Presenting the case for the application of multi-criteria analysis to mega transport infrastructure project appraisal

The paper commences with an overview of mega transport infrastructure decision-making as it relates to the megaproject development cycle and challenges of sustainable development, which are increasingly redefining the criterion for the evaluation of project success. The body of the paper presents a brief critique of various appraisal applications to mega transport infrastructure projects, including: Social Cost Benefit Analysis; Cost Effectiveness Analysis; Goal Achievement Matrix Methods and the Planning Balance Sheet, highlighting the merits and demerits of the outlined approaches. Here particular reference is made to the power of context on decision-making and other lessons from OMEGA Centre research. These include, most importantly, the treatment of risk, uncertainty and complexity of developments outside of the project and the challenges of meeting multiple stakeholder aspirations/needs thereby building up the case for the introduction and use of multi-criteria analysis and policy-led multi-criteria analysis to the appraisal of Mega Transport Projects

Application of policy-led multi-criteria analysis to the appraisal of the Northern Line Extension, London

This paper seeks to both illustrate and act as a proof of concept of how a policy-led multi-criteria analysis framework and its attendant process of the type introduced in the second paper, ‘Theory and Background of Multi-Criteria Analysis: Toward a policy-led approach for mega transport project infrastructure appraisal’, can be applied to the appraisal of a mega transport project in the form of the Northern Line Extension in London. It is offered with a view to help better identify the distribution of the projects costs and benefits and shed greater light on the possible ‘winners’ and ‘losers’ over space and time, and under given scenarios. Drawing from an extensive array of public domain literature the paper sets out both the policy and planning contexts for the project plus the business case that led to a decision by UK Treasury to guarantee a £1 billion loan to Transport for London for the construction of the Northern Line's extension. The paper looks at the scale and nature of the megaproject's features, particularly its line-haul and related real estate developments, especially those in the assigned development opportunity area. The text presents the policy, planning, legislative and regulative dimensions of the project likely to define its revenue generation prospects and environmental and social impacts, with special attention paid to those project outcomes affecting key stakeholders over time and space. The paper also seeks to explain the mechanics of how to employ a policy-led multi-criteria framework together with its associated processes within which stakeholder policies and agendas can be mapped and common/divergent interests identified. This is done with a view to ultimately facilitate stakeholder negotiation decision-making trade-offs in given scenarios under the policy guidance of the Greater London Authority with the support of the Treasury of the UK Government

Goal setting and strategies to enhance goal pursuit for adults with acquired disability participating in rehabilitation.

