive or Open) study aimed to establish the feasibility of, and methodology for, a definitive trial comparing minimally invasive and open surgery for oesophagectomy. Objectives were to quantify the number of eligible patients in a pilot trial; develop surgical manuals as the basis for quality assurance; standardise pathological processing; establish a method to blind patients to their allocation in the first week post surgery; identify measures of postsurgical outcome of importance to patients and clinicians; and establish the main cost differences between the surgical approaches.Pilot parallel three-arm randomised controlled trial nested within feasibility work.Two UK NHS departments of upper gastrointestinal surgery.Patients aged ≥ 18 years with histopathological evidence of oesophageal or oesophagogastric junctional adenocarcinoma, squamous cell cancer or high-grade dysplasia, referred for oesophagectomy or oesophagectomy following neoadjuvant chemo(radio)therapy.Oesophagectomy, with patients randomised to open surgery, a hybrid open chest and minimally invasive abdomen or totally minimally invasive access.The primary outcome measure for the pilot trial was the number of patients recruited per month, with the main trial considered feasible if at least 2.5 patients per month were recruited.During 21 months of recruitment, 263 patients were assessed for eligibility; of these, 135 (51%) were found to be eligible and 104 (77%) agreed to participate, an average of five patients per month. In total, 41 patients were allocated to open surgery, 43 to the hybrid procedure and 20 to totally minimally invasive surgery. Recruitment is continuing, allowing a seamless transition into the definitive trial. Consequently, the database is unlocked at the time of writing and data presented here are for patients recruited by 31 August 2014. Random allocation achieved a good balance between the arms of the study, which, as a high proportion of patients underwent their allocated surgery (69/79, 87%), ensured a fair comparison between the interventions. Dressing patients with large bandages, covering all possible incisions, was successful in keeping patients blind while pain was assessed during the first week post surgery. Postsurgical length of stay and risk of adverse events were within the typical range for this group of patients, with one death occurring within 30 days among 76 patients. There were good completion rates for the assessment of pain at 6 days post surgery (88%) and of the patient-reported outcomes at 6 weeks post randomisation (74%).Rapid recruitment to the pilot trial and the successful refinement of methodology indicated the feasibility of a definitive trial comparing different approaches to oesophagectomy. Although we have shown a full trial of open compared with minimally invasive oesophagectomy to be feasible, this is necessarily based on our findings from the two clinical centres that we could include in this small preliminary study.Current Controlled Trials ISRCTN59036820.This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 48. See the NIHR Journals Library website for further project information

Combining satellite observations and reanalysis energy transports to estimate global net surface energy fluxes 1985-2012

Two methods are developed to estimate net surface energy fluxes based upon satellite-based reconstructions of radiative fluxes at the top of atmosphere and the atmospheric energy tendencies and transports from the ERA-Interim reanalysis. Method 1 applies the mass adjusted energy divergence from ERA-Interim while method 2 estimates energy divergence based upon the net energy difference at the top of atmosphere and the surface from ERA-Interim. To optimise the surface flux and its variability over ocean, the divergences over land are constrained to match the monthly area mean surface net energy flux variability derived from a simple relationship between the surface net energy flux and the surface temperature change. The energy divergences over the oceans are then adjusted to remove an unphysical residual global mean atmospheric energy divergence. The estimated net surface energy fluxes are compared with other data sets from reanalysis and atmospheric model simulations. The spatial correlation coefficients of multi-annual means between the estimations made here and other data sets are all around 0.9. There are good agreements in area mean anomaly variability over the global ocean, but discrepancies in the trend over the eastern Pacific are apparent

Multi-scale waves in sound-proof global simulations with EULAG

EULAG is a computational model for simulating flows across a wide range of scales and physical scenarios. A standard option employs an anelastic approximation to capture nonhydrostatic effects and simultaneously filter sound waves from the solution. In this study, we examine a localized gravity wave packet generated by instabilities in Held-Suarez climates. Although still simplified versus the Earth’s atmosphere, a rich set of planetary wave instabilities and ensuing radiated gravity waves can arise. Wave packets are observed that have lifetimes ≤ 2 days, are negligibly impacted by Coriolis force, and do not show the rotational effects of differential jet advection typical of inertia-gravity waves. Linear modal analysis shows that wavelength, period, and phase speed fit the dispersion equation to within a mean difference of ∼ 4%, suggesting an excellent fit. However, the group velocities match poorly even though a propagation of uncertainty analysis indicates that they should be predicted as well as the phase velocities. Theoretical arguments suggest the discrepancy is due to nonlinearity — a strong southerly flow leads to a critical surface forming to the southwest of the wave packet that prevents the expected propagation

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

The role of horizontal resolution in simulating drivers of the global hydrological cycle

The role of atmospheric general circulation model (AGCM) horizontal resolution in representing the global energy budget and hydrological cycle is assessed, with the aim of improving the understanding of model uncertainties in simulating the hydrological cycle. We use two AGCMs from the UK Met Office Hadley Centre: HadGEM1-A at resolutions ranging from 270 to 60 km, and HadGEM3-A ranging from 135 to 25 km. The models exhibit a stable hydrological cycle, although too intense compared to reanalyses and observations. This over-intensity is explained by excess surface shortwave radiation, a common error in general circulation models (GCMs). This result is insensitive to resolution. However, as resolution is increased, precipitation decreases over the ocean and increases over the land. This is associated with an increase in atmospheric moisture transport from ocean to land, which changes the partitioning of moisture fluxes that contribute to precipitation over land from less local to more non-local moisture sources. The results start to converge at 60-km resolution, which underlines the excessive reliance of the mean hydrological cycle on physical parametrization (local unresolved processes) versus model dynamics (large-scale resolved processes) in coarser HadGEM1 and HadGEM3 GCMs. This finding may be valid for other GCMs, showing the necessity to analyze other chains of GCMs that may become available in the future with such a range of horizontal resolutions. Our finding supports the hypothesis that heterogeneity in model parametrization is one of the underlying causes of model disagreement in the Coupled Model Intercomparison Project (CMIP) exercises

CCP4 Cloud for structure determination and project management in macromolecular crystallography

Nowadays, progress in the determination of three-dimensional macromolecular structures from diffraction images is achieved partly at the cost of increasing data volumes. This is due to the deployment of modern high-speed, high-resolution detectors, the increased complexity and variety of crystallographic software, the use of extensive databases and high-performance computing. This limits what can be accomplished with personal, offline, computing equipment in terms of both productivity and maintainability. There is also an issue of long-term data maintenance and availability of structure-solution projects as the links between experimental observations and the final results deposited in the PDB. In this article, CCP4 Cloud, a new front-end of the CCP4 software suite, is presented which mitigates these effects by providing an online, cloud-based environment for crystallographic computation. CCP4 Cloud was developed for the efficient delivery of computing power, database services and seamless integration with web resources. It provides a rich graphical user interface that allows project sharing and long-term storage for structure-solution projects, and can be linked to data-producing facilities. The system is distributed with the CCP4 software suite version 7.1 and higher, and an online publicly available instance of CCP4 Cloud is provided by CCP4.The following funding is acknowledged: Biotechnology and Biological Sciences Research Council (grant No. BB/L007037/1; grant No. BB/S007040/1; grant No. BB/S007083/1; grant No. BB/S005099/1; grant No. BB/S007105/1; award No. BBF020384/1); Medical Research Council (grant No.MC_UP_A025_1012; grant No. MC_U105184325); Ro¨ntgenA˚ ngstro¨m Cluster (grant No. 349-2013-597); Nederlandse Wetenschappelijke Organisatie (grant No. TKI 16219)