Developing Territorial Identity: The Experience of Historical Italian Companies

This study aims to contribute to the development of the knowledge on intangibles management by analysing the territorial identity concept from a strategic competitiveness perspective. The purpose of this study is especially to clarify the territorial identity concept by exploring and highlighting its dimensions and determinants. This study considers the perspective of two historical Italian companies that have long been embedded in their territory. By integrating a literature analysis with well-documented case studies, this paper proposes a conceptual framework to capture and explain what companies can develop at the local level in order to improve territorial identity

The zinc finger transcription factor PW1/PEG3 restrains murine beta cell cycling

Aims/hypothesis: Pw1 or paternally-expressed gene 3 (Peg3) encodes a zinc finger transcription factor that is widely expressed during mouse embryonic development and later restricted to multiple somatic stem cell lineages in the adult. The aim of the present study was to define Pw1 expression in the embryonic and adult pancreas and investigate its role in the beta cell cycle in Pw1 wild-type and mutant mice. Methods: We analysed PW1 expression by immunohistochemistry in pancreas of nonpregant and pregnant mice and following injury by partial duct ligation. Its role in the beta cell cycle was studied in vivo using a novel conditional knockout mouse and in vitro by lentivirus-mediated gene knockdown. Results: We showed that PW1 is expressed in early pancreatic progenitors at E9.5 but becomes progressively restricted to fully differentiated beta cells as they become established after birth and withdraw from the cell cycle. Notably, PW1 expression declines when beta cells are induced to proliferate and loss of PW1 function activates the beta cell cycle. Conclusions/interpretation: These results indicate that PW1 is a co-regulator of the beta cell cycle and can thus be considered a novel therapeutic target in diabetes

Unexpected interfarm transmission dynamics during a highly pathogenic avian influenza epidemic

Next-generation sequencing technology is now being increasingly applied to study the within- and between-host population dynamics of viruses. However, information on avian influenza virus evolution and transmission during a naturally occurring epidemic is still limited. Here, we use deep-sequencing data obtained from clinical samples collected from five industrial holdings and a backyard farm infected during the 2013 highly pathogenic avian influenza (HPAI) H7N7 epidemic in Italy to unravel (i) the epidemic virus population diversity, (ii) the evolution of virus pathogenicity, and (iii) the pathways of viral transmission between different holdings and sheds. We show a high level of genetic diversity of the HPAI H7N7 viruses within a single farm as a consequence of separate bottlenecks and founder effects. In particular, we identified the cocirculation in the index case of two viral strains showing a different insertion at the hemagglutinin cleavage site, as well as nine nucleotide differences at the consensus level and 92 minority variants. To assess interfarm transmission, we combined epidemiological and genetic data and identified the index case as the major source of the virus, suggesting the spread of different viral haplotypes from the index farm to the other industrial holdings, probably at different time points. Our results revealed interfarm transmission dynamics that the epidemiological data alone could not unravel and demonstrated that delay in the disease detection and stamping out was the major cause of the emergence and the spread of the HPAI strain

Evidence gaps on weight gain in people living with HIV: a scoping review to define a research agenda

Background: Combined antiretroviral therapy (cART) dramatically improved survival in people living with HIV (PLWH) but is associated with weight gain (WG), raising concern for a possible obesity epidemic in PLWH. This scoping review aims to identify the gaps in the existing evidence on WG in PLWH and generate a future research agenda. Methods: This review was conducted according to the methodology for scoping studies and reported according to the PRISMA Extension for Scoping Review checklist. Articles published in English in the last 10 years indexed in Pubmed, WHO Global Index Medicus, or Embase were searched using specific queries focused on WG in PLWH. Results: Following the selection process, 175 included articles were reviewed to search for the available evidence on four specific topics: (I) definition of WG in PLWH, (II) pathogenesis of WG in PLWH, (III) impact of ART on WG, (IV) correlation of WG with clinical outcomes. A summary of the data enabled us to identify gaps and clearly define the following research agenda: (I) develop a data-driven definition of WG in PLWH and define noninvasive assessment methods for body weight and fat composition; (II) further investigate the interaction between HIV/cART and immunity, metabolism, and adipose tissue; (III) establish the specific role of individual drugs on WG; (IV) clarify the independent role of WG, cART, HIV, and metabolic factors on clinical events. Conclusions: The proposed research agenda may help define future research and fill the knowledge gaps that have emerged from this review

Efficacy of 1998 <i>vs</i> 2006 first-line antiretroviral regimens for HIV infection: an ordinary clinics retrospective investigation

