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In 2017 the Scottish Government passed the Child Poverty (Scotland) Act with the commitment to significantly reduce the relative child poverty rate from the current prevailing level of around 25% to 10% by 2030/31. In response, the government introduced the Scottish Child Payment (SCP) that provides a direct transfer to households at a fixed rate per eligible child – currently £25 per week. In this paper we explore, using a micro to macro modelling approach, the effectiveness of using the SCP to achieve the Scottish child poverty targets. While we find that the ambitious child poverty targets can technically be met solely using the SCP, the necessary payment of £165 per week amounting to a total government cost of £3 billion per year, makes the political and economy-wide barriers significant. A key issue with only using the SCP is the non-linearity in the response to the payment; as the payment increases, the marginal gain in the reduction of child poverty decreases – this is particularly evident after payments of £80 per week. A ‘policy-mix’ option combining the SCP, targeted cash transfers and other policy levels (such as childcare provision) seems the most promising approach to reaching the child poverty targets.

While investment in social housing is mentioned in the Government’s white paper on levelling up, it does not receive the emphasis extended to infrastructure investment. Traditionally, the case for affordable housing was based on merit goods arguments. While the economic effects of housing have been explored, this has mainly been through traditional economic impact studies whose perceived weakness has led to a degree of policy scepticism around the findings of such studies. Recently, however, a strong case has been made for treating investment in housing on a comparable basis to infrastructure on the basis of its potentially important impacts on the supply side, stimulating labour supply and productivity. The purpose of this paper is to evaluate the potential economic impacts of meeting the projections of affordable housing needed in Scotland to combat homelessness using a framework that overcomes the weaknesses of conventional impact analyses.

Regional development now encompasses inclusive growth so that welfare spending becomes a potentially important policy for regions with devolved powers. Universal Basic Income (UBI), an unconditional payment to all citizens, has been gaining traction, including internationally. We provide a system-wide analysis of a region-specific UBI for Scotland on the level and distribution of regional activity. Using both micro- and macro-economic models we find that, although UBI has a beneficial effect on equity among households, it may adversely impact the level of economic activity unless there is a social contract in place and/ or there is a substantial stimulus to productivity.

As well as their role in contributing towards emissions reductions targets, it is increasingly relevant for policymakers to understand the contribution that renewable energy technologies make to the economy. Various methods have been used to quantify impacts, such as job counts, surveys and measures based on economic statistics. Economic modelling approaches on the other hand appear to offer an ability to both provide metrics of interest to policymakers and crucially an understanding of the activities which support that contribution. In this paper, we implement a new method for estimating the activity supported by renewable energy activities; applying a ‘hypothetical extraction’ of offshore wind—to identify the contribution that such activities make to U.K. economic activity, job quality and national emissions. By undertaking the partial extraction of offshore wind from an aggregated input–output (IO) table and then subsequently from one in which we have separated out the offshore wind electricity sector, we highlight the value of more disaggregation and technology‐specific detail in economic accounts. The results from our fullest extraction suggest that in 2010, offshore wind in the United Kingdom supported 10 240 jobs, with 9 in 10 of these jobs either medium or high skill, and contributed £780 million to gross domestic product (GDP). In addition, a significant portion of activity supported by offshore wind is attributable to expansions in capacity rather than operational activities.

Internal iliac artery aneurysms (IIAAs), isolated or associated with abdominal aortic aneurysms, are at rupture risk with growth. Treatment is recommended when symptomatic or greater than3 cm. Surgical or endovascular therapy should exclude the arterial origin and outflow branches. If all outflow branches are not completely embolized, an endoleak can develop, pressurizing the sac leading to growth and rupture. Accessing the arteries involvedcan be technically challenging and understanding potential targets is critical. We describe two percutaneous approaches for treatment: percutaneously accessing the sac from an anterior trans-iliopsoas approach and percutaneously accessing the gluteal artery from a posterior approach.

