527 research outputs found
Integrated approach to the study of mantle cell lymphoma
No full textIl linfoma a cellule del mantello (MCL) è un linfoma non Hodgkin B caratterizzato dalla proliferazione di linfociti “maturi” che esprimono CD5, con uno spettro morfologico e fenotipico più ampio di quanto inizialmente descritto quando fu riconosciuto come entità. Sebbene alcuni pazienti abbiano un decorso clinico indolente, in molti il comportamento è aggressivo con scarsa risposta ai convenzionali regimi chemioterapici. La caratteristica genetica tipica è la traslocazione t(11;14)(q13;q32) che comporta l’iper-espressione della Ciclina D1, considerato l’evento oncogenico iniziale. Il MCL può inoltre avere alterazioni cromosomiche e molecolari secondarie che alterano ad esempio il funzionamento del controllo del ciclo cellulare, della senescenza cellulare, della risposta al danno del DNA e molte altre. La conoscenza di questi meccanismi e del loro ruolo nella crescita tumorale è fondamentale per individuare modelli prognostici dell’evoluzione clinica della malattia, nonché per lo sviluppo di nuove terapie che abbiamo come bersaglio mirato proprio le vie alterate nei MCL.
Il nostro progetto si è svolto in due fasi, una di raccolta dati da analisi del profilo proteico e fosfoproteico delle linee cellulari di MCL e una seconda di validazione su tessuto umano fissato in formalina e di sviluppo di modelli murini.Mantle cell lymphoma (MCL) is a well-defined lymphoid neoplasm characterized by a proliferation of mature B lymphocytes expressing CD5 that may show a spectrum of morphological and phenotypic features broader than initially described. Although some patients may follow an indolent clinical evolution, in most of them the tumour has an aggressive behaviour with poor response to conventional chemotherapy. The genetic hallmark is the t(11;14)(q13;q32) translocation leading to the overexpression of cyclin D1, which is considered the initial oncogenic event. In addition to this translocation, MCL may carry a high number of secondary chromosomal and molecular alterations that target regulatory elements of the cell cycle machinery and senescence (BMI1/INK4/ARF/CDK4/RB1), DNA damage response pathways (ATM/CHK2/p53), and cell survival signals. The knowledge of these mechanisms and their influence on the behaviour of the tumour are facilitating the development of prognostic models with a more precise prediction of the clinical evolution of the patients. This information coupled with the availability of a new generation of innovative drugs targeting basic molecular process of the tumour cells, should facilitate the design of new therapeutic protocols able to overcome the resistance of this aggressive lymphoma to conventional treatments and improve the life expectancy of the patients.
The goal of our project has been to integrate information from high-throughput techniques (proteomic approach), find good candidate “drivers” of MCL pathogenesis and validate them by independent techniques, especially by testing their functional importance in model systems, hopefully findings novel biomarkers that could be used in diagnostic practice.
PhosphoScan analysis identified 421 unique peptides, corresponding to 341 proteins.
Among these, several activated protein kinases were found. Interestingly, several identified proteins mapped to cytogenetic loci that have been reported to be altered in MCL by previous literature. Our data support a pro-survival role of BCR signaling in MCL and suggest that this pathway might be a candidate for therapy. Our findings also suggest that Syk activation patterns might be different in MCL compared to other lymphoma subtypes.
For validation on tissues we characterised 40 MCL cases according to most recent criteria in order to recognize biological and prognostic variants; several proteins recognized by proteomics studies were also studied in tissues by means of immunohistochemistry.
The final part of the project was focused on the attempt to establish experimental models by tumor xenografts. NOD/SCID mice were first injected by several ways with primary MCL cell in an effort to establish a model for further experimental work, but they developed GVHD and died. Then we’ve found that injecting MCL cell lines into Rag -/- γ -/- mice we were able to grow big tumoral masses
Social partenrship as public private cooperation. Thoughts from the Italian experience
No full textBottom-up initiatives in urban transformation and public goods management, as promoted by recent legislation in Italy, have been indicated by Dr. Eduardo Parisi of the University of Milan as distinctive examples of public-private cooperation that promotes efficiency and inclusion in governance.
