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Descriptive statistics of the primary and secondary endpoint measurements.

Boxplot reflecting the distribution of 15-PGDH expression at baseline (T0) and at six months (T2) according to the Aperio ScanScope Cytoplasm Algorithm V2. Each box indicates the 25th and 75th percentiles of the distribution. The horizontal line inside the box indicates the median and the whiskers indicate the extreme measured values; the mean value is represented by a black diamond.

Panel A-1: COX-2 IHC performed on normal FAP biopsies collected before the dietary intervention (T0) and after six months of diet (T2). Panel A-2: COX-2 IHC performed on adenoma FAP biopsies at T0 and T2. Panel B-1: COX-2 IHC performed on normal colon mucosa collected from surgery for sporadic colon cancer. Panel B-2: 15-PGDH IHC performed on normal colon mucosa collected from surgery for sporadic colon cancer.

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L’articolo propone una breve storia della nozione di “otium” dall’antichità ai nostri giorni. Mostra come nella Greciaantica la vita oziosa viene considerata onorevole e come invece vengono condannati il “lavoro”, inteso nel senso di assenza dilibertà, e la ricerca della ricchezza come fine a se stessa. Queste idee riappaiono nel corso della storia, ad esempio, nella trattatistica del comportamento che fiorisce nel Rinascimento, negli ideali cortigiani, cosi’ come tra le classi marginali della società.

O artigo propõe uma breve história da noção de “otium” desde a Antiguidade até os nossos dias. Mostra como, na Grécia antiga, a vida ociosa é considerada honorável e o trabalho é condenado, entendido no sentido de ausência de liberdade e de busca de riqueza como um fim em si mesma. Essas ideias reaparecem no curso da história, por exemplo, na tratadística do comportamento que floresce no Renascimento, nos ideais cortesãos, assim como entre as classes marginais da sociedade.

We carefully read the comment by Serrano et al. [...].

Introduction: About 5% of endometrial cancers (ECs) are attributed to an inherited predisposition, for which Lynch syndrome (LS) accounts for the majority of cases. Women with LS have a 40–60% predicted lifetime risk of developing EC, in addition to a 40–80% lifetime risk of developing colorectal cancer and other cancers. In this population, the lifetime risk of developing ovarian cancer (OC) is 10–12%. Object: to compare the histopathological features of LS-associated EC and OC with sporadic cancers in order to evaluate whether there are differences in terms of age at diagnosis, site of occurrence in the uterus, histological type, stage at diagnosis, and tumor grading. Materials and methods: we compared data obtained from 96 patients with LS-associated gynecological cancers (82 with EC and 14 with OC) to a control group (CG) of 209 patients who developed sporadic EC, and a CG of 187 patients with sporadic OC. Results: The mean age at diagnosis of LS-associated EC and OC was much lower than in the control groups. In both groups with EC, the endometrioid histotype was the most frequently occurring histotype. However, among LS women there was a significantly higher incidence of clear cell tumors (11% versus 2.4% in the CG, p = 0.0001). Similar to the sporadic cancer cases, most of the LS-associated ECs presented at an early stage (89% of cases at FIGO I-II stage). In the LS group, the tumor frequently involved only the inner half of the endometrium (77% of cases, p < 0.01). In the LS group, 7.3% of ECs were localized to the lower uterine segment (LUS), whereas no cancer developed in the LUS in the CG. No serous OCs were diagnosed in the LS group (versus 45.5% in the CG, p = 0.0009). Most of the LS-associated OCs presented at an early stage (85% of cases at FIGO I-II stages, p < 0.01). Conclusion: LS-associated EC and OC seem to have peculiar features, occurring at a younger age and at an earlier stage. In LS, EC less frequently involves the outer half of the endometrium, with a more frequent occurrence in the LUS. The presence of clear cell EC was more frequently observed, whereas in OC, the predominant histotype was endometrioid.

