Understanding the role of performance targets in transport policy

The measurement of performance in the public sector has become increasingly important in recent years and it is now commonplace for transport organisations, and local and national governments, to publish performance goals for service supply and quality. Such commitments, when time referenced, are known as targets. This paper explain how changes in management style, consumer rights legislation, contractual obligations and other factors have combined to make management-by targets increasingly common in the public sector. The advantages and disadvantages of management-by-targets are illustrated through discussion of the processes and experience of setting transport targets in UK national transport policy. We conclude that while some of the targets have had a significant impact on policy makers, managers and their agents, the effects have not always been as intended

Results of a randomized, double-blind phase II clinical trial of NY-ESO-1 vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in participants with high-risk resected melanoma.

BACKGROUND: To compare the clinical efficacy of New York Esophageal squamous cell carcinoma-1 (NY-ESO-1) vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in a randomized, double-blind phase II study in participants with fully resected melanoma at high risk of recurrence. METHODS: Participants with resected stage IIc, IIIb, IIIc and IV melanoma expressing NY-ESO-1 were randomized to treatment with three doses of NY-ESO-1/ISCOMATRIX or ISCOMATRIX adjuvant administered intramuscularly at 4-week intervals, followed by a further dose at 6 months. Primary endpoint was the proportion free of relapse at 18 months in the intention-to-treat (ITT) population and two per-protocol populations. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), safety and NY-ESO-1 immunity. RESULTS: The ITT population comprised 110 participants, with 56 randomized to NY-ESO-1/ISCOMATRIX and 54 to ISCOMATRIX alone. No significant toxicities were observed. There were no differences between the study arms in relapses at 18 months or for median time to relapse; 139 vs 176 days (p=0.296), or relapse rate, 27 (48.2%) vs 26 (48.1%) (HR 0.913; 95% CI 0.402 to 2.231), respectively. RFS and OS were similar between the study arms. Vaccine recipients developed strong positive antibody responses to NY-ESO-1 (p≤0.0001) and NY-ESO-1-specific CD4+ and CD8+ responses. Biopsies following relapse did not demonstrate differences in NY-ESO-1 expression between the study populations although an exploratory study demonstrated reduced (NY-ESO-1)+/Human Leukocyte Antigen (HLA) class I+ double-positive cells in biopsies from vaccine recipients performed on relapse in 19 participants. CONCLUSIONS: The vaccine was well tolerated, however, despite inducing antigen-specific immunity, it did not affect survival endpoints. Immune escape through the downregulation of NY-ESO-1 and/or HLA class I molecules on tumor may have contributed to relapse

The transformation of transport policy in Great Britain? 'New Realism' and New Labour's decade of displacement activity

In a 1999 paper, Goodwin announced ‘the transformation of transport policy in Great Britain’. His central point was that consensus was emerging among policy makers and academics based on earlier work including Transport: The New Realism, which rejected previous orthodoxy that the supply of road space could and should be continually expanded to match demand. Instead a combination of investment in public transport, walking and cycling opportunities and – crucially – demand management should form the basis of transport policy to address rising vehicle use and associated increases in congestion and pollution / carbon emissions. This thinking formed the basis of the 1997 Labour government’s ‘sustainable transport’ policy, but after 13 years in power ministers neither transformed policy nor tackled longstanding transport trends. Our main aim in this paper is to revisit the concept of New Realism and re-examine its potential utility as an agent of change in British transport policy. Notwithstanding the outcome of Labour’s approach to transport policy, we find that the central tenets of the New Realism remain robust and that the main barriers to change are related to broader political and governance issues which suppress radical policy innovation

Opening out and closing down: The treatment of uncertainty in transport planning’s forecasting paradigm