The Author discussed how – even under the influence of the international debate – public private partnership is more and more often a cultural and social phenomenon, consistent with the principles of solidarity, participation and inclusion in governance. 
New relatedness between public and intimate sphere in Italy: an ethnographic analysis of the public and institutional debate on same-sex unions
No full textThe multiplication of the choices of procreation and filiation, thanks to the Assisted Reproductive Technologies (ARTs), has produced the disjunction of sexuality from procreation and birth, the displacement from the sexual dimension of conception to the “ideational/intentional dimension” of the pro-creative purpose. These transformations have produced an expansion of the legal-political dimension in the privacy of people's lives (Strathern, 2005; Rodotà, 2006; Plummer, 2003; Hicks, 2011). In this context, the kinship – such as « relatedness » (Carsten, 2000; 2004) – has gained a new place/platform in public debate as well as in scientific analysis, by highlighting how the interrelationship between public and private domain, and institutional and daily life dimension acts on family choices and filiation construction. This is particular evident for the families considered marginal and not fully recognised as homoparental families. Although in Italy, homoparenthood is not yet legally recognised, over the past decade the desire and choices of parenthood by the younger generation of gays and lesbians have grown (Bonaccorso, 2009; Grilli, 2014, 2016, 2018; Parisi, 2014). Homoparenting families (families where at least one parent defines him/herself as non-heterosexual) have gradually gained visibility in the collective imaginary primarily thanks to the LGBTQI activism. Same-sex family, gay and lesbian parenting have become a kind of arena of symbolic, ideological and political dispute to which different projects of society and of social ties make reference. From the proposal of a law on same-sex unions and domestic partnerships which also included the possibility to adopt the partner’s child, the debate has progressively focused in particular on gay and lesbian parenting. In this article we will consider two different moments of the legislative and social political interventions about family and procreation and the debates related to these events (in the parliament and in the public sphere). Considering the contexts and subjects involved in these debates, we will attempt to show how some themes are recurred in different situations, although with different tones and specifications. Starting from the debates generated by these legislative and institutional acts we will try to reflect on how the juridical system, the heterosexist regime, and in general the homophobic regimes are located in the heart of the construction and representation of family and kinship on the public and personal scene. In addition, we will also try to reflect on the way in which a differentialist reproductive right is produced, based on a distinction between people who can reproduce and people who cannot. An analysis of the different institutional actions and the debates generated by them, allows the making of hierarchical subjectivities from the point of view of reproductive rights
Recommended from our members
Are Individual Care Investments Affected by Past Accident Experiences?
No full textIn this paper, we analyze the impact of past accident experiences on
individual care choices. By relying on standard economic theory and evidence of
behavioral economics and psychology, we posit that individuals’ care investments
should be affected by their past accidents as injurers or victims (accident-history
effect hypothesis), or by their prior exposure to accident risks in the opposite role
(role-reversal effect hypothesis). We test these two hypotheses using experimental
data. We find that individuals’ accident history has no statistically significant
effect on their care investments, but that care decisions vary with changes in the
parties’ roles. Specifically, injurers with prior experience as victims invest statistically
more in care than injurers without prior victim experience. By contrast, care
investments are not sensitive to victims’ prior experience as injurers. Our research
can be regarded as a preliminary study toward the understanding of the role of past
accident experiences on individuals’ care behavior, and calls for both replication
efforts and reconsideration of traditional economic models of torts
Injurers versus Victims: (A)Symmetric Reactions to Symmetric Risks
No full textTort models assume symmetry in the behavior of injurers and victims when faced by a threat of liability and a risk of harm without compensation, respectively. This assumption has never been empirically validated. Using a novel experimental design, we study the behavior of injurers and victims when facing symmetric accident risks. Experimental results provide qualified support for the symmetric behavior hypothesis