Chitinase-3-like protein 1 (CHI3L1/YKL-40) has long been known as a biomarker for early detection of neuroinflammation and disease diagnosis of Alzheimer’s disease (AD). In the brain, CHI3L1 is primarily provided by astrocytes and heralds the reactive, neurotoxic state triggered by inflammation and other stress signals. However, how CHI3L1 acts in neuroinflammation or how it contributes to AD and relevant neurodegenerative conditions remains unknown. In peripheral tissues, our group and others have uncovered that CHI3L1 is a master regulator for a wide range of injury and repair events, including the innate immunity pathway that resembles the neuroinflammation process governed by microglia and astrocytes. Based on assessment of current knowledge regarding CHI3L1 biology, we hypothesize that CHI3L1 functions as a signaling molecule mediating distinct neuroinflammatory responses in brain cells and dysfunctions to precipitate the neurodegeneration. We also recommend future research directions to validate such assertions for better understanding of disease mechanism.

Within the system of national accounts the electricity sector is typically reported as a single entry representing generation, transmission, distribution and trade. The ways in which these components interact with the economy differ greatly, a feature lost within the standard accounting framework. In this paper we propose an Electricity Satellite Account (ELSA) approach to better understand the linkages between the electricity sector and economy, with a particular focus on generation technologies. In developing this framework, we draw parallels with Tourism Satellite Accounts (TSAs). To illustrate the practical steps in constructing ELSAs, we develop an ELSA for Scotland for 2012, and show how the ELSA framework gives an improved understanding of the economic contribution of the electricity sector, which is critical in improving the usefulness of such accounts for climate, energy, and economic policy.

In Alzheimer's disease (AD) and other neurodegenerative disorders, oligodendroglial failure is a common early pathological feature, but how it contributes to disease development and progression, particularly in the gray matter of the brain, remains largely unknown. The dysfunction of oligodendrocyte lineage cells is hallmarked by deficiencies in myelination and impaired self-renewal of oligodendrocyte precursor cells (OPCs). These two defects are caused at least in part by the disruption of interactions between neuron and oligodendrocytes along the buildup of pathology. OPCs give rise to myelinating oligodendrocytes during CNS development. In the mature brain cortex, OPCs are the major proliferative cells (comprising ~5% of total brain cells) and control new myelin formation in a neural activity-dependent manner. Such neuron-to-oligodendrocyte communications are significantly understudied, especially in the context of neurodegenerative conditions such as AD, due to the lack of appropriate tools. In recent years, our group and others have made significant progress to improve currently available protocols to generate functional neurons and oligodendrocytes individually from human pluripotent stem cells. In this manuscript, we describe our optimized procedures, including the establishment of a co-culture system to model the neuron-oligodendrocyte connections. Our illustrative results suggest an unexpected contribution from OPCs/oligodendrocytes to the brain amyloidosis and synapse integrity and highlight the utility of this methodology for AD research. This reductionist approach is a powerful tool to dissect the specific hetero-cellular interactions out of the inherent complexity inside the brain. The protocols we describe here are expected to facilitate future studies on oligodendroglial defects in the pathogenesis of neurodegeneration.

The Scottish electricity network is currently in a transition towards becoming 100% renewable. Offshore wind, due to a large natural resource, is expected to be key in this transition. In addition to the anticipated environmental benefits, increasing the share of offshore wind is expected to bring economic benefits to the region. In this study two multi-sectoral modelling methodologies – Input-Output (IO) and Computable General Equilibrium (CGE) – are used to measure the potential economic impacts on Scotland arising from both the construction and operation of the planned increase offshore wind capacity between 2018 and 2025, with comparisons made between models and development stages. With the focus on the benefits to the Scottish economy it is important to focus only on expenditures within Scotland. Found using both IO and (forward-looking and myopic) CGE modelling techniques, is increasing offshore wind capacity raises both employment and Gross Value Added (GVA) with the magnitude and timing of this change critically depend on model type and closure. This is the first – to the author’s knowledge – of a Scottish specific modelling which helps policy makers understand those elements which could affect the possible economic success of current policy towards offshore wind.

