The challenges faced in the design, conduct and analysis of surgical randomised trials

Randomised evaluations of surgical interventions are rare; some interventions have been widely adopted without rigorous evaluation. Unlike other medical areas, the randomised controlled trial (RCT) design has not become the default study design for the evaluation of surgical interventions. Surgical trials are difficult to successfully undertake and pose particular practical and methodological challenges. However, RCTs have played a role in the assessment of surgical innovations and there is scope and need for greater use. This article will consider the design, conduct and analysis of an RCT of a surgical intervention. The issues will be reviewed under three headings: the timing of the evaluation, defining the research question and trial design issues. Recommendations on the conduct of future surgical RCTs are made. Collaboration between research and surgical communities is needed to address the distinct issues raised by the assessment of surgical interventions and enable the conduct of appropriate and well-designed trials

Interplay between finite resources and local defect in an asymmetric simple exclusion process

When particle flux is regulated by multiple factors such as particle supply and varying transport rate, it is important to identify the respective dominant regimes. We extend the well-studied totally asymmetric simple exclusion model to investigate the interplay between a controlled entrance and a local defect site. The model mimics cellular transport phenomena where there is typically a finite particle pool and non-uniform moving rates due to biochemical kinetics. Our simulations reveal regions where, despite an increasing particle supply, the current remains constant while particles redistribute in the system. Exploiting a domain wall approach with mean-field approximation, we provide a theoretical ground for our findings. The results in steady state current and density profiles provide quantitative insights into the regulation of the transcription and translation process in bacterial protein synthesis. We investigate the totally asymmetric simple exclusion model with controlled entrance and a defect site in the bulk to mimic the finite particle pool and non-uniform moving rates in particle transport processes.Comment: 9 pages, 12 figures; v2: minor format changes; v3: major revision, additional references; v4: minor format change to figures, additional reference

Is there any Evidence for Regional Atmospheric 14C Offsets in the Southern Hemisphere?

Center for Accelerator Mass Spectrometry (CAMS) Tasmanian huon pine (Lagarostrobos franklinii) decadal measurements for the interval AD 745–855 suggest a mean interhemispheric radiocarbon offset (20 ± 5 yr), which is considerably lower than the previously reported mean interhemispheric offset for the last 2 millennia (44 ± 17 yr). However, comparable University of Waikato (Wk) New Zealand kauri (Agathis australis) measurements show significantly higher values (56 ± 6 yr), suggesting the possibility of a temporary geographic (intrahemispheric) offset between Tasmania, Australia, and Northland, New Zealand, during at least 1 common time interval. Here, we report 9 new Wk Tasmanian huon pine measurements from the decades showing the largest huon/kauri difference. We show statistically indistinguishable Wk huon and Wk kauri 14C ages, thus dispelling the suggestion of a 14C geographic offset between Tasmania and Northland

Software Process Validation: Quantitatively Measuring the Correspondence of a Process to a Model ; CU-CS-840-97

this article

Discovering Models of Software Processes from Event-Based Data ; CU-CS-819-96

Many software process methods and tools presuppose the existence of a formal model of a process. Unfortunately, developing a formal model for an on-going, complex process can be dicult, costly, and error prone. This presents a practical barrier to the adoption of process technologies, which would be lowered by automated assistance in creating formal models. To this end, we have developed a data analysis technique that we term process discovery. Under this technique, data describing process events are rst captured from an on-going process and then used to generate a formal model of the behavior of that process. In this paper we describe a Markov method that we developed specically for process discovery, as well as describe two additional methods that we adopted from other domains and augmented for our purposes. The three methods range from the purely algorithmic to the purely statistical. We compare the methods and discuss their application in an industrial case study

Evidence for suppressed mid-Holocene northeastern Australian monsoon variability from coral luminescence

Summer monsoon rainfall in northeastern (NE) Australia exhibits substantial interannual variability resulting in highly variable river flows. The occurrence and magnitude of these seasonal river flows are reliably recorded in modern inshore corals as luminescent lines. Here we present reconstructed annual river flows for two ~120 year mid-Holocene windows based on luminescence measurements from five cores obtained from three separate coral colonies. We were able to cross-date the luminescence signatures in four cores from two of the colonies, providing confidence in the derived reconstruction. Present-day NE Australian rainfall and river flow are sensitive to El Niño–Southern Oscillation (ENSO) variability, with La Niña (El Niño) events typically associated with wetter (drier) monsoon seasons. Thus, our replicated and annually resolved coral records provide valuable insights into the northern Australian summer monsoon and ENSO variability at a key period (6 ka) when greenhouse gas levels and ice sheet cover were comparable to the preindustrial period but orbital forcing was different. Average modern and mid-Holocene growth characteristics were very similar, suggesting that sea surface temperatures off NE Australia at 6 kyr were also close to present values. The reconstructed river flow record suggests, however, that the mid-Holocene Australian summer monsoon was weaker, less variable from year to year (possibly indicative of reduced ENSO variability), and characterized by more within-season flood pulses than present. In contrast to today, the delivery of moisture appears to have been dominated by eastward propagating convective coupled waves associated with the Madden-Julian Oscillation

The curious case of an internal pilot in a multicentre randomised trial—time for a rethink?

Multicentre randomised trials are complex projects with many operational uncertainties. The embedding of a formal check upon study progress and viability at a pre-specified time point (sometimes referred to as an 'internal pilot') is becoming increasingly common within multicentre pragmatic randomised trials. However, it is worth considering this practice. We argue that most, if not all, multicentre trials have reassessment of the recruitment strategy and study processes whilst the study is running. Additionally, we propose discontinuation of the 'internal/external pilot study' terminology. Instead, we suggest for an alternative taxonomy along with greater recognition of the process of refinement which routinely occurs in trials and transparent reporting of it

Challenges in evaluating surgical innovation

Research on surgical interventions is associated with several methodological and practical challenges of which few, if any, apply only to surgery. However, surgical evaluation is especially demanding because many of these challenges coincide. In this report, the second of three on surgical innovation and evaluation, we discuss obstacles related to the study design of randomised controlled trials and non-randomised studies assessing surgical interventions. We also describe the issues related to the nature of surgical procedures—for example, their complexity, surgeon-related factors, and the range of outcomes. Although difficult, surgical evaluation is achievable and necessary. Solutions tailored to surgical research and a framework for generating evidence on which to base surgical practice are essential.The Balliol Colloquium has been supported by Ethicon UK with unrestricted educational grants and by the National Institute of Health Research Health Technology Assessment Programme. The Balliol Colloquium was administratively and financially supported by the Nuffield Department of Surgery at the University of Oxford and the Department of Surgery at McGill University. JAC holds a Medical Research Council UK special training fellowship. The University of Aberdeen’s Health Services Research Unit is core funded by the Chief Scientist Offi ce of the Scottish Government Health Directorates. IB is supported by a grant from the Société Française de Rhumatologie and Lavoisier Program (Ministère des Aff aires Etrangères et Européennes). PLE is a DPhil Candidate in Evidence-Based Health Care at Oxford University