Risk factors for metachronous colorectal cancer (mCRC) in Lynch Syndrome (LS) patients are essential for colorectal cancer (CRC) treatment strategy to perform not only a curative but also preventive surgery. The aim of this study was to evaluate the risk factors for mCRC development in LS patients to define the patient subset that may benefit an extended curative and preventive surgical resection. Patient’s clinical history, oncological, molecular and follow-up were collected retrospectively from the Hereditary Digestive Tumors Registry at the National Cancer Institute of Milan. The age-related cumulative risk of mCRC was calculated using the Kaplan–Meier method. Factors significantly associated with mCRC were analyzed with a Cox regression model. Overall and specific competitive risks were also calculated. In a total of 1346 CRC patients, 159 (11.8%) developed a mCRC after a mean follow-up of 138 months from the primary tumor. The independent risk factors reported by a multivariate analysis were: pathogenetic variants in MLH1 and MSH2 (HR 2.96 and 1.91, respectively) and history of colorectal adenomas (HR 1.54); whereas female sex and extended surgery were protective (HR 0.59 and 0.79, respectively). Among a high-risk population for CRC, in particular LS, an extended surgery may be considered in CRC patients with specific risk factors (MLH1 or MSH2 germline pathogenic variants, history of colorectal adenomas) to reduce the risk of mCRC development.

Mini-EUSO is a new space-based experiment designed primarily to observe showers that develop in atmosphere due to the interaction between molecular nitrogen and Ultra High Energy Cosmic particles (above 1021 eV) crossing by. It belongs to the JEM-EUSO program, which includes several past experiments all devoted to develop new larger size satellite detectors like K-EUSO and POEMMA for future UHEC Rays study from space. Mini-EUSO is a multiwavelenght telescope launched on August 2019 with the unmanned Soyuz MS-14 rocket to the International Space Station and currently operating on board the Russian Zvezda module, facing a UV-transparent window watching Earth in Nadir direction. The telescope optics comprise a main detection system employing two double-sided Fresnel lenses focusing UV (300–400 nm) light onto an array of 36 Hamamatsu Multi-Anode PhotoMultiplier Tubes, each of 64 channels for a total of 2304 pixels working in single photon counting mode, providing a wide field of view (44°) correpsonding to a ground area of 263 x 263 km2 with a highly fast time resolution up to few microseconds. Mini-EUSO includes also multiple ancillary sensors such as visible (400–780 nm) and NIR (1500–1600 nm) cameras covering a wide range of radiation wavelenght as well as a 64 channels Multi-Pixel Photon Counter Silicon PhotoMultiplier array which will increase the Technology Readiness Level of this ultrafast imaging sensor. Beside the primary objective, the mission aims to study different event such as meteoroids, Transient Luminous Event, search for Strange Quark matter and thanks to its space-time resolution is capable to provide UV Earth maps over the surface covered during ISS orbits. In this work we will present the detector integration, the qualification measurements on ground and some preliminary data.

Preimplantation genetic testing for monogenic/single-gene disorders (PGT-M) is a procedure employed in the field of assisted reproductive technology to avoid the transmission of genetic diseases to the offspring. Hereditary cancer syndromes represent a diffuse and accepted indication for PGT-M, but take-up differs among the different disorders. Its use is markedly lower for the genes causing Lynch syndrome compared with the breast cancer type 1 or 2 susceptibility genes (BRCA1/2), despite the similar prevalence and severity of the two conditions. Reasons to explain this difference have not been explored. First, Lynch syndrome may be more frequently undiagnosed compared with hereditary breast and ovarian cancer syndrome. In addition, the different take-up may be due to different patient perceptions of the conditions and of the management options. Finally, this distinct attitude may depend on the awareness and sensibility of the professionals caring for affected patients. The authors' considerations are, however, speculative, and specific studies aimed at disentangling the causes of the different receptions of PGT-M are warranted to understand how to tackle this gap. In the meantime, we believe that empowerment regarding PGT-M of all individuals with hereditary cancer syndromes, including Lynch syndrome, is ethically due, and plead for a more active involvement of caregivers.