We explore, through simulation of a purpose-built Input-Output model of the UK, the economic and emissions impacts of the likely future development of the UK’s offshore wind sector, with a particular emphasis on the importance of local content. We explore six scenarios, including two illustrative simulations of the potential impact of Brexit on local content. We find that future offshore wind development does indeed generate a policy “double dividend” in the form of simultaneous and substantial reductions in cumulative emissions, which in each case exceed a year of the UK’s total emissions, and improvements in economic activity (of nearly £30 billion cumulative increase in value-added when the 60% target for local content is achieved). It is also the case that, as anticipated, the scale of the economic stimulus arising from offshore wind development is directly and strongly related to the extent of local content. Future work could extend the modelling to relax the supply side assumptions of input-output modelling, disaggregate the analysis by regions and households to allow assessment of the impacts on the distribution of both economic activity across regions and income among household quintiles.

Experts from wine tasters to radiologists to bird watchers have all undergone perceptual learning—that is, long-term changes in perception that result from practice or experience. Philosophers have been discussing such cases for centuries, from the fourteenth-century Indian philosopher Vedānta Deśika to the eighteenth-century Scottish philosopher Thomas Reid to a great many contemporary philosophers. This book uses recent evidence from psychology and neuroscience to show that perceptual learning is genuinely perceptual, rather than post-perceptual. It also offers a way for philosophers to distinguish between various different types of it, from changes in how one attends to the learned ability to differentiate two properties or to perceive two properties as unified. The book illustrates how this taxonomy can classify cases in the philosophical literature, and then it rethinks several domains in the philosophy of perception in terms of perceptual learning, including multisensory perception, color perception, and speech perception. As a whole, it offers a new philosophical theory of the function of perceptual learning. Perceptual learning embeds into our quick perceptual systems what would be a slower task were it to be done in a controlled, cognitive manner. A novice wine taster drinking a Cabernet Sauvignon may have to think about its features first and then infer the type of wine it is, while an expert identifies it immediately. Perceptual learning frees up cognitive resources for other tasks, such as thinking about the vineyard or the vintage of the wine. All in all, this book explores the nature, scope, and theoretical implications of perceptual learning.

This chapter argues that multisensory perceptions are learned, not the result of an automatic feature binding mechanism. For example, suppose you are at a live jazz show. The drummer begins a solo. You see the cymbal jolt and hear the clang. But you are also aware that the jolt and the clang are part of the same event. Psychologists have assumed that multisensory perceptions like this one are the result of an automatic feature binding mechanism. This chapter argues instead that when you experience the jolt and the clang as part of the same event, it is the result of a perceptual learning process. The jolt and the clang are best understood as a single learned perceptual unit, not as automatically bound. This chapter details the perceptual learning process of “unitization,” whereby we come to “chunk” the world into multisensory units, and argues that unitization best explains multisensory perception.

This chapter details the role perceptual learning plays in speech perception and argues that the evidence does not show that meanings come to be represented in our perception upon learning a new language. Specifically, it outlines the role of the perceptual learning mechanism of differentiation in speech perception. Through differentiation, we come to parse features of a language, including phonemes that we had not previously differentiated. The chapter critically evaluates Casey O’Callaghan’s and Berit Brogaards’s arguments for and against the view that meanings come to be represented in our perception upon learning a new language. It argues that the evidence from perceptual learning does not support the conclusion that meanings come to be represented in our perception.

This chapter explores the relationship between sensory substitution devices and the training of attention. Sensory substitution devices, typically used by the blind, deliver information about the environment by converting the information normally received through one sense (e.g., vision) into information for another sense (e.g., audition or touch). When a user integrates a sensory substitution device into her life, the integration process involves perceptual learning. This chapter explores two questions. First, in what ways can sensory substitution illuminate how the training of attention works more generally? Second, how does knowledge of the way attention is trained in perceptual learning help us to better understand sensory substitution? The chapter draws on findings in these areas to answer a philosophical question: Should the post-perceptual learning experience be classified in the substituted modality (e.g., as vision), in the substituting modality (e.g., as auditory or tactile), or in a new sense modality?