Published onlineJournal ArticleMeta-AnalysisResearch Support, Non-U.S. Gov'tReviewBACKGROUND: Goal setting is considered a key component of rehabilitation for adults with acquired disability, yet there is little consensus regarding the best strategies for undertaking goal setting and in which clinical contexts. It has also been unclear what effect, if any, goal setting has on health outcomes after rehabilitation. OBJECTIVES: To assess the effects of goal setting and strategies to enhance the pursuit of goals (i.e. how goals and progress towards goals are communicated, used, or shared) on improving health outcomes in adults with acquired disability participating in rehabilitation. SEARCH METHODS: We searched CENTRAL, MEDLINE, EMBASE, four other databases and three trials registers to December 2013, together with reference checking, citation searching and contact with study authors to identify additional studies. We did not impose any language or date restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs), cluster-RCTs and quasi-RCTs evaluating the effects of goal setting or strategies to enhance goal pursuit in the context of adult rehabilitation for acquired disability. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed search results for inclusion. Grey literature searches were conducted and reviewed by a single author. Two authors independently extracted data and assessed risk of bias for included studies. We contacted study authors for additional information. MAIN RESULTS: We included 39 studies (27 RCTs, 6 cluster-RCTs, and 6 quasi-RCTs) involving 2846 participants in total. Studies ranged widely regarding clinical context and participants' primary health conditions. The most common health conditions included musculoskeletal disorders, brain injury, chronic pain, mental health conditions, and cardiovascular disease.Eighteen studies compared goal setting, with or without strategies to enhance goal pursuit, to no goal setting. These studies provide very low quality evidence that including any type of goal setting in the practice of adult rehabilitation is better than no goal setting for health-related quality of life or self-reported emotional status (8 studies; 446 participants; standardised mean difference (SMD) 0.53, 95% confidence interval (CI) 0.17 to 0.88, indicative of a moderate effect size) and self-efficacy (3 studies; 108 participants; SMD 1.07, 95% CI 0.64 to 1.49, indicative of a moderate to large effect size). The evidence is inconclusive regarding whether goal setting results in improvements in social participation or activity levels, body structure or function, or levels of patient engagement in the rehabilitation process. Insufficient data are available to determine whether or not goal setting is associated with more or fewer adverse events compared to no goal setting.Fourteen studies compared structured goal setting approaches, with or without strategies to enhance goal pursuit, to 'usual care' that may have involved some goal setting but where no structured approach was followed. These studies provide very low quality evidence that more structured goal setting results in higher patient self-efficacy (2 studies; 134 participants; SMD 0.37, 95% CI 0.02 to 0.71, indicative of a small effect size) and low quality evidence for greater satisfaction with service delivery (5 studies; 309 participants; SMD 0.33, 95% CI 0.10 to 0.56, indicative of a small effect size). The evidence was inconclusive regarding whether more structured goal setting approaches result in higher health-related quality of life or self-reported emotional status, social participation, activity levels, or improvements in body structure or function. Three studies in this group reported on adverse events (death, re-hospitalisation, or worsening symptoms), but insufficient data are available to determine whether structured goal setting is associated with more or fewer adverse events than usual care.A moderate degree of heterogeneity was observed in outcomes across all studies, but an insufficient number of studies was available to permit subgroup analysis to explore the reasons for this heterogeneity. The review also considers studies which investigate the effects of different approaches to enhancing goal pursuit, and studies which investigate different structured goal setting approaches. It also reports on secondary outcomes including goal attainment and healthcare utilisation. AUTHORS' CONCLUSIONS: There is some very low quality evidence that goal setting may improve some outcomes for adults receiving rehabilitation for acquired disability. The best of this evidence appears to favour positive effects for psychosocial outcomes (i.e. health-related quality of life, emotional status, and self-efficacy) rather than physical ones. Due to study limitations, there is considerable uncertainty regarding these effects however, and further research is highly likely to change reported estimates of effect

Theory and Background of Multi-Criteria Analysis: Toward a policy-led approach for mega transport project infrastructure appraisal