ObjectiveWomen with Lynch syndrome have a risk up to 40–60% of developing endometrial cancer, which is higher than their risk of developing colorectal or ovarian cancer. To date, no data on the outcomes of patients with Lynch syndrome diagnosed with non-endometrioid endometrial cancer are available. The goal of this study was to evaluate the outcome of patients with Lynch syndrome diagnosed with non-endometrioid endometrial cancer.MethodsData from consecutive patients diagnosed with Lynch syndrome and with a histological diagnosis of non-endometrioid endometrial cancer were retrospectively collected in two referral institutes in Italy. A case–control comparison (applying a propensity matching algorithm) was performed in order to compare patients with proven Lynch syndrome and controls. Inclusion criteria were: (a) histologically-proven endometrial cancer; (b) detection of a germline pathogenic variant in one of the MMR genes; (c) adequate follow-up. Only carriers of pathogenic or likely pathogenic variants (ie, class 5 and 4 according to the InSiGHT classification) were included in the study. Survival outcomes were assessed using KaplanMeier and Cox models.ResultsOverall, 137 patients with Lynch syndrome were collected. Mean patient age was 49.2 (10.9) years. Genes involved in the Lynch syndrome included MLH1, MSH2, and MSH6 in 43%, 39%, and 18% of cases, respectively. The study population included 27 patients with non-endometrioid endometrial cancer, who were matched 1:2 with patients with sporadic cancers using a propensity matching algorithm. After a median follow-up of 134 months (range 1–295), 2 (7.4%) of the 27 patients developed recurrent disease (3 and 36 months) and subsequently died of disease (7 and 91 months). Patients diagnosed with Lynch syndrome experienced better disease-free survival (HR 7.86 (95% CI 1.79 to 34.5); p=0.006) and overall survival (HR 5.33 (95% CI 1.18 to 23.9); p=0.029) than controls.ConclusionsNon-endometrioid endometrial cancer occurring in patients with Lynch syndrome might be associated with improved oncologic outcomes compared with controls. Genetic/molecular profiling should be investigated in order to better understand the mechanism underlying the prognosis.

Partindo da análise da etimologia da palavra “graça”, a autora analisa a teoria de Castiglione, condensada na frase “quem tem graça, é grato”, que indica tanto um sentido ativo, quanto um sentido passivo da palavra “graça”. Para receber a graça de seu príncipe, o nobre cortesão deve ser gracioso. A “graça”, portanto, torna-se um ornamento e uma estratégia. A “graça” nasce de uma “regra universal”: evitar afetação e demonstrar certa indiferença – sprezzatura. Sprezzatura, que implica disprezzo, desdém, é dissimulação da arte e similação de natureza. É o produto de uma longa “fadiga” que deve ficar completamente escondida. A “graça” pode ser, deste modo, resumida no oxímoro: arte sem arte.

Introduction: Familial adenomatous polyposis (FAP) is a hereditary autosomal dominant disorder characterized by the development of multiple adenomas in the colon and rectum with a lifetime risk of 80%–100% to develop colorectal cancer if undetected or untreated. Gardner-associated fibroma (GAF) is a rare, benign soft tissue lesion with uncertain pathogenesis. GAF is generally associated with FAP in its clinical variant, called Gardner syndrome (GS). Case Description: A 16-year-old boy with no comorbidities and no significant medical history was referred to the Unit of Hereditary Digestive Tract Tumours, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, for genetic counselling after surgical removal of a right anterior cervical paramedian fibroma. The histopathology on the specimen led to the diagnosis of GAF. He had no family history for colorectal cancer or gastrointestinal polyposis and denied any gastrointestinal symptoms. Physical examination showed a small frontal osteoma and colonoscopy showed the presence of multiple small sessile polyps (>100 polyps, diameter Conclusions: GAF may represent a sentinel sign of FAP, preceding gastrointestinal symptoms and endoscopic findings. A careful multidisciplinary approach is determinant for correct and early diagnosis of FAP.

Although duodenal adenomas and cancer appear to occur significantly less frequently in autosomal recessive MUTYH-associated polyposis (MAP) than in autosomal dominant familial adenomatous polyposis (FAP),1 current guidelines recommend similar endoscopic surveillance for both disorders.2-4 This involves gastro-duodenoscopy starting at 25 to 35 years of age and repeated at intervals determined by Spigelman staging based on the number, size, histological type and degree of dysplasia of adenomas, and by ampullary staging. Case reports of duodenal cancers in MAP suggest that they may develop in the absence of advanced Spigelman stage benign disease and even without coexisting adenomas.1 Recent molecular analyses suggest thatMAPduodenal adenomashave a higher mutational burden than FAP adenomas and are more likely to harbor oncogenic drivermutations, such as those in KRAS.5 These apparent differences in the biology and natural history of duodenal polyposis in FAP and MAP challenge the assumption that the same surveillance should be applied in both conditions.

