Paul Krugman and the New Economic Geography - assesment in the light of the dynamics of a “real world” local system of firms

Since the publication of Krugman's paper on "Geography and Trade" in 1991, a burgeoning literature has developed under the heading New Economic Geography. In the following we shall survey the NEG literature and critically evaluate its contribution relative to earlier work on similar topics. More specifically, we will focus our attention on a model that seems to have given new impulses to the introduction of spatial factors into the economic analysis: Krugman’s model. We will proceed with our assesment analysing if and to which extent the features of the model are effective in investigating a real local system of firms: the Etna Valley, an industrial agglomeration specialized in the production of microelectronic components in the area around the Sicilian town of Catania. What emerges from the critical analysis is that the above model results to be extremely simplified. If, on one hand this may be true for every economic model, on the other, we feel that, in our specific case study, the formalization of the processes of local development does not result to be entirely useful. Indeed, great part of the analysis of the industrial district based on the “industrial atmosphere” (Marshall, 1890) remains out of the picture. Therefore, we find more useful the positions of those authors that not drawing on the deductive methods of theorising and analysing employed by Krugman, nonetheless have managed to enlighten mechanisms that seem to be more apt to investigate dynamics taking place in developing areas. More specifically, they seem to offer more useful insights in the context of non stationary economies where markets are not yet stabilized and therefore are not entirely capable of adequately transmitting incentives and information to the actors in the economy.

Governance and the Processes of Inclusion/Exclusion: A Review of the Theory and Practice.

Governance identifies a discursive domain(Newman, 2002) in which both the policy and academic debate about new institutional configurations emerging from the proliferation of new forms of governing outside and beyond the state, is taking place My concern here is to highlight what I think is an under-theorised dimension in most of the perspectives from which the new forms of governance beyond the state are analysed. Specifically, I embrace Newman’s (2001) suggestion that most of the literature on Governance suffers from an under-theorisation of a “social†dimension of the analysis or, of what she terms the “politics of the wider public realm and the patterns of inclusion and exclusion on which it is based.†Using the above reflection as analytical starting point, this paper aims at showing how an important challenge for the field of Governance studies resides in the attempt to connect administrative and managerial issues with a broader set of issues concerning the nature of political participation in complex societes where not only the borders of the national states are blurred but the character of individual and collective identities is also relational and fluid. We will proceed first by critically reviewing from this perspective some of the current debates taking place in the Governance literature. Secondly by highlighting the concepts I consider fruitful to problematise the social dimension of the state-citizen relationship and to raise important questions with respect to the inclusionary and exclusionary practices on which it is based. And finally I will address the themes of inclusion and composition of consensus amidst diversity and complexity in the light of New Labour’s approach to Governance and, specifically, of its discourses of social inclusion, democratic renewal, networks and partnership governing.

Transforming sub-national economic governance in England : From competitive regions to competitive city-regions.

This doctoral study is situated within key debates concerned with how new urban and regional spaces are being produced in globalisation. Emphasising the weaknesses of 'orthodox' techno-economic interpretations of the 'rise of the region', the state space approach conceives the emergence of new regional governance spaces as the result of political processes in which the state plays a key role (Brenner, 2004). While this framework highlights the role of existent scalar/institutional arrangements (and their political orientations) in channelling and delimiting political economic change, it also raises crucial questions on the role of agency. There is the need for a more developed understanding of issues of political agency and struggle in particular in relation to the shaping of particular regional governance spaces. This study explores the rescaling of economic governance in England from the early to the mid-2000s through a process of 'central orchestrated regionalisation' involving the creation of new regional and city-regional institutions and supports shaped by tensions between national political objectives and regional and local interests. In particular it considers the establishment and development of these frameworks in the context of a particular region, the Yorkshire and the Humber.The PhD contributes to contemporary research on new regional governance spaces in two key ways. Firstly, it develops an enriched formulation of the state space through the engagement with the complementary notions of a 'politics of scale' (Cox, 1998) and regional 'armatures' (Liepietz, 1994). The value of this reformulation is in its capacity to inspire a type of multi-dimensional and multi-scalar regional research through which empirically rich, theoretically driven accounts of regional (trans-)formation can be developed in order to advance knowledge of state space. Secondly, it provides a more nuanced account of the formation of new geographies of governance in the interplay between inherited and emergent arrangements where the tensions that emerge in this process pertain only in part to the difficulties in absorbing extant local institutional circumstances in the trajectory of emergent state initiatives. Crucially, different governance actors, at different spatial scales, frame these problems in different ways as they attempt to calibrate governance arrangements that can assist them in better pursuing their interests

