THE COMMUNICATION OF TERRITORIAL IDENTITY VALUE THROUGH LARGE SCALE HISTORICAL MAPS

I valori identitari del territorio sono strettamente legati alla dimensione diacronica e si esprimono attraverso i processi di territorializzazione. Le carte storiche peritali, che offrono una rappresentazione di dettaglio del territorio, contribuiscono non solo a conoscerne e ad evidenziarne il patrimonio storico-culturale; ma possiedono inoltre, grazie ad una valenza di tipo estetico, anche un’intrinseca capacità comunicativa oltre ad un indubitabile valore scientifico. Il rapporto percettivo che l’osservatore instaura con esse è infatti enorme e immediato: è un valore aggiunto prezioso per la didattica di qualsiasi livello formativo. Se confrontate con la cartografia moderna le carte storiche possono ben dar conto sia delle trasformazioni profonde del territorio e del paesaggio, avvenute nel corso dei secoli, sia delle persistenze che si esprimono nella presenza di beni materiali ma anche nella toponomastica o in una certa compartimentazione del territorio, evidenziando i condizionamenti storici della realtà presente.The individuality of a territory is strictly connected with the diacronic dimension and comes to existence through territorialisation processes. Large scale historical maps play a very important role in drawing attention to the historical–cultural heritage of a place and, in addition to their undouted scientific value, they exert a significant communication power, thanks also to their beauty. The perceptive relationship that the observer establishes with them is enormous and immediate; thus it represents a precious tool for teaching at any educational level. Finally, when used in concert with modern carthograpy, historical maps are able to point out the deep territorial and landscape transformations, which occurred during the centuries, underlining both tangible and intangible elements of the historical heritage. Hence, by highlighting the signs of the past in the present contexts, they enable a more conscious approach to territorial planning

Additional modifications to the Blumgart pancreaticojejunostomy: Results of a propensity score-matched analysis versus Cattel-Warren pancreaticojejunostomy

Abstract Background Postoperative pancreatic fistula continues to occur frequently after pancreatoduodenectomy. Methods We have described a modification of the Blumgart pancreaticojejunostomy. The modification of the Blumgart pancreaticojejunostomy was compared to the Cattel-Warren pancreaticojejunostomy in cohorts of patients matched by propensity scores based on factors predictive of clinically relevant postoperative pancreatic fistula, which was the primary endpoint of this study. Based on a noninferiority study design, 95 open pancreatoduodenectomies per group were needed. Feasibility of the modification of the Blumgart pancreaticojejunostomy in robotic pancreatoduodenectomy was also shown. All pancreaticojejunostomies were performed by a single surgeon. Results Between October 2011 and May 2019, there were 415 pancreatoduodenectomies with either a Cattel-Warren pancreaticojejunostomy (n = 225) or a modification of the Blumgart pancreaticojejunostomy (n = 190). There was 1 grade C postoperative pancreatic fistula in 190 consecutive modification of the Blumgart pancreaticojejunostomies (0.5%). Logistic regression analysis showed that the rate of clinically relevant postoperative pancreatic fistula was not affected by consecutive case number. After exclusion of robotic pancreatoduodenectomies (the Cattel-Warren pancreaticojejunostomy: 82; modification of the Blumgart pancreaticojejunostomy: 66), 267 open pancreatoduodenectomies were left, among which the matching process identified 109 pairs. The modification of the Blumgart pancreaticojejunostomy was shown to be noninferior to the Cattel-Warren pancreaticojejunostomy with respect to clinically relevant postoperative pancreatic fistula (11.9% vs 22.9%; odds ratio: 0.46 [0.21–0.93]; P = .03), grade B postoperative pancreatic fistula (11.9% vs 18.3%; P = .18), and grade C postoperative pancreatic fistula (0 vs 4.6%; P = .05) as well as to all secondary study endpoints. The modification of the Blumgart pancreaticojejunostomy was feasible in 66 robotic pancreatoduodenectomies. In this subgroup with 1 conversion to open surgery (1.5%), a clinically relevant postoperative pancreatic fistula occurred after 9 procedures (13.6%) with no case of grade C postoperative pancreatic fistula and a 90-day mortality of 3%. Conclusion The modification of the Blumgart pancreaticojejunostomy described herein is noninferior to the Cattel-Warren pancreaticojejunostomy in open pancreatoduodenectomy. This technique is also feasible in robotic pancreatoduodenectomy