Introduction Mutations of the APC (adenomatous polyposis coli) gene correlate mainly with familial adenomatous polyposis (FAP), but can occasionally be pathogenic for medulloblastoma (MBL) wingless-related integration site (WNT) subtype, the course of which has only recently been described. Methods We retrieved all patients with documented germline APC mutations and a diagnosis of MBL to examine their outcome, late effects of treatment, and further oncological events. Results Between 2007 and 2016, we treated six patients, all with a pathogenic APC variant mutation and all with MBL, classic histotype. None had metastatic disease. All patients were in complete remission a median 65 months after treatment with craniospinal irradiation at 23.4 Gy, plus a boost on the posterior fossa/tumor bed up to 54 Gy, followed by cisplatin/carboplatin, lomustine, and vincristine for a maximum of eight courses. Five of six diagnostic revised MRI were suggestive of the WNT molecular subgroup typical aspects. Methylation profile score (in two cases) and copy number variation analysis (chromosome 6 deletion in two cases) performed on four of six retrieved samples confirmed WNT molecular subgroup. Four out of six patients had a positive family history of FAP, while gastrointestinal symptoms prompted its identification in the other two cases. Four patients developed other tumors (desmoid, MELTUMP, melanoma, pancreatoblastoma, thyroid Tir3) from 5 to 7 years after MBL. Discussion Our data confirm a good prognosis for patients with MBL associated with FAP. Patients' secondary tumors may or may not be related to their syndrome or treatment, but warrant adequate attention when planning shared guidelines for these patients.

An expert consensus panel convened by the Italian Association for Inherited and Familial Gastrointestinal Tumors (Associazione Italiana per lo Studio della Familiarita ed Ereditarieta dei Tumori Gastrointestinali, AIFEG) reviewed the literature and agreed on a number of position statements regarding the definition and management of polyposis coli without an identified pathogenic mutation on the APC or MUTYH genes, defined in the document as NAMP (non-APC/MUTYH polyposis).

Introduction. Mutations of the APC (adenomatous polyposis coli) gene correlate mainly with familial adenomatous polyposis (FAP), but can occasionally be pathogenic for medulloblastoma (MBL) WNT subtype as well, the course of which has only recently been described. Methods. We retrospectively retrieved all patients with documented germline APC mutations and a centrally-reviewed diagnosis of MBL to examine the outcome of their MBL, late effects of its treatment, and further oncological events. Results. Between 2007-2016 we diagnosed and treated 6 patients, all with a pathogenic APC variant mutation, who all had MBL, classic histotype. None had metastatic disease. All patients were in complete remission a median 65 months after treatment with craniospinal irradiation at 23.4 Gy, plus a boost on the posterior fossa/tumor bed up to 54 Gy, followed by cisplatin/carboplatin, lomustine and vincristine for a maximum of 8 courses. Five of 6 diagnostic revised MRI were suggestive of the WNT molecular subgroup typical aspects. Four of 6 patients had a positive family history of FAP, while gastrointestinal symptoms prompted its identification in the other 2 cases. Four patients had developed other tumors (desmoid, MELTUMP, melanoma, pancreatoblastoma, thyroid Tir3) from 5 to 7 years after MBL. Discussion. Our data confirm a good prognosis for patients with MBL associated with FAP. Patients’ secondary tumors may or may not be related to their syndrome or treatment, but warrant adequate attention when planning shared guidelines for these patients.

Background: The best surgical choice for patients with familial adenomatous polyposis (FAP) is still debated. No prospective trials have been carried out to evaluate the pros and cons of the recommended procedures: total colectomy (ileorectal anastomosis [IRA]) vs restorative proctocolectomy (ileal pouch–anal anastomosis [IPAA]). The aim of this study was to provide a basis for tailored precision surgery in patients with FAP. Methods: We conducted a retrospective review of patients with FAP who underwent surgery and were registered in a dedicated database in Milan, Italy. Twenty-year survival related to surgical approach and prognostic factors were investigated using a Cox regression model. Results: A total of 925 patients underwent surgery between 1947 and 2015: 340 (36.8%) IPAA and 585 (63.2%) IRA. Colorectal cancer (CRC) at surgery was diagnosed in 28.6% of patients and a pathogenic APC variant was identified in 88%. During a median follow-up of 129 months, 150 patients died. The survival probability was significantly higher in the IRA than the IPAA group: 0.82 vs 0.75 (hazard ratio [HR] 0.6, 95% confidence interval [CI] 0.42–0.84). Multivariable regression modeling adjusted for propensity scores showed a similar difference, although no longer significant. Multivariable analysis indicated as independent risk factors CRC (HR 4.68, 95% CI 3.04–7.20) and age at surgery (HR 1.03, 95% CI 1.02–1.06). Among patients without cancer, the main risk factor for shorter survival was older age (HR 1.06, 95% CI 1.04–1.09). Conclusion: The study confirms excellent long-term results of surgical approaches with IRA and IPAA, suggesting that the best surgical choice may be an individually and clinically tailored approach, preferably at a young age.

