Guido Calabresi on Torts: Italian Courts and the Cheapest Cost Avoider

Guido Calabresi proposed to replace the dominating paradigm of fault with simpler strict liability rules that put liability on the most appropriate actors (the cheapest cost avoiders). Assuming that the objective function of the tort system is the mimimization of the sum of the injury and injury avoidance costs associated with accidents (primary costs), risk-spreading costs (secondary costs), and administrative costs (tertiary costs), he suggested that the adoption of strict liability, targeted to specified activities, would achieve the goal of cost minimization. The core of an extremely richer message was that the cheapest cost avoider test would abate the administrative costs of courts. Moreover, the manufacturers' ability to spread the costs of strict liability through the prices charged for their products would effectively insure product users against the risks of injury. This masterpiece of normative analysis has deployed an ever increasing influence on thinking about tort law, not only in the US but also in Europe. This paper aims to trace the impact of Calabresi's ideas on Italian case-law. After a brief introduction, section 2 outlines the methodology adopted in the research. The following sections, 3 to 13, present (and cursorily comment on) the opinions which display the influence of Calabresi's thinking. Section 14 summarizes and concludes

Role of bound pairs in the optical properties of highly excited semiconductors: a self consistent ladder approximation approach

Presence of bound pairs (excitons) in a low-temperature electron-hole plasma is accounted for by including correlation between fermions at the ladder level. Using a simplified one-dimensional model with on-site Coulomb interaction, we calculate the one-particle self-energies, chemical potential, and optical response. The results are compared to those obtained in the Born approximation, which does not account for bound pairs. In the self-consistent ladder approximation the self-energy and spectral function show a characteristic correlation peak at the exciton energy for low temperature and density. In this regime the Born approximation overestimates the chemical potential. Provided the appropriate vertex correction in the interaction with the photon is included, both ladder and Born approximations reproduce the excitonic and free pair optical absorption at low density, and the disappearance of the exciton absorption peak at larger density. However, lineshapes and energy shifts with density of the absorption and photoluminescence peaks are drastically different. In particular, the photoluminescence emission peak is much more stable in the ladder approximation. At low temperature and density a sizeable optical gain is produced in both approximations just below the excitonic peak, however this gain shows unphysical features in the Born approximation. We conclude that at low density and temperature it is fundamental to take into account the existence of bound pairs in the electron-hole plasma for the calculation of its optical and thermodynamic properties. Other approximations that fail to do so are intrinsically unphysical in this regime, and for example are not suitable to address the problem of excitonic lasing.Comment: 14 pages, 12 figure

Developmental profiles of infants with an FMR1 premutation

Abstract Background Emerging evidence suggests that a subset of FMR1 premutation carriers is at an increased risk for cognitive, emotional, and medical conditions. However, because the premutation is rarely diagnosed at birth, the early developmental trajectories of children with a premutation are not known. Methods This exploratory study examined the cognitive, communication, and social-behavioral profiles of 26 infants with a premutation who were identified through participation in a newborn screening for fragile X syndrome pilot study. In this study, families whose newborn screened positive for an FMR1 premutation were invited to participate in a longitudinal study of early development. Twenty-six infants with the premutation and 21 matched, screen-negative comparison babies were assessed using validated standardized measures at 6-month intervals starting as young as 3 months of age. The babies were assessed up to seven times over a 4-year period. Results The premutation group was not statistically different from the comparison group on measures of cognitive development, adaptive behavior, temperament, or overall communication. However, the babies with the premutation had a significantly different developmental trajectory on measures of nonverbal communication and hyperresponsivity to sensory experiences. They also were significantly more hyporesponsive at all ages than the comparison group. Cytosine-guanine-guanine repeat length was linearly associated with overall cognitive development. Conclusions These results suggest that infants with a premutation may present with subtle developmental differences as young as 12 months of age that may be early markers of later anxiety, social deficits, or other challenges thought to be experienced by a subset of carriers

Global increases in both common and rare copy number load associated with autism.