Purpose: The evidence suggesting increased HAART efficacy over time comes from randomized trials or cohort studies. This retrospective multicenter survey aimed to assess the variation over time in the efficacy and tolerability of first-line HAART regimens in unselected patients treated in ordinary clinical settings. Methods: Retrospective analysis of data of all patients starting first-line HAART regimens in 1998 and 2006 at adhering centers in the Italian CISAI group. Results: For the 543 patients included, mean age was 39.1 ± 9.8y in 1998 and 41.0 ± 10.7y in 2006 (p=0.03), with a similar proportion of males. Baseline mean log10 HIV-RNA was 4.56 ± 0.97 copies/mL in 1998 vs 4.91 ± 0.96 copies/mL in 2006 (p&lt;0.001); baseline mean CD4 T-cell counts were 343 ± 314/mm3 in 1998 vs 244 ± 174/mm3 in 2006 (p&lt;0.001). The following outcomes were significantly improved at 48w in 2006: proportion with undetectable HIV-RNA (86.3% vs 58.0%; p&lt;0.001); mean increase in CD4 T-cells count (252 ± 225 vs 173 ± 246; p&lt;0.001); HAART modification (20.1% vs 29.2%; p=0.02); HAART interruption (7.3% vs 14.6%; p=0.01); proportion reporting optimal adherence (92.2% vs 82.7%, p=0.03). No differences were observed in the prevalence of grade 3-4 WHO toxicities (26.4% vs 26.6%; p=0.9). Multivariate logistic regression showed that being treated in 1998 remained an independent predictor of virological failure after several adjustments, including adherence. Conclusions: Our data from patients not included in clinical trials or cohort studies provide an additional line of evidence that the effectiveness of HAART significantly improved in 2006. Treated patients, however, were significantly older and more frequently late HIV presenters in 2006 than in 1998.</br

Prolonged higher dose methylprednisolone vs. conventional dexamethasone in COVID-19 pneumonia: a randomised controlled trial (MEDEAS)

Background: Dysregulated systemic inflammation is the primary driver of mortality in severe coronavirus disease 2019 (COVID-19) pneumonia. Current guidelines favour a 7-10-day course of any glucocorticoid equivalent to dexamethasone 6 mg daily. A comparative randomised controlled trial (RCT) with a higher dose and a longer duration of intervention was lacking. Methods: We conducted a multicentre, open-label RCT to investigate methylprednisolone 80 mg as a continuous daily infusion for 8 days followed by slow tapering versus dexamethasone 6 mg once daily for up to 10 days in adult patients with COVID-19 pneumonia requiring oxygen or noninvasive respiratory support. The primary outcome was reduction in 28-day mortality. Secondary outcomes were mechanical ventilation-free days at 28 days, need for intensive care unit (ICU) referral, length of hospitalisation, need for tracheostomy, and changes in C-reactive protein (CRP) levels, arterial oxygen tension/inspiratory oxygen fraction (P aO2 /F IO2 ) ratio and World Health Organization Clinical Progression Scale at days 3, 7 and 14. Results: 677 randomised patients were included. Findings are reported as methylprednisolone (n=337) versus dexamethasone (n=340). By day 28, there were no significant differences in mortality (35 (10.4%) versus 41 (12.1%); p=0.49) nor in median mechanical ventilation-free days (median (interquartile range (IQR)) 23 (14) versus 24 (16) days; p=0.49). ICU referral was necessary in 41 (12.2%) versus 45 (13.2%) (p=0.68) and tracheostomy in 8 (2.4%) versus 9 (2.6%) (p=0.82). Survivors in the methylprednisolone group required a longer median (IQR) hospitalisation (15 (11) versus 14 (11) days; p=0.005) and experienced an improvement in CRP levels, but not in P aO2 /F IO2 ratio, at days 7 and 14. There were no differences in disease progression at the prespecified time-points. Conclusion: Prolonged, higher dose methylprednisolone did not reduce mortality at 28 days compared with conventional dexamethasone in COVID-19 pneumonia

Defining the identity and the niches of epithelial stem cells with highly pleiotropic multilineage potency in the human thymus

Thymus is necessary for lifelong immunological tolerance and immunity. It displays a distinctive epithelial complexity and undergoes age-dependent atrophy. Nonetheless, it also retains regenerative capacity, which, if harnessed appropriately, might permit rejuvenation of adaptive immunity. By characterizing cortical and medullary compartments in the human thymus at single-cell resolution, in this study we have defined specific epithelial populations, including those that share properties with bona fide stem cells (SCs) of lifelong regenerating epidermis. Thymic epithelial SCs display a distinctive transcriptional profile and phenotypic traits, including pleiotropic multilineage potency, to give rise to several cell types that were not previously considered to have shared origin. Using here identified SC markers, we have defined their cortical and medullary niches and shown that, in vitro, the cells display long-term clonal expansion and self-organizing capacity. These data substantively broaden our knowledge of SC biology and set a stage for tackling thymic atrophy and related disorders

Metamaterial architecture from a self-shaping carnivorous plant

As meticulously observed and recorded by Darwin, the leaves of the carnivorous plant Drosera capensis L. slowly fold around insects trapped on their sticky surface in order to ensure their digestion. While the biochemical signaling driving leaf closure has been associated with plant growth hormones, how mechanical forces actuate the process is still unknown. Here, we combine experimental tests of leaf mechanics with quantitative measurements of the leaf microstructure and biochemistry to demonstrate that the closure mechanism is programmed into the cellular architecture of D. capensis leaves, which converts a homogeneous biochemical signal into an asymmetric response. Inspired by the leaf closure mechanism, we devise and test a mechanical metamaterial, which curls under homogeneous mechanical stimuli. This kind of metamaterial could find possible applications as a component in soft robotics and provides an example of bio-inspired design