Investing in Private Evidence: The Effect of Adversarial Discovery
No full textMuch of the conventional wisdom of evidence law rests on the premise that the
amount of evidence available in any given case is exogenously determined. With the
advent of evidence technology (e.g. dashcams, black-box technology, digital data storage, surveillance cameras), the availability of evidence is substantially controlled by
individuals. In this article, we show that evidence rules play an important role in determining individuals’ decisions to invest in private evidence. We compare the evidence
rules adopted in the USA and Europe and analyze their relative impact on the voluntary
adoption of evidence technology. We find that by making private evidence not discoverable, more rather than less evidence would be made available to courts
Recommended from our members
Second, But Not Last: Competition with Positive Spillovers
No full textThis paper extends the traditional rent-seeking model to consider contests in which the effects of the contestants’ efforts are externally unproductive (i.e., redistributive) but internally productive (i.e., with positive spillover effects on other contestants). Our results show that when players act sequentially, the presence of positive spillovers on other contestants may reduce, or even reverse, the first-mover’s advantage. A second-mover advantage is very likely to arise. Notably, in contests with multiple players, the second-mover advantage does not unravel into a last-mover advantage. Players want to be second, but not last. The comparative statics analysis shows how the strength of positive spillovers affects contestants’ equilibrium expenditures and payoffs, and aggregate rent dissipation
Interactions between Reflection and Praxis in the History of Economic Thought. The case of the Franciscan Cicles from XIII Century Assisi to the Present
No full textResumen: Daniela Parisi analiza el impacto de la vida de San F rancisco de Asís desde la perspectiva de la historia del pensamiento económico. Haciendo referencia particularmente a la atención otorgada en los círculos franciscanos a los signos de los tiempos, la autora traza el camino desde la vida de San Francisco, pasando por la vida de la Orden hasta el presente, y revela los orígenes del movimiento franciscano como un intento de reforma social y religiosa. En primer lugar, el artículo presenta la vida que llevó San Francisco como una “pobreza material voluntaria” en el contexto de los cambios socio-económicos que tuvieron lugar en el siglo XIII, con el advenimiento de la sociedad comercial. Luego, explica cómo la propuesta de San Francisco creció hasta convertirse en una orden religiosa. Finalmente, el artículo intenta iluminar aquellos aspectos en que la Orden Franciscana puede todavía considerarse un signo de los tiempos a través de una existencia comprometida con la pobreza, eliminando lo superfluo de nuestra vida y viviendo en consonancia con el Evangelio.Abstract: Daniela Parisi analyses the impact of the life of Saint Francis of Assisi, from the perspective of the history of economic thought. By referring in particular to the attention given in Franciscan circles to the signs of times, the author draws the path from Saint Francis’s life to the life of the Order until the present, and reveals the origins of the Franciscan movement as an attempt for social and religious reformation. First, the article presents St. Francis’s life of a “voluntary material poverty” in the context of the social and economic changes that took place in the XIII century, with the rise of the commercial society. Then, the author explains how St. Francis’ proposal grew into an Order. Finally, the article aims at illuminating the aspects in which the Franciscan Order can be still considered a sign of the times by living the commitment to poverty and minority, eliminating the superfluous from our lives and living close to the Gospel
Malthodes (Malthodes) marialuisae Parisi & Fanti 2020
No full textMalthodes (Malthodes) marialuisae PARISI & FANTI sp. nov. (Figs. 7–8, 11C) Description. Male, winged. Body length 4.2 mm; elytra 1.1 mm; pronotum 0.2 mm; antennae about 4.4 mm. Entirely blackish-dark brown, without yellow spots on the elytral apex. Head exposed, rounded, with shallow punctation. Eyes rounded, very prominent, inserted in the lateral-upper part of the head. Maxillary palpi 4-segmented, with the last palpomere globular and distally pointed (point thin and very elongate). Labial palpi 3-segmented, last palpomere globular and distally pointed. Antennae filiform, 11-segmented, extremely long, slightly surpassing the last abdominal segment; antennomere I very elongate, club-shaped; antennomere II enlarged apically and about 1.3 times shorter than antennomere I; antennomere III enlarged apically and slightly shorter than antennomere II; antennomeres IV–VIII sub-equal and very elongate; antennomere IX