Polymorphic variants of IGF2BP3 and SENCR have an impact on predisposition and/or progression of Ewing sarcoma

Ewing sarcoma (EWS), the second most common malignant bone tumor in children and adolescents, occurs abruptly without clear evidence of tumor history or progression. Previous association studies have identified some inherited variants associated with the risk of developing EWS but a common picture of the germline susceptibility to this tumor remains largely unclear. Here, we examine the association between thirty single nucleotide polymorphisms (SNPs) of the IGF2BP3, a gene that codes for an oncofetal RNA-binding protein demonstrated to be important for EWS patient's risk stratification, and five SNPs of SENCR, a long non-coding RNA shown to regulate IGF2BP3. An association between polymorphisms and EWS susceptibility was observed for three IGF2BP3 SNPs - rs112316332, rs13242065, rs12700421 - and for four SENCR SNPs - rs10893909, rs11221437, rs12420823, rs4526784 -. In addition, IGF2BP3 rs34033684 and SENCR rs10893909 variants increased the risk for female respect to male subgroup when carried together, while IGF2BP3 rs13242065 or rs76983703 variants reduced the probability of a disease later onset (> 14 years). Moreover, the absence of IGF2BP3 rs10488282 variant and the presence of rs199653 or rs35875486 variant were significantly associated with a worse survival in EWS patients with localized disease at diagnosis. Overall, our data provide the first evidence linking genetic variants of IGF2BP3 and its modulator SENCR to the risk of EWS development and to disease progression, thus supporting the concept that heritable factors can influence susceptibility to EWS and may help to predict patient prognosis

The clonal evolution of two distinct T315I-positive BCR-ABL1 subclones in a Philadelphia-positive acute lymphoblastic leukemia failing multiple lines of therapy: a case report

BACKGROUND: The treatment of Philadelphia chromosome-positive Acute Lymphoblastic Leukemia (Ph+ ALL) patients who harbor the T315I BCR-ABL1 mutation or who have two or more mutations in the same BCR-ABL1 molecule is particularly challenging since first and second-generation Tyrosine Kinase Inhibitors (TKIs) are ineffective. Ponatinib, blinatumomab, chemotherapy and transplant are the currently available options in these cases. CASE PRESENTATION: We here report the case of a young Ph+ ALL patient who relapsed on front-line dasatinib therapy because of two independent T315I-positive subclones, resulting from different nucleotide substitutions -one of whom never reported previously- and where additional mutant clones outgrew and persisted despite ponatinib, transplant, blinatumomab and conventional chemotherapy. Deep Sequencing (DS) was used to dissect the complexity of BCR-ABL1 kinase domain (KD) mutation status and follow the kinetics of different mutant clones across the sequential therapeutic approaches. CONCLUSIONS: This case presents several peculiar and remarkable aspects: i) distinct clones may acquire the same amino acid substitution via different nucleotide changes; ii) the T315I mutation may arise also from an 'act' to 'atc' codon change; iii) the strategy of temporarily replacing TKI therapy with chemo or immunotherapy, in order to remove the selective pressure and deselect aggressive mutant clones, cannot always be expected to be effective; iv) BCR-ABL1-mutated sub-clones may persist at very low levels (undetectable even by Deep Sequencing) for long time and then outcompete BCR-ABL1-unmutated ones becoming dominant even in the absence of any TKI selective pressure

Chapter Digi Skills Bsc – Revising Graphic Literacy in Bsc Architectural Design Education through a Software-Based Pedagogic Approach. A Shared Pilot Experience at the Politecnico di Milano

