Tackling concentrated worklessness: integrating governance and policy across and within spatial scales

Spatial concentrations of worklessness remained a key characteristic of labour markets in advanced industrial economies, even during the period of decline in aggregate levels of unemployment and economic inactivity evident from the late 1990s to the economic downturn in 2008. The failure of certain localities to benefit from wider improvements in regional and national labour markets points to a lack of effectiveness in adopted policy approaches, not least in relation to the governance arrangements and policy delivery mechanisms that seek to integrate residents of deprived areas into wider local labour markets. Through analysis of practice in the British context, we explore the difficulties of integrating economic and social policy agendas within and across spatial scales to tackle problems of concentrated worklessness. We present analysis of a number of selected case studies aimed at reducing localised worklessness and identify the possibilities and constraints for effective action given existing governance arrangements and policy priorities to promote economic competitiveness and inclusion

Stability of Maleimide-PEG and Mono-Sulfone-PEG Conjugation to a Novel Engineered Cysteine in the Human Hemoglobin Alpha Subunit

In order to use a Hemoglobin Based Oxygen Carrier as an oxygen therapeutic or blood substitute, it is necessary to increase the size of the hemoglobin molecule to prevent rapid renal clearance. A common method uses maleimide PEGylation of sulfhydryls created by the reaction of 2-iminothiolane at surface lysines. However, this creates highly heterogenous mixtures of molecules. We recently engineered a hemoglobin with a single novel, reactive cysteine residue on the surface of the alpha subunit creating a single PEGylation site (βCys93Ala/αAla19Cys). This enabled homogenous PEGylation by maleimide-PEG with >80% efficiency and no discernible effect on protein function. However, maleimide-PEG adducts are subject to deconjugation via retro-Michael reactions and cross-conjugation to endogenous thiol species in vivo. We therefore compared our maleimide-PEG adduct with one created using a mono-sulfone-PEG less susceptible to deconjugation. Mono-sulfone-PEG underwent reaction at αAla19Cys hemoglobin with > 80% efficiency, although some side reactions were observed at higher PEG:hemoglobin ratios; the adduct bound oxygen with similar affinity and cooperativity as wild type hemoglobin. When directly compared to maleimide-PEG, the mono-sulfone-PEG adduct was significantly more stable when incubated at 37°C for seven days in the presence of 1 mM reduced glutathione. Hemoglobin treated with mono-sulfone-PEG retained > 90% of its conjugation, whereas for maleimide-PEG < 70% of the maleimide-PEG conjugate remained intact. Although maleimide-PEGylation is certainly stable enough for acute therapeutic use as an oxygen therapeutic, for pharmaceuticals intended for longer vascular retention (weeks-months), reagents such as mono-sulfone-PEG may be more appropriate

Engineering hemoglobin to enable homogenous PEGylation without modifying protein functionality

In order to infuse hemoglobin into the vasculature as an oxygen therapeutic or blood substitute, it is necessary to increase the size of the molecule to enhance vascular retention. This aim can be achieved by PEGylation. However, using non-specific conjugation methods creates heterogenous mixtures and alters protein function. Site-specific PEGylation at the naturally reactive thiol on human hemoglobin (βCys93) alters hemoglobin oxygen binding affinity and increases its autooxidation rate. In order to avoid this issue, new reactive thiol residues were therefore engineered at sites distant to the heme group and the α/β dimer/dimer interface. The two mutants were βCys93Ala/αAla19Cys and βCys93Ala/βAla13Cys. Gel electrophoresis, size exclusion chromatography and mass spectrometry revealed efficient PEGylation at both αAla19Cys and βAla13Cys, with over 80% of the thiols PEGylated in the case of αAla19Cys. For both mutants there was no significant effect on the oxygen affinity or the cooperativity of oxygen binding. PEGylation at αAla19Cys had the additional benefit of decreasing the rates of autoxidation and heme release, properties that have been considered contributory factors to the adverse clinical side effects exhibited by previous hemoglobin based oxygen carriers. PEGylation at αAla19Cys may therefore be a useful component of future clinical products

The Politics of Evidence Use in Health Policy Making in Germany-the Case of Regulating Hospital Minimum Volumes.