The characterization of Thermotoga maritima Arginine Binding Protein variants demonstrates that minimal local strains have an important impact on protein stability

The Ramachandran plot is a versatile and valuable tool that provides fundamental information for protein structure determination, prediction, and validation. The structural/thermodynamic effects produced by forcing a residue to adopt a conformation predicted to be forbidden were here explored using Thermotoga maritima Arginine Binding Protein (TmArgBP) as model. Specifically, we mutated TmArgBP Gly52 that assumes a conformation believed to be strictly disallowed for non-Gly residues. Surprisingly, the crystallographic characterization of Gly52Ala TmArgBP indicates that the structural context forces the residue to adopt a non-canonical conformation never observed in any of the high-medium resolution PDB structures. Interestingly, the inspection of this high resolution structure demonstrates that only minor alterations occur. Nevertheless, experiments indicate that Gly52 replacements in TmArgBP produce destabilizations comparable to those observed upon protein truncation or dissection in domains. Notably, we show that force-fields commonly used in computational biology do not reproduce this non-canonical state. Using TmArgBP as model system we here demonstrate that the structural context may force residues to adopt conformations believed to be strictly forbidden and that barely detectable alterations produce major destabilizations. Present findings highlight the role of subtle strains in governing protein stability. A full understanding of these phenomena is essential for an exhaustive comprehension of the factors regulating protein structures

GINGER

In this paper, we outline the scientific objectives, the experimental layout, and the collaborations envisaged for the GINGER (Gyroscopes IN GEneral Relativity) project. The GINGER project brings together different scientific disciplines aiming at building an array of Ring Laser Gyroscopes (RLGs), exploiting the Sagnac effect, to measure continuously, with sensitivity better than picorad/ s, large bandwidth (ca. 1 kHz), and high dynamic range, the absolute angular rotation rate of the Earth. In the paper, we address the feasibility of the apparatus with respect to the ambitious specifications above, as well as prove how such an apparatus, which will be able to detect strong Earthquakes, very weak geodetic signals, as well as general relativity effects like Lense-Thirring and De Sitter, will help scientific advancements in Theoretical Physics, Geophysics, and Geodesy, among other scientific fields.Comment: 21 pages, 9 figure

DECLINE OF PREVALENCE OF RESISTANCE ASSOCIATED SUBSTITUTIONS TO NS3 AND NS5A INHIBITORS AT DAA- FAILURE IN HEPATITIS C VIRUS IN ITALY OVER THE YEARS 2015 TO 2018

Background: A minority of patients fails to eliminate HCV and resistance-associated substitutions (RASs) are commonly detected at failure of interferon-free DAA regimens . Methods: Within the Italian network VIRONET-C, the prevalence of NS3/NS5A/NS5B RASs was retrospectively evaluated in patients who failed an EASL recommended DAA-regimen in 2015-2018 . The geno2pheno system and Sorbo MC et al. Drug Resistance Updates 2018 were used to infer HCV- genotype/subtype and predict drug resistance . The changes in prevalence of RASs over time were evaluated by chi-square test for trend, predictors of RASs at failure were analysed by logistic regression . Results: We included 386 HCV infected patients: 75% males, median age was 56 years (IQR 52-61), metavir fibrosis stage F4 in 76%; 106 (28%) were treatment- experienced: 91 (86%) with IFN-based treatments, 26 (25%) with DAAs. Patients with HIV and HBV coinfection were 10% (33/317) and 8% (6/72), respectively. HCV genotype was 1b in 122 pts (32%), 3 in 109 (28%), 1a in 97 (25%), 4 in 37 (10%), 2 in 21 (5%). DAA regimens were: LDV/SOF in 115 (30%), DCV/SOF in 103 (27%), 3D in 83 (21%), EBR/GRZ in 32 (8%), VEL/SOF in 29 (7%), GLE/PIB in 18 (5%) and 2D in 6 (2%); ribavirin was administered in 123 (32%) . The NS5A fasta-sequence was available for all patients, NS5B for 361 (94%), NS3 for 365 (95%) . According to the DAA failed the prevalence of any RASs was 90%, namely 80/135 (59%) in NS3, 313/359 (87%) in NS5A, 114/286 (40%) in NS5B . The prevalence of any RASs significantly declined from 2015 to 2018 (93% vs 70%, p=0.004): NS5A RASs from 90% to 72% (p=0 .29), NS3 RASs from 74% to 18% (p<0 .001), while NS5B RASs remained stable . Independent predictors of any RASs included advanced fibrosis (AOR 6.1, CI 95% 1.8-20.3, p=0 .004) and genotype (G2 vs G1a AOR 0 .03, CI 95% 0 .002- 0 .31, p=0 .004; G3 vs G1a AOR 0 .08, CI 95% 0 .01-0 .62, p=0 .02; G4 vs G1a AOR 0 .05, CI 95% 0 .006-0 .46, p=0 .008), after adjusting for age, previous HCV treatment and year of genotype . Notably, full activity was predicted for GLE/PIB in 75% of cases and for at least two components of VEL/SOF/VOX in 53% of cases, no case with full-resistance to either regimen was found . Conclusion: Despite decreasing prevalence over the years, RASs remain common at virological failure of DAA treatment, particularly in patients with the highest grade of liver fibrosis. The identification of RASs after failure could play a crucial role in optimizing retreatment strategies