© 2019, The Author(s). Since the 1960s, development of the transport system has been framed by the notion of forecasting future demand. Yet the past decade or more appears to signal some significant changes to the role of travel in society which are having a material impact on how much people travel (and may travel in the future). Coupled with the potential for major technological changes and a range of climate adaptation scenarios, the future of mobility presents today’s decision making on transport strategy and investment with a broader set of uncertainties than has previously been considered. This paper examines current mainstream practice for incorporating uncertainty into decision-making, through an illustrative case study of the highly codified approaches of the Department for Transport in England. It deconstructs the issue by first focussing on different ways in which there is an opening out or acceptance of new uncertainties and how this creates a (wider) set of potential futures. It then turns to consider how this set of futures is used, or not, in decision-making, i.e. the process of closing down uncertainty to arrive at or at least inform a decision. We demonstrate that, because the range of uncertainties has broadened in scope and scale, the traditional technocratic approach of closing down decisions through sensitivity testing is at odds with the greater breadth now being called for at the opening out stage. We conclude that transport decision-making would benefit from a rebalancing of technical depth with analytical breadth. The paper outlines a plausible new approach to opening out and closing down that is starting to be applied in practice. This approach must be accompanied by an opening up of the processes by which technical advice for decisions are reached and how uncertainties are understood and negotiated

FLORA: a novel method to predict protein function from structure in diverse superfamilies

Predicting protein function from structure remains an active area of interest, particularly for the structural genomics initiatives where a substantial number of structures are initially solved with little or no functional characterisation. Although global structure comparison methods can be used to transfer functional annotations, the relationship between fold and function is complex, particularly in functionally diverse superfamilies that have evolved through different secondary structure embellishments to a common structural core. The majority of prediction algorithms employ local templates built on known or predicted functional residues. Here, we present a novel method (FLORA) that automatically generates structural motifs associated with different functional sub-families (FSGs) within functionally diverse domain superfamilies. Templates are created purely on the basis of their specificity for a given FSG, and the method makes no prior prediction of functional sites, nor assumes specific physico-chemical properties of residues. FLORA is able to accurately discriminate between homologous domains with different functions and substantially outperforms (a 2–3 fold increase in coverage at low error rates) popular structure comparison methods and a leading function prediction method. We benchmark FLORA on a large data set of enzyme superfamilies from all three major protein classes (α, β, αβ) and demonstrate the functional relevance of the motifs it identifies. We also provide novel predictions of enzymatic activity for a large number of structures solved by the Protein Structure Initiative. Overall, we show that FLORA is able to effectively detect functionally similar protein domain structures by purely using patterns of structural conservation of all residues

Improving the performance of DomainDiscovery of protein domain boundary assignment using inter-domain linker index

BACKGROUND: Knowledge of protein domain boundaries is critical for the characterisation and understanding of protein function. The ability to identify domains without the knowledge of the structure – by using sequence information only – is an essential step in many types of protein analyses. In this present study, we demonstrate that the performance of DomainDiscovery is improved significantly by including the inter-domain linker index value for domain identification from sequence-based information. Improved DomainDiscovery uses a Support Vector Machine (SVM) approach and a unique training dataset built on the principle of consensus among experts in defining domains in protein structure. The SVM was trained using a PSSM (Position Specific Scoring Matrix), secondary structure, solvent accessibility information and inter-domain linker index to detect possible domain boundaries for a target sequence. RESULTS: Improved DomainDiscovery is compared with other methods by benchmarking against a structurally non-redundant dataset and also CASP5 targets. Improved DomainDiscovery achieves 70% accuracy for domain boundary identification in multi-domains proteins. CONCLUSION: Improved DomainDiscovery compares favourably to the performance of other methods and excels in the identification of domain boundaries for multi-domain proteins as a result of introducing support vector machine with benchmark_2 dataset