This article examines the role of scientific evidence in informing health policy decisions in Germany, using minimum volumes policy as a case study. It argues that scientific evidence was used strategically at various stages of the policy process both by individual corporatist actors and by the Federal Joint Committee as the regulator. Minimum volumes regulation was inspired by scientific evidence suggesting a positive relationship between service volume and patient outcomes for complex surgical interventions. Federal legislation was introduced in 2002 to delegate the selection of services and the setting of volumes to corporatist decision makers. Yet, despite being represented in the Federal Joint Committee, hospitals affected by its decisions took the Committee to court to seek legal redress and prevent policy implementation. Evidence has been key to support, and challenge, decisions about minimum volumes, including in court. The analysis of the role of scientific evidence in minimum volumes regulation in Germany highlights the dynamic relationship between evidence use and the political and institutional context of health policy making, which in this case is characterized by the legislative nature of policy making, corporatism, and the role of the judiciary in reviewing policy decisions

Super diversity and city branding: Rotterdam in perspective

As many other cities around the world, Rotterdam has been investing in improving its image to stimulate urban development and to attract visitors, residents and investors. In particular, during the last 15 years the municipality of Rotterdam has intensified its attempts to develop a ‘brand’ that fits the ‘new Rotterdam’, which was gradually rebuilt after destructive bombardments during the Second World War (Riezebos 2014). In 2014 Rotterdam was ranked 8th by ‘Rough Guide’ in the list of ‘Top 10 Cities to See’, whereas the ‘New York Times’ listed Rotterdam in the top 10 of 52 Places to Go. These rankings demonstrate Rotterdam’s success in repositioning itself, using the physical interior of the city as a key element in its branding strategy.</p

Studying Public Health Law::Principles, Politics, and Populations as Patients

Public health law is firmly establishing itself as a crucial area of scholarly inquiry. Its vital importance has been sharply underscored following the outbreak of COVID-19, in response to which we have seen the institution of extreme legal measures—suchas the UK’s Coronavirus Act 2020—in efforts to control and contain the spread ofthe disease. The pandemic has also starkly exposed the complex nature of the regulatory challenges, nationally, internationally, and globally, to which such public health problems give rise. In approaching these, and other questions concerning the public’s health, such as non-communicable disease, public health law, as a field, brings notable distinctive features: these include a practical focus on populations, institutions, the prevention of ill health, protection of good health, and thepromotion of positive states of well-being; and concomitant critical approaches rooted in theories of social justice as contrasted with more narrow biomedical ethics. Such features make it in some senses atypical territory within the field of health law. Furthermore, the inherent role of political institutions places law conceptually within public health in a way that may be seen as distinguishable from law’s relationship with clinical medicine. This chapter explains how the broad reach and distinct features of public health require a commensurately broad approach to conceptualising public health law, and how distinct practical and theoretical features may be integrated into academic public health law. It also shows how public health law, with its distinct conceptualisations concerning ‘the body’ of medical jurisprudence, can both challenge and enrich medico-legal studies, and bring important perspectives within the broader field of health law

Color adjectives, standards, and thresholds: an experimental investigation

Are color adjectives (“red”, “green”, etc.) relative adjectives or absolute adjectives? Existing theories of the meaning of color adjectives attempt to answer that question using informal (“armchair”) judgments. The informal judgments of theorists conflict: it has been proposed that color adjectives are absolute with standards anchored at the minimum degree on the scale, that they are absolute but have near- midpoint standards, and that they are relative. In this paper we report two experiments, one based on entailment patterns and one based on presupposition accommodation, that investigate the meaning of scalar adjectives. We find evidence confirming the existence of subgroups of the population who operate with different standards for color adjectives. The evidence of interpersonal variation in where standards are located on the relevant scale and how those standards can be adjusted indicates that the existing theories of the meaning of color adjectives are at best only partially correct. We also find evidence that paradigmatic relative adjectives (“tall”, “wide”) behave in ways that are not predicted by the standard theory of scalar adjectives. We discuss several different possible explanations for this unexpected behavior. We conclude by discussing the relevance of our findings for philosophical debates about the nature and extent of semantically encoded context sensitivity in which color adjectives have played a key role

Review of the Palaearctic species of Ismaridae Thomson, 1858 (Hymenoptera: Diaprioidea)

This is an open access article, available to all readers online, published under a Creative Commons BY-NC-ND license: https://creativecommons.org/licenses/by-nc-nd/3.0/. The attached file is the published version of the article

The impact of generation Y’s customer experience on emotions: online banking sector

Recently, banking sector focused on attracting Generation Y (individuals born between 1980 and 2000) because they have emerged as a huge force with growing spending power which will unavoidably rival with Baby Boomers’ market dominance. They try to attract them through a unique customer experience, especially the ability of differentiation. Using the Mehrabian & Russell’s model of stimulus (S) - organism (O) - response (R), this study developed the Generation Y customer experience framework that intends to explain their consumer emotional responses toward customer experience attributes in a bank through three aspects: pleasure, dominance, and arousal toward online banks. Empirical evidence, based on data from a survey suggests that the overall customer experience attributes in the bank had a positive relation with emotional responses in different ways. “Value for money”, “Getting things right the first time” and “Put the consumer first” emerged as the most important attributes for Generation Y in experiencing a bank.info:eu-repo/semantics/acceptedVersio