The aims of this paper are twofold. Firstly, to present a review and critical analysis of the varying forms and functions of Multi-Criteria Analysis presented in the literature, and secondly, drawing from this, to introduce methods and processes by which policy leadership can be introduced into such processes for the appraisal of large-scale transport infrastructure projects to form a policy-led multi-criteria analysis. Following the discussion in the first paper of this Special Issue, ‘Presenting the Case for the Application of Multi-Criteria Analysis to Mega Transport Project Infrastructure Appraisal’, this contribution commences by outlining further the generic features and challenges of multi-criteria analysis approaches to project appraisal whilst emphasizing the difference among various frameworks and attendant processes for such approaches. It also highlights the important role/value of the multi-criteria mapping of stakeholder policies and agendas affecting project decision-making as a means of defining and scoping the boundaries of the project exercise under study and the trade-off decision-spaces for stakeholder dialogues and negotiations in their search to arrive at mutually agreed actions and outcomes. The paper discusses how multi-criteria analysis frameworks can be tailor-designed for particular agencies and stakeholders developed around problems, challenges and issues. This is done in the acknowledgement that such exercises, especially when applied to mega infrastructure project appraisal, typically attract a multiple-institutional response and where ultimately an institutional leader (or partnership of stakeholders) exists/emerges that impose its/their priorities on others. Alternatively, the approach can be tailor-made for specific institutions with its imbedded hierarchy of policies and priorities that frame the stakeholder decision space within which other parties can participate and trade off interests. The first part of the paper highlights the important role of scenarios of policy-making contexts and policy leadership indicating the new risks, uncertainties and opportunities these may offer in multi-criteria analysis exercises, indicating that some/many past processes have been conducted outside of any real reference to such matters. In so doing, such applications have them silently and implicitly adopt scenarios and policy assumptions that are not transparent frequently reflecting, it is alleged, ‘business as usual’ circumstances in contexts when the signs are very much that these trends will not/cannot prevail. The authors contend that without explicit policy leadership there is a danger that certain institutional stakeholder priorities will be imposed over others by the most powerful without adequate dialogue. Understanding that this matters a great deal in contexts when project stakeholder powers shifts occur is very significant. Examples of such circumstances are when national governments become, less or more powerful and economically affluent, when relative legislative and regulation powers become less or more binding and powerful, and when a major private sector investor upon which a project depends goes bankrupt. The second half of the paper builds on these observations to offer a generic multi-criteria analysis framework and attendant processes that imbed policy leadership firmly within multi-stakeholder decision-making (termed Policy-led Multi-criteria Analysis). The framework developed is to be applied to mega transport projects via the use of suitable appraisal criteria in the pursuit of sustainable development goals, which seek to address both quantitative and qualitative dimensions and concerns of multiple stakeholders, with particular emphasis on the processes required to identify and incorporate suitable policy leadership, including feedback between appraisal and policy

Deciphering interplay between Salmonella invasion effectors

Bacterial pathogens have evolved a specialized type III secretion system (T3SS) to translocate virulence effector proteins directly into eukaryotic target cells. Salmonellae deploy effectors that trigger localized actin reorganization to force their own entry into non-phagocytic host cells. Six effectors (SipC, SipA, SopE/2, SopB, SptP) can individually manipulate actin dynamics at the plasma membrane, which acts as a ‘signaling hub’ during Salmonella invasion. The extent of crosstalk between these spatially coincident effectors remains unknown. Here we describe trans and cis binary entry effector interplay (BENEFIT) screens that systematically examine functional associations between effectors following their delivery into the host cell. The results reveal extensive ordered synergistic and antagonistic relationships and their relative potency, and illuminate an unexpectedly sophisticated signaling network evolved through longstanding pathogen–host interaction

Macrophages orchestrate the expansion of a proangiogenic perivascular niche during cancer progression

Tumor-associated macrophages (TAMs) are a highly plastic stromal cell type that support cancer progression. Using single-cell RNA sequencing of TAMs from a spontaneous murine model of mammary adenocarcinoma (MMTV-PyMT), we characterize a subset of these cells expressing lymphatic vessel endothelial hyaluronic acid receptor 1 (Lyve-1) that spatially reside proximal to blood vasculature. We demonstrate that Lyve-1+ TAMs support tumor growth and identify a pivotal role for these cells in maintaining a population of perivascular mesenchymal cells that express α-smooth muscle actin and phenotypically resemble pericytes. Using photolabeling techniques, we show that mesenchymal cells maintain their prevalence in the growing tumor through proliferation and uncover a role for Lyve-1+ TAMs in orchestrating a selective platelet-derived growth factor–CC–dependent expansion of the perivascular mesenchymal population, creating a proangiogenic niche. This study highlights the inter-reliance of the immune and nonimmune stromal network that supports cancer progression and provides therapeutic opportunities for tackling the disease

