Multigene panel testing in Hereditary Breast and Ovarian Cancer: an effective liquid biopsy approach to identify mutations in genes involved in the Homologous Recombination pathway

Background: Hereditary breast and ovarian cancer (HBOC) syndrome is an autosomal dominant inherited disorder that include 5–7% of all breast cancer (BC) cases and 10-15% of all ovarian cancer (OC) cases. BRCA1 and BRCA2 are the most common genes associated to HBOC syndrome. However, hereditary syndrome could be associated with germline PVs in several high- and moderate-risk genes. In recent years, Next-Generation Sequencing (NGS) has allowed to study multiple genes simultaneously, to reduce analysis costs, to led to an explosion of genetic data, and to offer more information to patients. Methods: We retrospectively collected and analyzed to BRCA1/2 test 876 patients affected by BC and OC (531 of BC, 345 of OC) among January 2016 to August 2020. Successively, we analyzed 192 patients resulted BRCA1/2 negative with a strong personal and/or family history to BC and/or OC by using Multi-gene panel testing. We evaluated 22 genes involved in risk of hereditary breast, ovarian and colorectal cancer, and other inherited tumor syndromes. Results: Analysis conducted with multi-gene panel testing revealed that 28 (14.6%) BC and OC patients showed PVs/LPVs in genes no-BRCA. In particular, we analyzed 165 BC patients and 27 OC patients, and we obtained 27 and 4 patients with PVs/LPVs in genes no-BRCA respectively. BC patients with alteration in gene over BRCA hardly showed TNBC than patients with BRCA1/2 or all wt. Moreover, among BC patients with genes altered beyond BRCA the 45.8% showed a Bilateral Breast Cancer. In OC group we observed that 75% of patients with PVs/LPVs in genes over BRCA showed a previously personal history of BC or other cancer. Conclusion: Our analysis showed that the 14.6% of patients BRCA-negative with a strong personal and/or family history to BC and/or OC presented alteration in genes beyond BRCA1/2. This result highlighted the importance of multi-gene panel testing which should be extended at all these patients and be included in clinical practic

Intrafamily Resource Allocations: A Dynamic Model of Birth Weight

This paper estimates a model of dynamic intrahousehold investment behavior which incorporates family fixed effects and child endowment heterogeneity. This framework is applied to large American and British survey data on birth outcomes, with focus on the effects of antenatal parental smoking and maternal labor supply net of other maternal behavior and child characteristics. We find that maternal smoking during pregnancy reduces birth weight and fetal growth, while paternal smoking has virtually no effect. Mothers' work interruptions of up to two months before birth have a positive effect on birth outcomes, especially among British children. Parental behavior appears to respond to permanent family-specific unobservables and to child idiosyncratic endowments in a way that suggests that parents have equal concerns, rather than efficiency motives, in allocating their prenatal inputs across children. Evidence of equal concerns emerges also from the analysis of breastfeeding decisions, although the effects in this case are weaker.birth outcomes, smoking, mother's work, sibling estimators, instrumental variables, child health production functions

Trait-oriented Programming in Java 8

International audienceJava 8 was released recently. Along with lambda expressions, a new language construct is introduced: default methods in interfaces. The intent of this feature is to allow interfaces to be extended over time preserving backward compatibility. In this paper, we show a possible, different use of interfaces with default methods: we introduce a trait-oriented programming style based on an interface-as- trait idea, with the aim of improving code modularity. Starting from the most common operators on traits, we introduce some programming patterns mimicking such operators and discuss this approach

Health Information and Health Outcomes: An Application of the Regression Discontinuity Design to the 1995 UK Contraceptive Pill Scare Case

This paper provides a general formulation of the regression discontinuity (RD) design and shows its general applicability to many epidemiological problems. It then applies the RD method to estimate the effects of the 1995 pill scare in the UK, using individual birth records and aggregate monthly statistics. The results show that, following the announce- ment of the health warning on the þird generation" pill, conception rates increased by about 7%, with a 9% increase in abortion rates and a 6-7% rise in birth rates. No e®ect was found on still births, very low birth weight, sex ratios, or average birth weight. There is evidence of a slight increase in the rates of low birth weight births and multiple births and of a considerable reduction in the rate of births with congenital anomalies. Hetero- geneity by mother's age and social class is very pronounced, with most of the e®ects being experienced by women aged less than 25 and of lower socioeconomic status