The concluding chapter argues that perceptual learning has relevance for philosophy far beyond philosophy of mind—in epistemology, philosophy of science, and social philosophy, among other domains. The goal of this chapter is to extend one major focus of the book, which is to identify the scope of perceptual learning. Chapters 3 through 7 argued that perceptual learning occurs in all sorts of domains in the philosophy of mind, including natural kind recognition, sensory substitution, multisensory perception, speech perception, and color perception. This chapter extends that scope beyond philosophy of mind and offers some initial sketches of ways in which we can apply knowledge of perceptual learning to those domains.

This introductory chapter explains perceptual learning as long-term changes in perception that are the result of practice or experience. It distinguishes perceptual learning from other nearby concepts, including perceptual development and cognitive penetration. It then delineates different kinds of perceptual learning. For instance, some kinds of perceptual learning involve changes in how one attends, while other cases involve a learned ability to differentiate two properties, or to perceive two properties as unified. The chapter uses this taxonomy to distinguish different cases of perceptual learning in the philosophical literature, including by contemporary philosophers such as Susanna Siegel, Christopher Peacocke, and Charles Siewert. Finally, it outlines the function of perceptual learning. Perceptual learning serves to offload onto our quick perceptual systems what would be a slower and more cognitively taxing task were it to be done in a controlled, deliberate manner. The upshot is that this frees up cognitive resources for other tasks.

This chapter argues that there are widespread changes in perception due to learning, and that these changes are genuinely perceptual rather than post-perceptual. The argument is abductive. It draws on philosophical introspection spanning several hundred years, evidence from psychology, and evidence from neuroscience. The argument is that when we look at these three different levels of analysis, the best overall explanation for their results is that perceptual learning occurs, is fairly widespread, and is genuinely perceptual rather than post-perceptual. One key piece of the argument is that neuroscientific perceptual learning experiments repeatedly show that there are changes very early on in the primary sensory cortices after perceptual learning tasks. Coupled with behavioral evidence from psychology and convergent philosophical introspection on the perceptual learning cases, this chapter argues that perceptual learning is genuinely perceptual, rather than post-perceptual.

This chapter argues that when we learn to recognize natural kinds, such as pine trees, this should be understood not in terms of kind properties coming to be represented in our perception, but simply in terms of a shift in our attention, which causes us to represent new low-level properties, such as colors, shapes, and textures. Susanna Siegel has argued that kinds, such as pine trees, can look phenomenally different to someone once that person becomes disposed to recognize them, and that the best explanation for this is that kind properties, such as being a pine tree, can become represented in perception. The chapter details an alternative explanation for the different look of the pine tree: a shift in one’s attentional pattern onto other low-level properties. Philosophers have alluded to this alternative before, but the chapter provides a comprehensive account of the view, drawing on the science of perceptual learning.

This chapter explains memory color as an enhancement of perceptual learning, which enables us to better differentiate objects from their backgrounds. In cases of memory color, faded types of objects with which we associate a prototypical color are sometimes perceived as closer to that color than they actually are. For instance, discolored hearts sometimes appear redder to us than they actually are, and discolored bananas yellower. The goal of this chapter is to understand memory color in terms of perceptual learning. The chapter argues that memory color enhances perceptual learning by enabling us to better differentiate objects from their backgrounds. This account of cases of memory color parts ways with an influential philosophical interpretation of them: that they should be understood as cases of cognitive penetration. It also parts ways with the standard interpretation of memory color cases in psychology: that they should be understood as cases of color constancy.

When a user integrates a sensory substitution device into her life, the process involves perceptual learning, that is, ‘relatively long-lasting changes to an organism’s perceptual system that improve its ability to respond to its environment’. In this chapter, I explore ways in which the extensive literature on perceptual learning can be applied to help improve sensory substitution devices. I then use these findings to answer a philosophical question. Much of the philosophical debate surrounding sensory substitution devices concerns what happens after perceptual learning occurs. In particular, should the resultant perceptual experience be classified in the substituted modality (as vision), in the substituting modality (as auditory or tactile), or in a new sense modality? I propose a novel empirical test to help resolve this philosophical debate.