Simple Summary Prophylactic total colectomy with ileo-rectal anastomosis (IRA) is the surgical approach that guarantees a better quality of life compared to proctocolectomy and ileo-anal anastomosis (IPAA) in familial adenomatous polyposis (FAP) patients. However, previous studies have warned about the high risk of cancer of the rectal stump, especially considering the young age of these patients. This is a retrospective study whose aim was to assess both clinical and surgical features of patients who developed cancer of the rectal stump. The data reported show that IRA is a safe approach from an oncological perspective. Since early tumors of the rectal stump may be easily detected via endoscopic or minimally invasive approaches, strict surveillance is necessary. Abstract Background: The balance between quality of life and colorectal cancer risk in familial adenomatous polyposis (FAP) patients is of primary importance. A cut-off of less than 30 polyps under 1 cm of diameter in the rectum has been used as an indication for performing ileo-rectal anastomosis (IRA) in terms of lower rectal cancer risk. This study aimed to assess clinical and surgical features of FAP patients who developed cancer of the rectal stump. Methods: This retrospective study included all FAP patients who underwent total colectomy/IRA from 1977 to 2021 and developed subsequent rectal cancer. Patients’ features were reported using descriptive statistics by considering the overall case series and within pre-specified classes of age (30 years) at first surgery. Results: Among the 715 FAP patients, 47 (6.57%, 95% confidence interval: 4.87; 8.65) developed cancer in the rectal stump during follow-up. In total, 57.45% of the population were male and 38.30% were proband. The median interval between surgery and the occurrence of rectal cancer was 13 years. This interval was wider in the youngest group (p-value: 0.012) than the oldest ones. Twelve patients (25.53%) received an endoscopic or minimally invasive resection. Amongst them, 61.70% were Dukes stage A cancers. Conclusions: There is a definite risk of rectal cancer after total colectomy/IRA; however, the time interval from the index procedure to cancer developing is long. Minimally invasive and endoscopic treatments should be the procedures of choice in patients with early stage cancers.

Background APC gene pathogenic variants are characterized by a lifetime risk of nearly 100% to develop a colorectal carcinoma. International guidelines suggest a prophylactic surgery in the second decade. Methods A descriptive analysis was performed evaluating a surgical series of adolescent patients with familial adenomatous polyposis (FAP) enrolled in the prospectively maintained hereditary polyposis registry. Results Thirty-eight adolescent patients (median age 16 years; range, 7-19) underwent laparoscopic prophylactic surgery. APC gene pathogenic variants were detected in all patients, and six patients were proband. No patients were converted to open surgery. Median postoperative stay was five days (4-16). Early postoperative complications were one dural puncture and one anastomotic leakage. Regarding late complications, we observed one patient having small bowel obstruction 56 months after surgery. Pathological reports showed one patient with pTis adenocarcinoma in two separate sites; 33 patients with low-grade dysplasia, four with high-grade dysplasia. One patient developed a desmoid tumor 37 months after surgery. After a median follow-up of 40.5 months, no patients died or had a second abdominal surgery because of cancer in rectal stump. Conclusions Rectal sparing surgery was the first choice in the major respect of patients' quality of life. Laparoscopic prophylactic surgery for FAP is well accepted from adolescents. It represents a safe option due to the low incidence of post-surgical desmoids and quick postoperative recovery.

International audience; The TurLab facility is a laboratory, equipped with a 5 m diameter and 1 m depth rotating tank, located in the Physics Department of the University of Turin. Originally, it was mainly built to study systems of different scales where rotation plays a key role in the fluid behaviour such as in atmospheric and oceanic flows. In the past few years the TurLab facility has been used to perform experiments related to the observation of Extreme Energy Cosmic Rays (EECRs) from space using the fluorescence technique. For example, in the case of the JEM-EUSO mission, where the diffuse night brightness and artificial light sources can vary significantly in time and space inside the Field of View of the telescope. The Focal Surface of Mini-EUSO Engineering Model (Mini-EUSO EM) with the level 1 (L1) and 2 (L2) trigger logics implemented in the Photo-Detector Module (PDM) has been tested at TurLab. Tests related to the possibility of using an EUSO-like detector for other type of applications such as Space Debris (SD) monitoring and imaging detector have also been pursued. The tests and results obtained within the EUSO@TurLab Project on these different topics are presented.