Epithelial ovarian cancer is infiltrated by activated effector T cells co-expressing CD39, PD-1, TIM-3, CD137 and interacting with cancer cells and myeloid cells

IntroductionDespite predicted efficacy, immunotherapy in epithelial ovarian cancer (EOC) has limited clinical benefit and the prognosis of patients remains poor. There is thus a strong need for better identifying local immune dynamics and immune-suppressive pathways limiting T-cell mediated anti-tumor immunity.MethodsIn this observational study we analyzed by immunohistochemistry, gene expression profiling and flow cytometry the antigenic landscape and immune composition of 48 EOC specimens, with a focus on tumor-infiltrating lymphocytes (TILs).ResultsActivated T cells showing features of partial exhaustion with a CD137+CD39+PD-1+TIM-3+CD45RA-CD62L-CD95+ surface profile were exclusively present in EOC specimens but not in corresponding peripheral blood or ascitic fluid, indicating that the tumor microenvironment might sustain this peculiar phenotype. Interestingly, while neoplastic cells expressed several tumor-associated antigens possibly able to stimulate tumor-specific TILs, macrophages provided both co-stimulatory and inhibitory signals and were more abundant in TILs-enriched specimens harboring the CD137+CD39+PD-1+TIM-3+CD45RA-CD62L-CD95+ signature.ConclusionThese data demonstrate that EOC is enriched in CD137+CD39+PD-1+TIM-3+CD45RA-CD62L-CD95+ T lymphocytes, a phenotype possibly modulated by antigen recognition on neoplastic cells and by a combination of inhibitory and co-stimulatory signals largely provided by infiltrating myeloid cells. Furthermore, we have identified immunosuppressive pathways potentially hampering local immunity which might be targeted by immunotherapeutic approaches

Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting: evidence from the REPOSI Register

Diabetes is an increasing global health burden with the highest prevalence (24.0%) observed in elderly people. Older diabetic adults have a greater risk of hospitalization and several geriatric syndromes than older nondiabetic adults. For these conditions, special care is required in prescribing therapies including anti- diabetes drugs. Aim of this study was to evaluate the appropriateness and the adherence to safety recommendations in the prescriptions of glucose-lowering drugs in hospitalized elderly patients with diabetes. Data for this cross-sectional study were obtained from the REgistro POliterapie-Società Italiana Medicina Interna (REPOSI) that collected clinical information on patients aged ≥ 65 years acutely admitted to Italian internal medicine and geriatric non-intensive care units (ICU) from 2010 up to 2019. Prescription appropriateness was assessed according to the 2019 AGS Beers Criteria and anti-diabetes drug data sheets.Among 5349 patients, 1624 (30.3%) had diagnosis of type 2 diabetes. At admission, 37.7% of diabetic patients received treatment with metformin, 37.3% insulin therapy, 16.4% sulfonylureas, and 11.4% glinides. Surprisingly, only 3.1% of diabetic patients were treated with new classes of anti- diabetes drugs. According to prescription criteria, at admission 15.4% of patients treated with metformin and 2.6% with sulfonylureas received inappropriately these treatments. At discharge, the inappropriateness of metformin therapy decreased (10.2%, P < 0.0001). According to Beers criteria, the inappropriate prescriptions of sulfonylureas raised to 29% both at admission and at discharge. This study shows a poor adherence to current guidelines on diabetes management in hospitalized elderly people with a high prevalence of inappropriate use of sulfonylureas according to the Beers criteria