One limitation of sensory substitution devices (SSDs) is their inability to reproduce the non-sensory feelings that are normally associated with visual experiences, especially hedonic responses. This is sometimes reported to cause SSD users frustration and it is unclear that improvements in acuity, bandwidth, or training will resolve the issue. We offer a novel solution. Researchers can produce hedonic responses by eliciting these feelings artificially, pairing distal objects that should be pleasurable to pleasurable outputs from the SSD. We outline two strategies for accomplishing this: first, by means of a prefixed, hardwired association of distal objects to SSD outputs; and second, by means of a flexible, feedback-based association created by subject-directed matching of distal objects to SSD outputs. We evaluate both strategies, and argue that the feedback-based strategy is more promising. Researchers could use this strategy to help the blind, allowing them to take pleasure in objects they perceive using SSDs.

Introduction and aims The health benefits of reducing excessive alcohol consumption are well-documented and widely accepted, but policies directed to this end are often regarded as damaging to the economy. Previous UK alcohol impact studies typically focus on what are in effect the 'gross' impacts of a fall in alcohol consumption considered in isolation, so that estimated economic impacts are always negative. Here we investigate the 'net' impacts of a reduction in consumption accounting for the reallocation of household spending and the expenditure of any increase in government revenues. Design and methods We employ a health-augmented, Input-Output modelling framework. We simulate the impact of a reduction in alcohol consumption due to: a change in consumer tastes that generate a reallocation of household spending; an increase in alcohol duties accompanied by the use of increased revenues to stimulate government expenditure. Results We find evidence of a trade-off between employment and health benefits for the case of a tastes-induced switch from alcohol consumption, but this is less severe than past analyses would suggest (and does not apply to economic activity more generally). For the case of increased taxation on alcohol (and increased government spending) we find that there is in fact no trade-off between employment on the one hand and health on the other; employment and economic activity are stimulated while health outcomes improve. Discussion and conclusions There is a potential 'double-dividend' of improved health outcomes and increased economic activity as a consequence of a rise in alcohol duties.

Background In Western Europe, currently only Ireland and Portugal continue to provide universal neonatal bacillus Calmette-Guerin (BCG) vaccination programs, despite not being considered as high tuberculosis (TB) incidence countries. Other European countries only vaccinate infants considered at high risk of contracting TB. We evaluated the cost-effectiveness of selective BCG vaccination compared with strategies of universal and no vaccination. Methods An economic model was used to simulate a cohort from birth to life expectancy, taking the perspective of the publicly funded healthcare system. BCG protection was modeled to last 15 years. International vaccine efficacy data were combined with Irish epidemiologic and cost data. The model took into account long-term sequelae associated with TB meningitis and severe adverse reactions relating to the BCG vaccine. A fully probabilistic model was used to incorporate uncertainty across all parameters. Results At O139,557 per quality-adjusted life year, selective vaccination was not cost-effective relative to a program of no vaccination. The incremental cost-effectiveness of universal vaccination was O2.55 million per quality-adjusted life year relative to selective vaccination. There was substantial uncertainty regarding the effectiveness of BCG vaccination. The cost-effectiveness of selective vaccination could be substantially improved by reducing the cost of administering the vaccine. Conclusions In the absence of changes to other aspects of TB control, a switch to selective vaccination will result in increased cases of childhood TB. Although not considered cost-effective, selective vaccination may be preferable to no vaccination until other changes to TB control may be implemented to reduce the risk of TB in children.

Distress tolerance (DT), the perceived or actual ability to tolerate negative emotional or physical states, is inversely related to posttraumatic stress disorder (PTSD) symptoms in civilian, community samples. No studies to date have examined the relationship between DT and PTSD in clinical samples of veterans with a comorbid diagnosis of PTSD and a substance use disorder (SUD). Thus, the present study examined the relationship between DT and PTSD in a sample of predominately African American, male veterans (n = 75) diagnosed with comorbid PTSD and SUD (according to a structured clinical interview). Results of hierarchical linear regression models indicated that DT was inversely related to total PTSD symptom severity score, above and beyond depressive symptoms and SUD severity. Of the 4 symptom clusters, DT was inversely associated with intrusions and hyperarousal. These findings are discussed in light of previous work with civilian samples. Determining whether treatment incorporating DT skills would be useful for veterans undergoing PTSD treatment should be evaluated.