Dermatofibrosarcoma protuberans treated by micrographic surgery

Dermatofibrosarcoma protuberans is an uncommon cutaneous tumour which rarely metastasises. However, local recurrence following apparently adequate surgical excision is well recognised, presumably as a result of sub-clinical contiguous growth, for which micrographically controlled excision would be a logical treatment. A retrospective study of all patients treated by micrographic surgery, from April 1995–March 2000, at a tertiary skin oncology centre. Twenty-one patients (11 males), age 14 to 71 years with dermatofibrosarcoma protuberans on the trunk (10 patients), groin (four), head and neck (four), and limbs (three) were treated. In 15 patients one micrographic layer cleared the tumour, and four were cleared with two layers. For one patient the second stage was completed by conventional excision guided by positive margins. Another patient with a multiply recurrent perineal dermatofibrosarcoma protuberans, not cleared in one area after two layers, died from a pulmonary embolus before total clearance could be achieved. There was no correlation between tumour size and lateral excision margin. No recurrence was observed during the follow-up, from 21 to 80 months, median 47 months. The study provides further support for micrographic surgery as the treatment of choice for dermatofibrosarcoma protuberans

Sea-level rise impacts on transport infrastructure: the notorious case of the coastal railway line at Dawlish, England

Future climate change is likely to increase the frequency of coastal storms and floods, with major consequences for coastal transport infrastructure. This paper assesses the extent to which projected sea-level rise is likely to impact upon the functioning of the Dawlish to Teignmouth stretch of the London to Penzance railway line, in England. Using a semi-empirical modelling approach, we identify a relationship between sea-level change and rail incidents over the last 150 years and then use model-based sea-level predictions to extrapolate this relationship into the future. We find that days with line restrictions (DLRs) look set to increase by up to 1170%, to as many as 84–120 per year, by 2100 in a high sea-level rise scenario (0.55–0.81 m). Increased costs to the railway industry deriving from maintenance and line restrictions will be small (£ millions) in comparison with damage caused by individual extreme events (£10s of millions), while the costs of diversion of the railway are higher still (£100s of millions to billions). Socio-economic costs to the region are likely to be significant although they are more difficult to estimate accurately. Finally, we explain how our methodology is applicable to vulnerable coastal transport infrastructure worldwide

Rethinking the changing structures of rural local government - state power, rural politics and local political strategies?

Copyright © 2010 Elsevier. NOTICE: this is the author’s version of a work that was accepted for publication in Molecular and Biochemical Parasitology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Rural Studies, 2010, Vol. 26, Issue 3, pp 272–283 DOI: http://dx.doi.org/10.1016/j.jrurstud.2009.12.005There is a notable absence in contemporary rural studies - of both a theoretical and empirical nature - concerning the changing nature of rural local government. Despite the scale and significance of successive rounds of local government reorganisation in the UK, very little has been written on this topic from a rural perspective. Instead research on local political change has tended to concentrate on local governance and local partnerships – on the extra-governmental aspects of the governance system – rather than on local government itself. In contrast, this paper draws upon strategic relational state theory to explore the changing structures and institutions of rural local government, and analyse how these can be related to the changing state strategies of those groups which are politically powerful in rural areas. In this respect, the paper draws on current and previous rounds of local government reorganisation to illustrate how new objects of governance, new state strategies and new hegemonic projects are emerging as a consequence of such restructuring processes

Measurement of the cross-section of high transverse momentum vector bosons reconstructed as single jets and studies of jet substructure in pp collisions at √s = 7 TeV with the ATLAS detector

This paper presents a measurement of the cross-section for high transverse momentum W and Z bosons produced in pp collisions and decaying to all-hadronic final states. The data used in the analysis were recorded by the ATLAS detector at the CERN Large Hadron Collider at a centre-of-mass energy of √s = 7 TeV;{\rm Te}{\rm V}$and correspond to an integrated luminosity of$4.6\;{\rm f}{{{\rm b}}^{-1}}$. The measurement is performed by reconstructing the boosted W or Z bosons in single jets. The reconstructed jet mass is used to identify the W and Z bosons, and a jet substructure method based on energy cluster information in the jet centre-of-mass frame is used to suppress the large multi-jet background. The cross-section for events with a hadronically decaying W or Z boson, with transverse momentum${{p}_{{\rm T}}}\gt 320\;{\rm Ge}{\rm V}$and pseudorapidity$|\eta |\lt 1.9$, is measured to be${{\sigma }_{W+Z}}=8.5\pm 1.7$ pb and is compared to next-to-leading-order calculations. The selected events are further used to study jet grooming techniques