Introduction: Recent advances in technology and research are rapidly changing the diagnostic approach to hereditary gastrointestinal cancer (HGIC) syndromes. Although the practice of clinical genetics is currently transitioning from targeted criteria-based testing to multigene panels, important challenges remain to be addressed. The aim of this study was to develop and technically validate the performance of a multigene panel for HGIC. Methods: CGT-colon-G14 is an amplicon-based panel designed to detect single nucleotide variants and small insertions/deletions in 14 well-established or presumed high-penetrance genes involved in HGIC. The assay parameters tested were sensitivity, specificity, accuracy, and inter-run and intra-run reproducibility. Performance and clinical impact were determined using 48 samples of patients with suspected HGIC/polyposis previously tested with the targeted approach. Results: The CGT-colon-G14 panel showed 99.99% accuracy and 100% inter- and intra-run reproducibility. Moreover, panel testing detected 1 actionable pathogenic variant and 16 variants with uncertain clinical impact that were missed by the conventional approach because they were located in genes not previously analyzed. Conclusion: Introduction of the CGT-colon-G14 panel into the clinic could provide a higher diagnostic yield than a step-wise approach; however, results may not always be straightforward without the implementation of new genetic counseling models.

The PAMELA experiment has measured cosmic ray particles and antiparticles fluxes at Earth orbit from June 2006 till January 2016 onboard the Resurs-DK1 satellite. Measurements were carried out during the solar minimum of 23 solar cycle with negative polarity A < 0 of heliospheric magnetic field till the beginning of 24 cycle with positive polarity A > 0. In this paper, the results of observations of electron and positron fluxes are presented in wide energy range from several hundreds MeVs till several TeVs These measurements provide important information to study cosmic ray sources and propagation in Galaxy and heliosphere.

Patients with familial adenomatous polyposis (FAP) depend on a lifelong endoscopic surveillance programme and prophylactic surgery, and usually suffer nutritional problems. Intestinal inflammation has been linked to both FAP and colorectal cancer. Epidemiological studies show a relationship between diet and inflammation. Preventive dietary recommendations for FAP patients are so far lacking. We have designed a nonrandomized prospective pilot study on FAP patients to assess whether a low-inflammatory diet based on the Mediterranean diet principles and recipes, by interacting with the microbiota, reduces gastrointestinal markers of inflammation and improves quality of life. This report describes the scientific protocol of the study and reports the participants’ adherence to the proposed dietary recommendations. Thirty-four FAP patients older than 18 years, bearing the APC pathogenic variant, who underwent prophylactic total colectomy with ileo-rectal anastomosis were eligible into the study. During the 3-month dietary intervention, they reported improvements in their consumption of Mediterranean foods (vegetables, fruits, fish, and legumes), and a reduction in pro-inflammatory foods (red/processed meat and sweets); this led to a significant increase in their adherence to the Mediterranean diet. The improvement was accompanied by a decrease in the number of diarrhoeal discharges. These preliminary results are encouraging with regard to feasibility, dietary outcome measures, and safety.

The Probe Of Extreme Multi-Messenger Astrophysics (POEMMA) is designed to observe cosmic neutrinos (CNs) above 20 PeV and ultra-high energy cosmic rays (UHECRs) above 20 EeV over the full sky. The POEMMA mission calls for two identical satellites flying in loose formation, each comprised of a 4-meter wide field-of-view (45 degrees) Schmidt photometer. The hybrid focal surface includes a fast (1 ${\mu}$s) ultraviolet camera for fluorescence observations and an ultrafast (10 ns) optical camera for Cherenkov observations. POEMMA will provide new multi-messenger windows onto the most energetic events in the universe, enabling the study of new astrophysics and particle physics at these otherwise inaccessible energies., Comment: 8 pages, 6 figures, presented in 36th International Cosmic Ray Conference (Madison). arXiv admin note: substantial text overlap with arXiv:1907.06217