Objective: Macrophages play a role in clearing bacteria from the gut in the initial stages of necrotizing enterocolitis (NEC). Macrophage Inflammatory Protein-1α (MIP-1α), also known as CCL3, is a chemokine produced by macrophages that enhances the immune response. It acts as both a recruiter of immune cells and a coactivator of other macrophages. Interleukin-12 (IL-12) is a pro-inflammatory chemotactant produced by several types of phagocytic cells such as dendritic cells and neutrophils, but primarily by macrophages. We hypothesized that the pro-inflammatory state associated with NEC pathophysiology would induce increased expression of MIP-1α and IL-12 that would be detectable in serum and intestinal tissue. Methods: Timed pregnant Sprague-Dawley rats were randomized by litter. Controls were delivered vaginally and dam-fed. NEC pup groups were delivered 12 h prematurely via Cesarean section, formula fed, given a single oral dose of lipopolysaccharide, and subjected to intermittent cold and hypoxia as part of a proven NEC rat model protocol. Animals were sacrificed at 0, 12, 24, 48, 72, and 96 h of life and serum and intestinal tissue samples were collected. Samples were analysed via western blot using antibodies with affinity to MIP-1α and IL-12 respectively. Results: Serum and ileal levels of MIP-1 alpha were increased from 48 to 72 h in NEC animals when compared with controls. Serum and ileal IL-12 was downregulated in NEC groups at 12 and 24 h compared to controls. Conclusion: Macrophage function plays an important role in the first 48 h of NEC pathophysiology. Downregulation of IL-12 in the setting of increased MIP-1α expression may represent deranged or inhibited macrophage function in the context of NEC pathogenesis. Further work to elucidate the significance of these findings is warranted.

The home environment is an important influence on children’s health and development. We aimed to identify the specific actions, objects, events, and conditions within households that influence child well-being. This cross-sectional study was conducted in Kilifi District among 146 children aged 8–10 years. We derived the Kilifi-Home Inventory for Primary School Children (Kilifi-HIPSC) through the modification and adaption of an existing measure of the home environment. The final 45 items were grouped into subscales comprising items which cohered conceptually. The measure was suitable for both genders and applicable across its intended age range. Nutritional status and household wealth contributed to variance in Kilifi-HIPSC scores. In turn, the home environment was associated with language and motor outcomes in school-age children. The brevity of the measure facilitates quick screening of the promotive aspects of a child’s home environment.

A recent debate in Kant scholarship concerns the role of concepts in Kant's theory of perception. Roughly, proponents of a conceptualist interpretation argue that for Kant, the possession of concepts is a prior condition for perception, while nonconceptualist interpreters deny this. The debate has two parts. One part concerns whether possessing empirical concepts is a prior condition for having empirical intuitions. A second part concerns whether Kant allows empirical intuitions without a priori concepts. Outside of Kant interpretation, the contemporary debate about conceptualism concerns whether perception requires empirical concepts. But, as I argue, the debate about whether Kant allows intuitions without empirical concepts does not show whether Kant is a conceptualist. Even if Kant allows intuitions without empirical concepts, it could still be that a priori concepts are required. While the debate could show that Kant is a conceptualist, I argue it does not. Finally, I sketch a novel way that the conceptualist interpreter might win the debate—roughly, by arguing that possessing a priori concepts is a prior condition for having appearances.

Suppose you have recently gained a disposition for recognizing a high-level kind property, like the property of being a wren. Wrens might look different to you now. According to the Phenomenal Contrast Argument, such cases of perceptual learning show that the contents of perception can include high-level kind properties such as the property of being a wren. I detail an alternative explanation for the different look of the wren: a shift in one’s attentional pattern onto other low-level properties. Philosophers have alluded to this alternative before, but I provide a comprehensive account of the view, show how my account significantly differs from past claims, and offer a novel argument for the view. Finally, I show that my account puts us in a position to provide a new objection to the Phenomenal Contrast Argument.