very slightly shorter than previous ones; antennomere X shorter than previous; antennomere XI elongate and with rounded apex; all antennomeres densely covered by short setae. Pronotum transverse, narrower than the head, surface with sparce punctation, anterior margin undulate, posterior margin straight and slightly bordered, sides straight and slightly bordered. Elytra very short, reaching the middle of the abdomen, slightly wider than pronotum, covered with scattered and short setae, parallel-sided, rounded at apices. Hind wings transparent, almost reaching the last abdominal segment (left wing totally extroverted and equipped with few nervations well visible). Legs long, slender, densely pubescent; coxae elongate; trochanters robust with rounded apex; femora slightly enlarged and almost straight; tibiae cylindrical with a spur near the apex, pro- and metatibiae shorter than pro- and metafemora, mesotibiae longer than mesofemora; tarsi 5-segmented, pubescent; tarsomeres I thin, elongate; tarsomeres II slightly enlarged apically and shorter than tarsomeres I; tarsomeres III short, triangular-shaped; tarsomeres IV strongly bilobed and robust; tarsomeres V elongate and slender; claws simple. Metasternum sub-quadrate. Sternites transverse and pubescent. Last tergite (tg10) in the shape of an elongate and broad lobe, strongly curved, narrower to the middle, with the apical margin sinuous equipped with two small points at the middle and with the apical sides slightly expanded; last sternite (st9) short, elongate, curved, flat and apically deeply forked (with robust, apically rounded lobes). Aedeagus not visible. Female unknown. Etymology. Named in honor of Marialuisa Vessella, mother of the first author. Holotype. Male, in Baltic amber, deposited at the University of Molise (Unimol) with accession No. Unimol AAA006FP. Type locality. Yantarny mine, Sambian Peninsula, Kaliningrad region, Russia. Type horizon. Middle Eocene (Lutetian) (47.8–41.2 MYA) to Late Eocene (Priabonian) (37.8–33.9 MYA). Syninclusions. Air bubbles, debris, stellate hairs, a disarticulated spider. Differential diagnosis. The shape of the penultimate and last tergite makes Malthodes marialuisae sp. nov. unique and easily distinguishable from all the known fossil species of Malthodes, both from Baltic amber, Bitterfeld amber, and Rovno amber (Fanti 2017, 2019; Fanti & Vitali 2017; Fanti & Sontag 2019; Parisi & Fanti 2019c). Remarks. The yellow amber piece measures 15 x 8 x 3 mm. The inclusion is complete except for the left antenna preserved up to the sixth antennomere and has also extruded left elytron with the metathoracic wing clearly visible.Published as part of Parisi, Francesco & Fanti, Fabrizio, 2020, Baltic amber: A new Cacomorphocerus Schaufuss, 1892 with two specimens preserved in a single piece, and four new Malthodes Kiesenwetter, 1852, pp. 546-560 in Zootaxa 4778 (3) on pages 553-555, DOI: 10.11646/zootaxa.4778.3.6, http://zenodo.org/record/382878
Misoprostol administration prior to intrauterine contraceptive device insertion: a systematic review and meta-analysis of randomised controlled trials
No full textObjectives: Misoprostol has been used before intrauterine contraceptive device (IUCD) insertion to prime the cervical os. As the literature about this topic is controversial, we aimed to evaluate IUCD insertion failure, women's pain perception, use of cervical dilators and prevalence of side effects following the administration of misoprostol. Methods: Trials published in MEDLINE, Scopus, the Cochrane Library and ClinicalTrials.gov were searched (last search on 23 October 2019). The primary outcome was IUCD insertion failure; secondary outcomes were women's pain perception, use of cervical dilators to facilitate insertion, and prevalence of side effects. Results: Fourteen studies were eligible for inclusion. Misoprostol premedication reduced IUCD insertion failure rates and the use of cervical dilators but significantly increased the prevalence of side effects. The risk of IUCD insertion failure with misoprostol premedication was reduced among women who had undergone previous caesarean section and among women who had experienced previous IUCD insertion failure. Nulliparas did not benefit from misoprostol premedication. Buccal misoprostol administration did not seem to be effective in reducing IUCD insertion failure. Visual analogue scale pain scores were increased with both sublingual and buccal misoprostol administration if IUCD insertion was performed <= 2.5 h after misoprostol premedication. Conclusion: Our data demonstrate reduced IUCD insertion failure among women with previous caesarean section and those with previous IUCD insertion failure, suggesting that misoprostol may be a reasonable choice in these groups of women. Although misoprostol premedication reduced insertion failures, it significantly increased side effects and had a heterogeneous pattern of efficacy; thus, its routine use is not supported by the evidence
- …