Mini-EUSO is a UV telescope that will look downwards to the Earth's atmosphere onboard the International Space Station. With the design of the ultra-high energy cosmic ray fluorescence detectors belonging to the JEM-EUSO program, it will make the first UV map of the Earth by observing atmospheric phenomena such as transient luminous events, sprites and lightning, as well as meteors and bioluminescence from earth. Diffused light from laser shots from the ground, which mimic the fluorescence light emitted by Nitrogen molecules when extensive air showers pass through the atmosphere, can be used to verify the capability of this kind of detector to observe ultra-high energy cosmic rays. To validate the electronics and the trigger algorithms developed for Mini-EUSO, a scaled down version of the telescope with 1:9 of the original focal surface and a lens of 2.5 cm diameter has been built. Tests of the Mini-EUSO engineering model have been made in laboratory and in open sky condition. In this paper, we report results of observations of the night sky, which include the detection of stars, meteors, a planet and a rocket body reflecting the sunlight. Interesting results of the observation of city lights are also reported., Comment: presented at the 36th ICRC (Madison, WI; 2019)

Objective: To investigate the performance of tumor testing approaches in the identification of Lynch syndrome (LS) in a single-center cohort of people with colorectal cancer (CRC). Methods: A retrospective analysis of data stored in a dedicated database was carried out to identify patients with CRC suspected for LS who were referred to Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, between 1999 and 2014. The sensitivity and specificity of immunohistochemistry (IHC) for mismatch repair (MMR) proteins and microsatellite instability (MSI) analysis (alone or combined) were calculated with respect to the presence of causative MMR germline variants. Results: A total of 683 patients with CRC suspected for LS were identified. IHC results of MMR protein analysis and MSI were assessed in 593 and 525 CRCs, respectively, while germline analysis was performed in 418 patients based on the IHC or MSI test result and/or clinical features. Univariate and multivariate analysis revealed a significant correlation of pathogenic MMR germline variants with all clinicopathologic features including Amsterdam criteria, presence of endometrial cancer, CRC site, age at onset, stage, and grade. The highest odds ratio values were observed for IHC and MSI (17.1 and 8.8, respectively). The receiver operating characteristic curve and area under the curve values demonstrated that IHC alone or combined with other clinicopathologic parameters was an excellent test for LS identification. Conclusions: This study confirms the effectiveness of tumor testing to identify LS among patients with CRC. Although IHC and MSI analysis were similarly effective, IHC could be a better strategy for LS identification as it is less expensive and more feasible.

The PAMELA experiment has been collecting data since 2006; its results indicate a rise in the positron fraction with respect to the sum of electrons and positrons in the cosmic-ray (CR) spectrum above 10 GeV. This excess can be due to additional sources, as SNRs or pulsars, which can lead to an anisotropy in the local CR positron, detectable from current experiments. We report on the analysis on spatial distributions of positron events collected by PAMELA, taking into account also the geomagnetic field effects. No significant deviation from the isotropy has been observed.

The last solar cycle has presented a peculiarly long quiet phase with consequent minimum modulation conditions for cosmic rays. The proton and electron spectra were measured from July 2006 to December 2009 by PAMELA experiment, providing fundamental information about the transport and modulation of cosmic rays inside the heliosphere. These studies allow to obtain a more complete description of the cosmic radiation. In this picture the time dependence of the helium spectrum become very important to constrain parameters of the actual solar modulation model. The crucial point for this analysis is the selection of a dataset of helium events which ensure high statistics with a very low contamination. In this paper the definition of the selection criteria for helium events with data taken from July 2006 to June 2014 by PAMELA experiment is reported.

We present a measurements of electron and positron fluxes below the geomagnetic cutoff rigidity in wide energy range from ~50 MeV to several GeVs by the PAMELA magnetic spectrometer. The instrument was launched on June 15th 2006 on-board the Resurs-DK satellite on low orbit with 70 degrees inclination and altitude between 350 and 600 km. Features of spatial distributions of secondary electrons and positrons in the near Earth space, including the South Atlantic Anomaly, were investigated in terms of lifetime and geographical origin. The separation in stably trapped , long lifetime quasi-trapped, and short lifetime albedo components was performed on base of back tracing procedure in geomagnetic field. A significant difference in relative abundance of positrons with respect to electrons is seen for the stable trapped and the quasi-trapped populations what pointing out on different trapping mechanism of those populations.