Today's uncertain economic environment and changing demographics and land use patterns challenge transportation agencies to transform how they do business. Like some of its counterparts throughout the country, the Santa Clara Valley Transportation Authority (VTA) in Northern California has faced these challenges and is leading organizational change. This paper refines the process developed by John Kotter for successful organizational change in the private sector and applies the process to the public transportation industry. Examples from the development of VTA's Express bus business plan show how Kotter's private-sector organizational development concepts can be put into practice by a transportation agency. The paper also identifies the threats to change and opportunities for improvement based on lessons identified during interviews of external stakeholders and VTA staff. By presenting the approach used and the lessons learned, this paper can serve as a reference for transportation professionals whose strategic goal is to lead and implement change successfully within their agencies.

Highlights ► The safety and immunogenicity of one or two doses of a recombinant A (H1N1) 2009 influenza VLP vaccine was evaluated in a two-stage, Phase 2, randomized, double-blind, placebo-controlled study conducted during the H1N1 2009 pandemic in Mexico. ► The H1N1 2009 VLP vaccine was safe and well-tolerated with no vaccine-related serious adverse events. ► The VLP vaccine groups demonstrated robust HAI immune responses after a single vaccination, which were statistically higher compared to placebo., Virus-like particles (VLPs) can be rapidly developed from influenza virus genetic sequences in order to supply vaccine after the onset of a pandemic. The safety and immunogenicity of one or two doses of a recombinant A (H1N1) 2009 influenza VLP vaccine was evaluated in a two-stage, Phase 2, randomized, double-blind, placebo-controlled study conducted in 4563 healthy adults, 18–64 years of age, during the H1N1 2009 pandemic in Mexico. In Part A, 1013 subjects were randomized into four treatment groups (5 μg, 15 μg, or 45 μg hemagglutinin [HA] VLP vaccine or placebo) and vaccinated 21 days apart, with sera collected on Days 1, 14 and 36 for hemagglutination inhibition (HAI) testing. After review of safety and immunogenicity data from Part A, additional subjects were immunized with a single dose of 15 μg VLP vaccine (N = 2537) or placebo (N = 1011) and assessed for safety in Part B. Results showed the H1N1 2009 VLP vaccine was safe and well-tolerated. Systemic solicited events were similar between placebo and VLP vaccinated groups with no vaccine-related serious adverse events. Dose response trends for solicited local adverse events were observed, with higher incidences of local pain, swelling, tenderness, and redness reported in the higher VLP dose groups (15 μg and 45 μg) compared to the placebo and 5 μg VLP groups following both vaccinations. Although the majority of local AEs were mild in severity, a dose trend in events of moderate or greater severity was also noted for these solicited events. The VLP vaccine groups demonstrated robust HAI immune responses after a single vaccination, with high rates of seroprotection (≥40 HAI titer) in 82–92% of all subjects and in 64–85% of subjects who were seronegative at the time of immunization. HAI geometric mean titers (GMTs), geometric mean ratios (GMRs) and seroconversion rates were also all statistically higher in the VLP groups compared to placebo for both post-baseline time points. Based on these data, additional clinical trials are in development to evaluate influenza vaccine candidate antigens manufactured using Spodoptera frugiperda (Sf9)/baculovirus-based VLP technology.

We seem perfectly able to perceive fine-grained shades of colour even without possessing precise concepts for them. The same might be said of shapes. I argue that this is in fact not the case. A subject can perceive a colour or shape only if she possesses a concept of that type of colour or shape. I provide new justification for this thesis, and do not rely on demonstrative concepts such as THIS SHADE or THAT SHAPE, a move first suggested by John McDowell, but rejected by Christopher Peacocke and Richard Heck among others.1

