FROM GIBRAT'S LEGACY TO GIBRAT'S FALLACY. A BAYESIAN APPROACH TO STUDY THE GROWTH OF FIRMS

We aim at testing Gibrat's Law, a building block of the corporate growth dynamics. Using a Bayesian statistical framework that nests previous approaches, we provide evidence against Gibrat's law on average, within or across industries. Notwithstanding, data show only weak evidence of mean reversion, i.e. initial larger firms do not grow relatively slower than smaller firms. Moreover, differences in growth rates and in size steady state are persistent and firm-specific. Previous results confirming Gibrat's argument are likely to be incorrect being based on models that do not exploit appropriately all information contained in a panel data set.Gibrat's Law; Panel Data; Heterogeneity; Bayesian Estimation

Inotuzumab Ozogamicin Murine Analog–Mediated B-Cell Depletion Reduces Anti-islet Allo- and Autoimmune Responses

B cells participate in the priming of the allo- and autoimmune responses, and their depletion can thus be advantageous for islet transplantation. Herein, we provide an extensive study of the effect of B-cell depletion in murine models of islet transplantation. Islet transplantation was performed in hyperglycemic B-cell–deficient(μMT) mice, in a purely alloimmune setting (BALB/c into hyperglycemic C57BL/6), in a purely autoimmune setting (NOD.SCID into hyperglycemic NOD), and in a mixed allo-/autoimmune setting (BALB/c into hyperglycemic NOD). Inotuzumab ozogamicin murine analog (anti-CD22 monoclonal antibody conjugated with calicheamicin [anti-CD22/cal]) efficiently depleted B cells in all three models of islet transplantation examined. Islet graft survival was significantly prolonged in B-cell–depleted mice compared with control groups in transplants of islets from BALB/c into C57BL/6 (mean survival time [MST]: 16.5 vs. 12.0 days; P = 0.004), from NOD.SCID into NOD (MST: 23.5 vs. 14.0 days; P = 0.03), and from BALB/c into NOD (MST: 12.0 vs. 5.5 days; P = 0.003). In the BALB/c into B-cell–deficient mice model, islet survival was prolonged as well (MST: μMT = 32.5 vs. WT = 14 days; P = 0.002). Pathology revealed reduced CD3+ cell islet infiltration and confirmed the absence of B cells in treated mice. Mechanistically, effector T cells were reduced in number, concomitant with a peripheral Th2 profile skewing and ex vivo recipient hyporesponsiveness toward donor-derived antigen as well as islet autoantigens. Finally, an anti-CD22/cal and CTLA4-Ig–based combination therapy displayed remarkable prolongation of graft survival in the stringent model of islet transplantation (BALB/c into NOD). Anti-CD22/cal–mediated B-cell depletion promotes the reduction of the anti-islet immune response in various models of islet transplantation

Global and Regional IUCN Red List Assessments: 1

In this contribution, the conservation status assessment of six plant species according to IUCN categories and criteria are presented. It includes the assessment at global level of Linaria tonzigii Lona, Allium garganicum Brullo, Pavone, Salmeri & Terrasi, Ferula arrigonii Bocchieri, Orchis patens Desf. subsp. patens and Armeria saviana Selvi and the assessment at regional level (Italy) of Viola jordanii Hanry

A Novel Clinically Relevant Strategy to Abrogate Autoimmunity and Regulate Alloimmunity in NOD Mice

OBJECTIVE - To investigate a new clinically relevant immunoregulatory strategy based on treatment with murine Thymoglobulin mATG Genzyme and CTLA4-Ig in NOD mice to prevent alloand autoimmune activation using a stringent model of islet transplantation and diabetes reversal. RESEARCH DESIGN AND METHODS - Using allogeneic islet transplantation models as well as NOD mice with recent onset type 1 diabetes, we addressed the therapeutic efficacy and immunomodulatory mechanisms associated with a new immunoregulatory protocol based on prolonged low-dose mATG plus CTLA4-Ig. RESULTS - BALB/c islets transplanted into hyperglycemic NOD mice under prolonged mATG+CTLA4-Ig treatment showed a pronounced delay in allograft rejection compared with untreated mice (mean survival time: 54 vs. 8 days, P < 0.0001). Immunologic analysis of mice receiving transplants revealed a complete abrogation of autoimmune responses and severe downregulation of alloimmunity in response to treatment. The striking effect on autoimmunity was confirmed by 100% diabetes reversal in newly hyperglycemic NOD mice and 100% indefinite survival of syngeneic islet transplantation (NOD.SCID into NOD mice). CONCLUSIONS - The capacity to regulate alloimmunity and to abrogate the autoimmune response in NOD mice in different settings confirmed that prolonged mATG+CTLA4-Ig treatment is a clinically relevant strategy to translate to humans with type 1 diabetes

Proteomics Reveals Novel Oxidative and Glycolytic Mechanisms in Type 1 Diabetic Patients' Skin Which Are Normalized by Kidney-Pancreas Transplantation