The 43rd UID conference, held in Genova, takes up the theme of ‘Dialogues’ as practice and debate on many fundamental topics in our social life, especially in these complex and not yet resolved times. The city of Genova offers the opportunity to ponder on the value of comparison and on the possibilities for the community, naturally focused on the aspects that concern us, as professors, researchers, disseminators of knowledge, or on all the possibile meanings of the discipline of representation and its dialogue with ‘others’, which we have broadly catalogued in three macro areas: History, Semiotics, Science / Technology. Therefore, “dialogue” as a profitable exchange based on a common language, without which it is impossible to comprehend and understand one another; and the graphic sign that connotes the conference is the precise transcription of this concept: the title ‘translated’ into signs, derived from the visual alphabet designed for the visual identity of the UID since 2017. There are many topics which refer to three macro sessions: - Witnessing (signs and history) - Communicating (signs and semiotics) - Experimenting (signs and sciences) Thanks to the different points of view, an exceptional resource of our disciplinary area, we want to try to outline the prevailing theoretical-operational synergies, the collaborative lines of an instrumental nature, the recent updates of the repertoires of images that attest and nourish the relations among representation, history, semiotics, sciences

5′UTR point substitutions and N-terminal truncating mutations of ANKRD26 in acute myeloid leukemia

Thrombocytopenia 2 (THC2) is an inherited disorder caused by monoallelic single nucleotide substitutions in the 5'UTR of the ANKRD26 gene. Patients have thrombocytopenia and increased risk of myeloid malignancies, in particular, acute myeloid leukemia (AML). Given the association of variants in the ANKRD26 5'UTR with myeloid neoplasms, we investigated whether, and to what extent, mutations in this region contribute to apparently sporadic AML. To this end, we studied 250 consecutive, non-familial, adult AML patients and screened the first exon of ANKRD26 including the 5'UTR. We found variants in four patients. One patient had the c.-125T>G substitution in the 5'UTR, while three patients carried two different variants in the 5' end of the ANKRD26 coding region (c.3G>A or c.105C>G). Review of medical history showed that the patient carrying the c.-125T>G was actually affected by typical but unrecognized THC2, highlighting that some apparently sporadic AML cases represent the evolution of a well-characterized familial predisposition disorder. As regards the c.3G>A and the c.105C>G, we found that both variants result in the synthesis of N-terminal truncated ANKRD26 isoforms, which are stable and functional in cells, in particular, have a strong ability to activate the MAPK/ERK signaling pathway. Moreover, investigation of one patient with the c.3G>A showed that mutation was associated with strong ANKRD26 overexpression in vivo, which is the proposed mechanism for predisposition to AML in THC2 patients. These data provide evidence that N-terminal ANKRD26 truncating mutations play a potential pathogenetic role in AML. Recognition of AML patients with germline ANKRD26 pathogenetic variants is mandatory for selection of donors for bone marrow transplantation

In chronic myeloid leukemia patients on second-line tyrosine kinase inhibitor therapy, deep sequencing of BCR-ABL1 at the time of warning may allow sensitive detection of emerging drug-resistant mutants

BACKGROUND: Imatinib-resistant chronic myeloid leukemia (CML) patients receiving second-line tyrosine kinase inhibitor (TKI) therapy with dasatinib or nilotinib have a higher risk of disease relapse and progression and not infrequently BCR-ABL1 kinase domain (KD) mutations are implicated in therapeutic failure. In this setting, earlier detection of emerging BCR-ABL1 KD mutations would offer greater chances of efficacy for subsequent salvage therapy and limit the biological consequences of full BCR-ABL1 kinase reactivation. Taking advantage of an already set up and validated next-generation deep amplicon sequencing (DS) assay, we aimed to assess whether DS may allow a larger window of detection of emerging BCR-ABL1 KD mutants predicting for an impending relapse. METHODS: a total of 125 longitudinal samples from 51 CML patients who had acquired dasatinib- or nilotinib-resistant mutations during second-line therapy were analyzed by DS from the time of failure and mutation detection by conventional sequencing backwards. BCR-ABL1/ABL1%(IS) transcript levels were used to define whether the patient had 'optimal response', 'warning' or 'failure' at the time of first mutation detection by DS. RESULTS: DS was able to backtrack dasatinib- or nilotinib-resistant mutations to the previous sample(s) in 23/51 (45 %) pts. Median mutation burden at the time of first detection by DS was 5.5 % (range, 1.5-17.5 %); median interval between detection by DS and detection by conventional sequencing was 3 months (range, 1-9 months). In 5 cases, the mutations were detectable at baseline. In the remaining cases, response level at the time mutations were first detected by DS could be defined as 'Warning' (according to the 2013 ELN definitions of response to 2nd-line therapy) in 13 cases, as 'Optimal response' in one case, as 'Failure' in 4 cases. No dasatinib- or nilotinib-resistant mutations were detected by DS in 15 randomly selected patients with 'warning' at various timepoints, that later turned into optimal responders with no treatment changes. CONCLUSIONS: DS enables a larger window of detection of emerging BCR-ABL1 KD mutations predicting for an impending relapse. A 'Warning' response may represent a rational trigger, besides 'Failure', for DS-based mutation screening in CML patients undergoing second-line TKI therapy