Detection of neutralizing antibody to viral neuraminidase (NA) by testing for enzyme inhibition has been recognized as an important part of the immunogenicity of influenza vaccines. However, the absence of a well characterized standard source of active NA and validated assays has significantly limited clinical studies of NA immunity. Influenza virus-like particles (VLPs) containing hemagglutinin (HA), NA, and M1 proteins were produced from insect cells infected with a recombinant baculovirus and used as the NA source for the NA inhibition (NAI) assay. The NA activity of 6 different VLP strains varied from 0.43 to 1.61 (×10−3) enzyme units per μg of HA and was stable over 6 months of storage at 2–8 °C. The NAI assay using 2′-(4-methylumbelliferyl)-α- d -N-acetylneuraminic acid as a substrate was modified for testing the antibody titer in clinical samples and validated. The advantages of the assay include: (1) stable, reproducible, and standardized source of NA; (2) testing the antibody titer specific to each subtype of NA in serum from subjects immunized with trivalent vaccines (H1N1, H3N2, B) with no interference from antibodies specific to the HA and to heterologous subtypes of the NA; (3) suitability for conducting long-term clinical trials as a result of low intra- and inter-assay variability, and (4) a wide analytical range due to 25% inhibition cut-off value for the NAI titer estimation.

The Santa Clara Valley Transportation Authority in California recently developed a strategic plan for bus rapid transit (BRT) to establish a framework for BRT implementation. Stevens Creek Boulevard, an important east-west thoroughfare linking the California cities of San Jose and Cupertino, was one of three corridors selected for BRT service. To ensure the operating and ridership objectives along the Stevens Creek corridor, BRT must maintain adequate travel speeds and provide a convenient station location along the Valley Fair segment west of downtown San Jose. Meeting these objectives would be a challenge because the segment is highly congested and right-of-way constrained. Major shopping centers, existing land uses, and an Interstate freeway interchange are all factors that contribute to the operational challenges along the Valley Fair segment. These factors also limit any roadway widening and reconfiguration required to provide sufficient space for dedicated BRT lanes and station platforms. To provide some form of transit priority and a convenient BRT station at Valley Fair, a single reversible bus lane was proposed. This paper discusses the feasibility of a single reversible lane and key elements that led to a preferred configuration and operating plan. A range of options, including various station configurations and operating strategies, is evaluated. A microsimulation analysis of the options shows that a single reversible lane can generate significant operating benefits for BRT while not significantly affecting mixed-flow traffic. This paper and its results should encourage cities to consider single-lane reversible bus ways along constrained segments as part of a strategy to implement premium BRT service.

The erbB family of receptor tyrosine kinases are known to play important roles in normal epithelial development and epithelial neoplasia. Considerable evidence also suggests that signaling through the epidermal growth factor receptor (EGFR) plays an important role in multistage skin carcinogenesis in mice; however, less is known about the role of erbB2. In this study, to further examine the role of both erbB2 and EGFR in epithelial carcinogenesis, we examined the effect of a dual erbB2/EGFR tyrosine kinase inhibitor, GW2974, given in the diet on skin tumor promotion during two-stage carcinogenesis in wild-type and BK5.erbB2 mice. In BK5.erbB2 mice, erbB2 is overexpressed in the basal layer of epidermis and leads to heightened sensitivity to skin tumor development. GW2974 effectively inhibited skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in wild-type and BK5.erbB2 mice, although a more marked effect was seen in BK5.erbB2 mice. In addition, this inhibitory effect was reversible when GW2974 treatment was withdrawn. GW2974 inhibited 12-O-tetradecanoylphorbol-13-acetate–induced epidermal hyperproliferation, which correlated with reduced activation of both the EGFR and erbB2. These results support the hypothesis that both the EGFR and erbB2 play an important role in the development of skin tumors during two-stage skin carcinogenesis, especially during the tumor promotion stage. Furthermore, the marked sensitivity of BK5.erbB2 mice to the inhibitory effects of GW2974 during tumor promotion suggest greater efficacy for this compound when erbB2 is overexpressed or amplified as an early event in the carcinogenic process. Cancer Prev Res; 3(8); 940–52. ©2010 AACR.

O desenvolvimento motor é um fenômeno que permeia a vida de todas as pessoas; ele possibilita a realização de atos motores essenciais à lida diária não só por sua excepcional idade, mas também por sua ubiqüidade. De onde vem o nosso entendimento sobre esse fenômeno? O que sabemos hoje sobre ele? Para onde devemos caminhar na busca de novos conhecimentos? Essas são as questões abordadas no presente ensaio