Background: In type 1 diabetes (T1D) vascular complications such as accelerated atherosclerosis and diffused macro-/microangiopathy are linked to chronic hyperglycemia with a mechanism that is not yet well understood. End-stage renal disease (ESRD) worsens most diabetic complications, particularly, the risk of morbidity and mortality from cardiovascular disease is increased several fold. Methods and Findings: We evaluated protein regulation and expression in skin biopsies obtained from T1D patients with and without ESRD, to identify pathways of persistent cellular changes linked to diabetic vascular disease. We therefore examined pathways that may be normalized by restoration of normoglycemia with kidney-pancreas (KP) transplantation. Using proteomic and ultrastructural approaches, multiple alterations in the expression of proteins involved in oxidative stress (catalase, superoxide dismutase 1, Hsp27, Hsp60, ATP synthase δ chain, and flavin reductase), aerobic and anaerobic glycolysis (ACBP, pyruvate kinase muscle isozyme, and phosphoglycerate kinase 1), and intracellular signaling (stratifin-14-3-3, S100-calcyclin, cathepsin, and PPI rotamase) as well as endothelial vascular abnormalities were identified in T1D and T1D+ESRD patients. These abnormalities were reversed after KP transplant. Increased plasma levels of malondialdehyde were observed in T1D and T1D+ESRD patients, confirming increased oxidative stress which was normalized after KP transplant. Conclusions: Our data suggests persistent cellular changes of anti-oxidative machinery and of aerobic/anaerobic glycolysis are present in T1D and T1D+ESRD patients, and these abnormalities may play a key role in the pathogenesis of hyperglycemia-related vascular complications. Restoration of normoglycemia and removal of uremia with KP transplant can correct these abnormalities. Some of these identified pathways may become potential therapeutic targets for a new generation of drugs

Plant–environment interactions through a functional traits perspective: a review of Italian studies

Italy is among the European countries with the greatest plant diversity due to both a great environmental heterogeneity and a long history of man–environment interactions. Trait-based approaches to ecological studies have developed greatly over recent decades worldwide, although several issues concerning the relationships between plant functional traits and the environment still lack sufficient empirical evaluation. To draw insights on the association between plant functional traits and direct and indirect human and natural pressures on the environmental drivers, this article summarizes the existing knowledge on this topic by reviewing the results of studies performed in Italy adopting a functional trait approach on vascular plants, bryophytes and lichens. Although we recorded trait measurements for 1418 taxa, our review highlighted some major gaps in plant traits knowledge: Mediterranean ecosystems are poorly represented; traits related to belowground organs are still overlooked; traits measurements for bryophytes and lichens are lacking. Finally, intraspecific variation has been little studied at community level so far. We conclude by highlighting the need for approaches evaluating trait–environment relationship at large spatial and temporal scales and the need of a more effective contribution to online databases to tie more firmly Italian researchers to international scientific networks on plant traits

\u201cL\u2019autorecupero: uno strumento a regia pubblica, ad alcune condizioni\u201d

Dalle esperienze avviate nel nostro paese emergono utili spunti per una riflessione sugli impatti concreti che le pratiche di autorecupero possono avere sulla costruzione di politiche pubbliche orientate alla manutenzione del patrimonio ERP sfitto. Molte sono le difficolt\ue0 \u2013 di natura economica e finanziaria, temporale e gestionale, di investimento e commitment \u2013 che si oppongono alla costruzione di condizioni propizie a un loro impiego estensivo. Non meno appaiono per\uf2 le opportunit\ue0 offerte all\u2019innovazione di processi e procedure. Pur trattandosi di operazioni \u2018di nicchia\u2019 fortemente selettive nei confronti di domande sociali e patrimoni spaziali, i percorsi di autorecupero fertilmente sollecitano l\u2019attore pubblico a ricalibrare il proprio ruolo: tra regia e governance di percorsi complessi, e apertura alle molte risorse e competenze di inquilini e terzo settore

"Recuperare il patrimonio abitativo pubblico con gli inquilini"

Uno dei maggiori problemi che gli enti proprietari e gestori del patrimonio di edilizia residenziale pubblica si trovano oggi ad affrontare riguarda il recupero e la riassegnazione degli alloggi sfitti. A fronte di una forte crescita della domanda sociale di abitazioni in locazione, la contrazione della capacit\ue0 di spesa pubblica in interventi di manutenzione sta generando un progressivo aumento del patrimonio ERP inutilizzato. Per aiutare a superare questo impasse, negli ultimi anni, l\u2019avvio di processi di autorecupero da parte degli inquilini \ue8 stato ricorrentemente indicato come una possibile soluzione. Significativa appare tuttavia l\u2019incongruenza tra l\u2019ampiezza del dibattito pubblico e politico sul tema, e l\u2019esiguit\ue0 di pratiche di autorecupero giunte a effettiva conclusione. Il servizio restituisce alcune di tali esperienze, per interrogarsi sulle loro concrete condizioni di efficacia e replicabilit\ue0 per le politiche residenziali pubbliche

L'autorecupero: uno strumento a regia pubblica, ad alcune condizioni

Dalle esperienze avviate nel nostro paese emergono utili spunti per una riflessione sugli impatti concreti che le pratiche di autorecupero possono avere sulla costruzione di politiche pubbliche orientate alla manutenzione del patrimonio ERP sfitto. Molte sono le difficoltà – di natura economica e finanziaria, temporale e gestionale, di investimento e commitment – che si oppongono alla costruzione di condizioni propizie a un loro impiego estensivo. Non meno appaiono però le opportunità offerte all’innovazione di processi e procedure pubbliche. Pur trattandosi di operazioni ‘di nicchia’ fortemente selettive nei confronti di domande sociali e patrimoni spaziali, i percorsi di autorecupero fertilmente sollecitano l’attore pubblico a ricalibrare il proprio ruolo: tra regia e governance di percorsi complessi, e apertura alle molte risorse e competenze di inquilini e terzo settore