Microbial colonization patterns and biodegradation of petrochemical and biodegradable plastics in lake waters: insights from a field experiment

IntroductionOnce dispersed in water, plastic materials become promptly colonized by biofilm-forming microorganisms, commonly known as plastisphere.MethodsBy combining DNA sequencing and Confocal Laser Scanning Microscopy (CLSM), we investigated the plastisphere colonization patterns following exposure to natural lake waters (up to 77 days) of either petrochemical or biodegradable plastic materials (low density polyethylene - LDPE, polyethylene terephthalate - PET, polylactic acid - PLA, and the starch-based MaterBi® - Mb) in comparison to planktonic community composition. Chemical composition, water wettability, and morphology of plastic surfaces were evaluated, through Transform Infrared Spectroscopy (ATR-FTIR), Scanning Electron Microscopy (SEM), and static contact angle analysis, to assess the possible effects of microbial colonization and biodegradation activity.Results and DiscussionThe phylogenetic composition of plastisphere and planktonic communities was notably different. Pioneering microbial colonisers, likely selected from lake waters, were found associated with all plastic materials, along with a core of more than 30 abundant bacterial families associated with all polymers. The different plastic materials, either derived from petrochemical hydrocarbons (i.e., LDPE and PET) or biodegradable (PLA and Mb), were used by opportunistic aquatic microorganisms as adhesion surfaces rather than carbon sources. The Mb-associated microorganisms (i.e. mostly members of the family Burkholderiaceae) were likely able to degrade the starch residues on the polymer surfaces, although the Mb matrix maintained its original chemical structure and morphology. Overall, our findings provide insights into the complex interactions between aquatic microorganisms and plastic materials found in lake waters, highlighting the importance of understanding the plastisphere dynamics to better manage the fate of plastic debris in the environment

Cyclic Vomiting Syndrome in Children

Cyclic Vomiting Syndrome (CVS) is an underdiagnosed episodic syndrome characterized by frequent hospitalizations, multiple comorbidities, and poor quality of life. It is often misdiagnosed due to the unappreciated pattern of recurrence and lack of confirmatory testing. CVS mainly occurs in pre-school or early school-age, but infants and elderly onset have been also described. The etiopathogenesis is largely unknown, but it is likely to be multifactorial. Recent evidence suggests that aberrant brain-gut pathways, mitochondrial enzymopathies, gastrointestinal motility disorders, calcium channel abnormalities, and hyperactivity of the hypothalamic-pituitary-adrenal axis in response to a triggering environmental stimulus are involved. CVS is characterized by acute, stereotyped and recurrent episodes of intense nausea and incoercible vomiting with predictable periodicity and return to baseline health between episodes. A distinction with other differential diagnoses is a challenge for clinicians. Although extensive and invasive investigations should be avoided, baseline testing toward identifying organic causes is recommended in all children with CVS. The management of CVS requires an individually tailored therapy Management of acute phase is mainly based on supportive and symptomatic care. Early intervention with abortive agents during the brief prodromal phase can be used to attempt to terminate the attack. During the interictal period, non-pharmacologic measures as lifestyle changes and the use of reassurance and anticipatory guidance seem to be effective as a preventive treatment. The indication for prophylactic pharmacotherapy depends on attack intensity and severity, the impairment of the QoL and if attack treatments are ineffective or cause side effects. When children remain refractory to acute or prophylactic treatment, or the episode differs from previous ones, the clinician should consider the possibility of an underlying disease and further mono- or combination therapy and psychotherapy can be guided by accompanying comorbidities and specific sub-phenotype. This review was developed by a joint task force of the Italian Society of Pediatric Gastroenterology Hepatology and Nutrition (SIGENP) and Italian Society of Pediatric Neurology (SINP) to identify relevant current issues and to propose future research directions on pediatric CV