Pathways to new drug discovery in neuropsychiatry

There is currently a crisis in drug discovery for neuropsychiatric disorders, with a profound, yet unexpected drought in new drug development across the spectrum. In this commentary, the sources of this dilemma and potential avenues to redress the issue are explored. These include a critical review of diagnostic issues and of selection of participants for clinical trials, and the mechanisms for identifying new drugs and new drug targets. Historically, the vast majority of agents have been discovered serendipitously or have been modifications of existing agents. Serendipitous discoveries, based on astute clinical observation or data mining, remain a valid option, as is illustrated by the suggestion in the paper by Wahlqvist and colleagues that treatment with sulfonylurea and metformin reduces the risk of affective disorder. However, the identification of agents targeting disorder-related biomarkers is currently proving particularly fruitful. There is considerable hope for genetics as a purist, pathophysiologically valid pathway to drug discovery; however, it is unclear whether the science is ready to meet this promise. Fruitful paradigms will require a break from the orthodoxy, and creativity and risk may well be the fingerprints of success

Genetic diversity of Brazilian isolates of feline immunodeficiency virus

We isolated Feline immunodeficiency virus (FIV) from three adult domestic cats, originating from two open shelters in Brazil. Viruses were isolated from PBMC following co-cultivation with the feline T-lymphoblastoid cell line MYA-1. All amplified env gene products were cloned directly into pGL8MYA. The nucleic acid sequences of seven clones were determined and then compared with those of previously described isolates. The sequences of all of the Brazilian virus clones were distinct and phylogenetic analysis revealed that all belong to subtype B. Three variants isolated from one cat and two variants were isolated from each of the two other cats, indicating that intrahost diversity has the potential to pose problems for the treatment and diagnosis of FIV infection

Electron quantum metamaterials in van der Waals heterostructures

In recent decades, scientists have developed the means to engineer synthetic periodic arrays with feature sizes below the wavelength of light. When such features are appropriately structured, electromagnetic radiation can be manipulated in unusual ways, resulting in optical metamaterials whose function is directly controlled through nanoscale structure. Nature, too, has adopted such techniques -- for example in the unique coloring of butterfly wings -- to manipulate photons as they propagate through nanoscale periodic assemblies. In this Perspective, we highlight the intriguing potential of designer sub-electron wavelength (as well as wavelength-scale) structuring of electronic matter, which affords a new range of synthetic quantum metamaterials with unconventional responses. Driven by experimental developments in stacking atomically layered heterostructures -- e.g., mechanical pick-up/transfer assembly -- atomic scale registrations and structures can be readily tuned over distances smaller than characteristic electronic length-scales (such as electron wavelength, screening length, and electron mean free path). Yet electronic metamaterials promise far richer categories of behavior than those found in conventional optical metamaterial technologies. This is because unlike photons that scarcely interact with each other, electrons in subwavelength structured metamaterials are charged, and strongly interact. As a result, an enormous variety of emergent phenomena can be expected, and radically new classes of interacting quantum metamaterials designed

Male circumcision and penile cancer: a systematic review and meta-analysis

OBJECTIVE: We systematically reviewed the evidence of an association between male circumcision and penile cancer. METHODS: Databases were searched using keywords and text terms for the epidemiology of penile cancer. Random effects meta-analyses were used to calculate summary odds ratios (ORs) and 95% confidence intervals (CI). RESULTS: We identified eight papers which evaluated the association of circumcision with penile cancer, of which seven were case-control studies. There was a strong protective effect of childhood/adolescent circumcision on invasive penile cancer (OR = 0.33; 95% CI 0.13-0.83; 3 studies). In two studies, the protective effect of childhood/adolescent circumcision on invasive cancer no longer persisted when analyses were restricted to boys with no history of phimosis. In contrast, there was some evidence that circumcision in adulthood was associated with an increased risk of invasive penile cancer (summary OR = 2.71; 95% CI 0.93-7.94; 3 studies). There was little evidence for an association of penile intra-epithelial neoplasia and in situ penile cancer with circumcision performed at any age. CONCLUSIONS: Men circumcised in childhood/adolescence are at substantially reduced risk of invasive penile cancer, and this effect could be mediated partly through an effect on phimosis. Expansion of circumcision services in sub-Saharan Africa as an HIV prevention strategy may additionally reduce penile cancer risk