On the use of asymmetric PSF on NIR images of crowded stellar fields

We present data collected using the camera PISCES coupled with the Firt Light Adaptive Optics (FLAO) mounted at the Large Binocular Telescope (LBT). The images were collected using two natural guide stars with an apparent magnitude of R<13 mag. During these observations the seeing was on average ~0.9". The AO performed very well: the images display a mean FWHM of 0.05 arcsec and of 0.06 arcsec in the J- and in the Ks-band, respectively. The Strehl ratio on the quoted images reaches 13-30% (J) and 50-65% (Ks), in the off and in the central pointings respectively. On the basis of this sample we have reached a J-band limiting magnitude of ~22.5 mag and the deepest Ks-band limiting magnitude ever obtained in a crowded stellar field: Ks~23 mag. J-band images display a complex change in the shape of the PSF when moving at larger radial distances from the natural guide star. In particular, the stellar images become more elongated in approaching the corners of the J-band images whereas the Ks-band images are more uniform. We discuss in detail the strategy used to perform accurate and deep photometry in these very challenging images. In particular we will focus our attention on the use of an updated version of ROMAFOT based on asymmetric and analytical Point Spread Functions. The quality of the photometry allowed us to properly identify a feature that clearly shows up in NIR bands: the main sequence knee (MSK). The MSK is independent of the evolutionary age, therefore the difference in magnitude with the canonical clock to constrain the cluster age, the main sequence turn off (MSTO), provides an estimate of the absolute age of the cluster. The key advantage of this new approach is that the error decreases by a factor of two when compared with the classical one. Combining ground-based Ks with space F606W photometry, we estimate the absolute age of M15 to be 13.70+-0.80 Gyr.Comment: 15 pages, 7 figures, presented at the SPIE conference 201

Nel laboratorio di Pirandello. Spigolando tra i "Taccuini".

La Tesi di Dottorato ha per oggetto tre Taccuini di Pirandello, studiati sia sul versante filologico che su quello ermeneutico. Si tratta del Taccuino Segreto (edito dalla Mondadori nel 1997 a cura di Annamaria Andreoli), del Taccuino di Harvard (edito dalla Mondadori nel 2002 a cura di Ombretta Frau e Cristina Gragnani) e del Taccuino di Coazze (edito in copia anastatica dalla Biblioteca-Museo “Luigi Pirandello di Agrigento” nel 1998 e nel 2001). Se l’edizione critica che correda il saggio intende operare una revisione filologica dei tre documenti, con un riesame delle concordanze dei primi due Taccuini e una prima edizione critica del testo e delle concordanze del Taccuino di Coazze, l’ampio saggio introduttivo (diviso in tre parti dedicate ai rispettivi Taccuini) ha lo scopo di operare la sintesi su quanto sinora scritto in merito al “laboratorio di Pirandello”, sviluppando quanto emerso dallo studio filologico ed ermeneutico.The object of this Doctorate’s thesis are three Pirandello’s Notebooks: Taccuino segreto (ed. by Annamaria Andreoli, Mondadori Milano 1997), Taccuino di Harvard (ed. by Ombretta Frau and Cristina Gragnani, Mondadori, Milano 2002), Taccuino di Coazze (printed by “Biblioteca-Museo Luigi Pirandello” Agrigento). The Critical edition’s purpose is a philological study of Pirandello’s Notebooks, with concordance’s review of Segreto and Harvard’s Notebooks, and first study of Coazze’s Notebook (philological edition and concordance). The Essay analyzes “Pirandello’s Laboratory”, when until now studied in essays and articles of “Pirandello’s “laboratory” and “style”, and considerations of our study and our philological edition

Understanding the SES Gradient in Early Child Development: Maternal Work, Home Learning, and Child Care Decisions

This paper examines the impacts of family inputs | i.e., maternal employment, child care and home learning | on the early development of British children. Using rich longitudinal data from the UK Millennium Cohort Study we estimate cognitive and non-cognitive achievement production functions that allow outcomes to depend on the history of family inputs and unobserved child endowments. We find evidence of small effects on early child outcomes of all the family inputs under consideration. Nonetheless, according to some models, family inputs are found to reduce socioeconomic status inequalities in early child development quite substantially, while according to other models they are found to magnify them. Attempting to equalize child outcomes through early policy interventions that generically affect family inputs may therefore prove difficult

Early Maternal Time Investment and Early Child Outcomes

Using large longitudinal survey data from the UK Millennium Cohort Study, this paper estimates the effec of maternal time inputs on early child development. We find that maternal time is a quantitatively important determinant of skill formation and that its effect declines with child age. There is evidence of a long shadow of the effect of early maternal time inputs on later outcomes, especially in the cas of cognitive skill develpment. In the case of non-cognitive develpment, this effect disappears when we account for skill persistance