Familial adenomatous polyposis is a Mendelian syndrome in which germline loss-of-function mutations of APC are associated with multiple adenomatous polyps of the large bowel, a multiplicity of extracolonic features, and a high lifetime risk of colorectal cancer. Different APC germline mutations have been identified, including sequence changes, genomic rearrangements, and expression defects. Recently, very rare families have been associated with constitutive large deletions encompassing the APC-5' regulatory region, while leaving the remaining gene sequence intact; the regulatory region contains a proximal and a distal promoter, called 1A and 1B, respectively. We identified a novel deletion encompassing promoter 1B in a large Italian family that manifested polyposis in three of the six branches descending from a founding couple married in 1797. By combining different molecular approaches on both DNA and RNA, we precisely mapped this deletion (6,858 bp in length) that proved to be associated with APC allele silencing. The finding of the same deletion in two additional polyposis families pointed to a founder mutation in Italy. Deletion carriers from the three families all showed a “classical” polyposis phenotype. To explore the molecular mechanisms underlying promoter deletions, we performed an in silico analysis of the breakpoints of 1A and 1B rearrangements so far reported in the literature; moreover, to decipher genotype-phenotype correlations, we critically reviewed current knowledge on deletions vs. point mutations in the APC-5' regulatory region. This article is protected by copyright. All rights reserved.

Magnetic spectrometer PAMELA was launched onboard a satellite Resurs-DK1 into low-Earth polar orbit with altitude 350-600 km to study cosmic ray antiparticle fluxes in a wide energy range from ~ 100 MeV to hundreds GeV. This paper presents the results of observations of temporal variations of the positron and electron fluxes in the 2006-2015. The ratio of the positron and electron fluxes below 2 GV shows sharp increasing since 2014 due to changing of the polarity of the solar magnetic field.

Solar modulation of galactic protons with energies from 50 MeV up to dozens of GeV during July '06 - January '16 studied based on a data of the magnetic spectrometer PAMELA and scintillation spectrometer ARINA. This period is interesting because it covers the end of 23rd and current 24th cycles of solar activity, including the abnormally long transient period and change of the polarity of solar magnetic field. © Published under licence by IOP Publishing Ltd.

To determine prevalence, spectrum and genotype-phenotype correlations of MUTYH variants in Italian patients with suspected MAP (MUTYH-associated polyposis), a retrospective analysis was conducted to identify patients who had undergone MUTYH genetic testing from September 2002 to February 2014. Results of genetic testing and patient clinical characteristics were collected (gender, number of polyps, age at polyp diagnosis, presence of colorectal cancer (CRC) and/or other cancers, family data). The presence of large rearrangements of the MUTYH gene was evaluated by Multiplex Ligation-dependent Probe Amplification analysis. In all, 299 patients with colorectal neoplasia were evaluated: 61.2% were males, the median age at polyps or cancer diagnosis was 50 years (16-80 years), 65.2% had

The PAMELA detector was launched on June 15 th of 2006 on board the Russian Resurs-DK1 satellite and during ten years of continuous data-taking it has observed very interesting features in cosmic rays, especially in the fluxes of protons, helium and electrons. Moreover, PAMELA measurements of cosmic antiproton and positron fluxes and positron-to-all-electron ratio have set strong constraints to the nature of Dark Matter. Measurements of boron, carbon, lithium and beryllium (together with the isotopic fraction) have also shed new light on the elemental composition of the cosmic radiation. Search for signatures of more exotic processes (such as the ones involving Strange Quark Matter) has also been pursued. Furthermore, over the years the instrument has allowed a constant monitoring of the solar activity and a prolonged study of the solar modulation, improving the comprehension of the heliosphere mechanisms. PAMELA has also measured the radiation environment around the Earth, and detected for the first time the presence of an antiproton radiation belt surrounding our planet. In this highlight paper PAMELA main results will be reviewed.

The large-scale anisotropy (or the so-called star-diurnal wave) has been studied using the calorimeter of the space-born experiment PAMELA. The cosmic ray anisotropy has been obtained for the Southern and Northern hemispheres simultaneously in the equatorial coordinate system for the time period 2006–2014. The dipole amplitude and phase have been measured for energies 1–20 TeV n-1.

Data from the PAMELA satellite experiment were used to measure the geomagnetic cutoff for high-energy ( 80 MeV) protons during the solar particle events on 2006 December 13 and 14. The variations o ...

The PAMELA cosmic ray detector was launched on June 15th of 2006 on board the Russian Resurs-DK1 satellite and during nine years of continuous data-taking it has ob- served very interesting feature ...