Indexed dependence metadata and its applications in software performance optimisation

To achieve continued performance improvements, modern microprocessor design is tending to concentrate an increasing proportion of hardware on computation units with less automatic management of data movement and extraction of parallelism. As a result, architectures increasingly include multiple computation cores and complicated, software-managed memory hierarchies. Compilers have difficulty characterizing the behaviour of a kernel in a general enough manner to enable automatic generation of efficient code in any but the most straightforward of cases. We propose the concept of indexed dependence metadata to improve application development and mapping onto such architectures. The metadata represent both the iteration space of a kernel and the mapping of that iteration space from a given index to the set of data elements that iteration might use: thus the dependence metadata is indexed by the kernel’s iteration space. This explicit mapping allows the compiler or runtime to optimise the program more efficiently, and improves the program structure for the developer. We argue that this form of explicit interface specification reduces the need for premature, architecture-specific optimisation. It improves program portability, supports intercomponent optimisation and enables generation of efficient data movement code. We offer the following contributions: an introduction to the concept of indexed dependence metadata as a generalisation of stream programming, a demonstration of its advantages in a component programming system, the decoupled access/execute model for C++ programs, and how indexed dependence metadata might be used to improve the programming model for GPU-based designs. Our experimental results with prototype implementations show that indexed dependence metadata supports automatic synthesis of double-buffered data movement for the Cell processor and enables aggressive loop fusion optimisations in image processing, linear algebra and multigrid application case studies

Large-Eddy Simulations of Magnetohydrodynamic Turbulence in Heliophysics and Astrophysics

We live in an age in which high-performance computing is transforming the way we do science. Previously intractable problems are now becoming accessible by means of increasingly realistic numerical simulations. One of the most enduring and most challenging of these problems is turbulence. Yet, despite these advances, the extreme parameter regimes encountered in space physics and astrophysics (as in atmospheric and oceanic physics) still preclude direct numerical simulation. Numerical models must take a Large Eddy Simulation (LES) approach, explicitly computing only a fraction of the active dynamical scales. The success of such an approach hinges on how well the model can represent the subgrid-scales (SGS) that are not explicitly resolved. In addition to the parameter regime, heliophysical and astrophysical applications must also face an equally daunting challenge: magnetism. The presence of magnetic fields in a turbulent, electrically conducting fluid flow can dramatically alter the coupling between large and small scales, with potentially profound implications for LES/SGS modeling. In this review article, we summarize the state of the art in LES modeling of turbulent magnetohydrodynamic (MHD) ows. After discussing the nature of MHD turbulence and the small-scale processes that give rise to energy dissipation, plasma heating, and magnetic reconnection, we consider how these processes may best be captured within an LES/SGS framework. We then consider several special applications in heliophysics and astrophysics, assessing triumphs, challenges,and future directions

Protocol for developing quality assurance measures to use in surgical trials:an example from the ROMIO study

INTRODUCTION: Randomised controlled trials (RCTs) in surgery are frequently criticised because surgeon expertise and standards of surgery are not considered or accounted for during study design. This is particularly true in pragmatic trials (which typically involve multiple centres and surgeons and are based in 'real world' settings), compared with explanatory trials (which are smaller and more tightly controlled).OBJECTIVE: This protocol describes a process to develop and test quality assurance (QA) measures for use within a predominantly pragmatic surgical RCT comparing minimally invasive and open techniques for oesophageal cancer (the NIHR ROMIO study). It builds on methods initiated in the ROMIO pilot RCT.METHODS AND ANALYSIS: We have identified three distinct types of QA measure: (i) entry criteria for surgeons, through assessment of operative videos, (ii) standardisation of operative techniques (by establishing minimum key procedural phases) and (iii) monitoring of surgeons during the trial, using intraoperative photography to document key procedural phases and standardising the pathological assessment of specimens. The QA measures will be adapted from the pilot study and tested iteratively, and the video and photo assessment tools will be tested for reliability and validity.ETHICS AND DISSEMINATION: Ethics approval was obtained (NRES Committee South West-Frenchay, 25 April 2016, ref: 16/SW/0098). Results of the QA development study will be submitted for publication in a peer-reviewed journal.Trial registration number: ISRCTN59036820, ISRCTN10386621.</p

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

Evaluating Post-fire Salvage Logging Effects on Erosion

Legal challenges have delayed numerous post-fire salvage logging operations, which often results in lost economic value of the burned timber and unrecovered legal expenses. The scientific literature has shed little light on the additive effect of salvage logging operations on post-fire runoff, erosion, flooding, and sedimentation. Hence, there is an urgent need to better understand the impacts of post-fire salvage operations so that land managers can evaluate the relative and cumulative effects of different salvage logging practices. Intensive, multi-scale studies are needed because the effects of post-fire logging are superimposed on the effect of wildfires; rates and processes change according to the spatial and temporal scales of the investigation; and the studies to date indicate tremendous variability in the effects of post-fire salvage logging with the type and extent of the logging, site characteristics, and climatic conditions

Clozapine combination and augmentation strategies in patients with schizophrenia: recommendations from an international expert survey among the Treatment Response and Resistance in Psychosis (TRRIP) Working Group

Evidence for the management of inadequate clinical response to clozapine in treatment-resistant schizophrenia is sparse. Accordingly, an international initiative was undertaken with the aim of developing consensus recommendations for treatment strategies for clozapine-refractory patients with schizophrenia