Children with autism have an elevated frequency of large, rare copy number variants (CNVs). However, the global load of deletions or duplications, per se, and their size, location and relationship to clinical manifestations of autism have not been documented. We examined CNV data from 516 individuals with autism or typical development from the population-based Childhood Autism Risks from Genetics and Environment (CHARGE) study. We interrogated 120 regions flanked by segmental duplications (genomic hotspots) for events >50 kbp and the entire genomic backbone for variants >300 kbp using a custom targeted DNA microarray. This analysis was complemented by a separate study of five highly dynamic hotspots associated with autism or developmental delay syndromes, using a finely tiled array platform (>1 kbp) in 142 children matched for gender and ethnicity. In both studies, a significant increase in the number of base pairs of duplication, but not deletion, was associated with autism. Significantly elevated levels of CNV load remained after the removal of rare and likely pathogenic events. Further, the entire CNV load detected with the finely tiled array was contributed by common variants. The impact of this variation was assessed by examining the correlation of clinical outcomes with CNV load. The level of personal and social skills, measured by Vineland Adaptive Behavior Scales, negatively correlated (Spearman's r = -0.13, P = 0.034) with the duplication CNV load for the affected children; the strongest association was found for communication (P = 0.048) and socialization (P = 0.022) scores. We propose that CNV load, predominantly increased genomic base pairs of duplication, predisposes to autism

Testing the FMR1 Promoter for Mosaicism in DNA Methylation among CpG Sites, Strands, and Cells in FMR1-Expressing Males with Fragile X Syndrome

Variability among individuals in the severity of fragile X syndrome (FXS) is influenced by epigenetic methylation mosaicism, which may also be common in other complex disorders. The epigenetic signal of dense promoter DNA methylation is usually associated with gene silencing, as was initially reported for FMR1 alleles in individuals with FXS. A paradox arose when significant levels of FMR1 mRNA were reported for some males with FXS who had been reported to have predominately methylated alleles. We have used hairpin-bisufite PCR, validated with molecular batch-stamps and barcodes, to collect and assess double-stranded DNA methylation patterns from these previously studied males. These patterns enable us to distinguish among three possible forms of methylation mosaicism, any one of which could explain FMR1 expression in these males. Our data indicate that cryptic inter-cell mosaicism in DNA methylation can account for the presence of FMR1 mRNA in some individuals with FXS

Renal function is impaired in normotensive chronic HCV patients: role of insulin resistance

Renal dysfunction is an independent predictor for cardiovascular morbidity and mortality. We investigated whether chronic hepatitis C virus (HCV) infection and the related insulin resistance/hyperinsulinemia influence renal function in comparison with a group of healthy subjects and with another group with metabolic syndrome. We enrolled 130 newly diagnosed HCV outpatients matched for age and gender with 130 patients with metabolic syndrome and 130 healthy subjects. Renal function was evaluated by calculation of glomerular filtration rate (e-GFR, mL/min/1.73 m2) using the CKD-EPI equation. The following laboratory parameters were measured: fasting plasma glucose and insulin, total, LDL- and HDL-cholesterol, triglyceride, creatinine, and HOMA to evaluate insulin sensitivity. HCV patients with respect to both healthy subjects and metabolic syndrome patients have a decreased e-GFR: 86.6 ± 16.1 vs 120.2 ± 23.1 mL/min/1.73 m2 (P < 0.0001) and 94.9 ± 22.6 mL/min/1.73 m2 (P = 0.003), respectively. Regarding biochemical variables, HCV patients, in comparison with healthy subjects, have a higher triglyceride level, creatinine, fasting insulin and HOMA (3.4 ± 1.4 vs 2.6 ± 1.3; P < 0.0001). At linear regression analysis, the correlation between e-GFR and HOMA is similar in the metabolic syndrome (r = -0.555, P < 0.0001) and HCV (r = -0.527, P < 0.0001) groups. At multiple regression analysis, HOMA is the major determinant of e-GFR in both groups, accounting for, respectively, 30.8 and 27.8 % of its variation in the metabolic syndrome and HCV. In conclusion, we demonstrate that HCV patients have a significant reduction of e-GFR and that insulin resistance is the major predictor of renal dysfunction

A Randomized Controlled Trial of Sertraline in Young Children With Autism Spectrum Disorder.

Objective: Selective serotonin reuptake inhibitors like sertraline have been shown in observational studies and anecdotal reports to improve language development in young children with fragile X syndrome (FXS). A previous controlled trial of sertraline in young children with FXS found significant improvement in expressive language development as measured by the Mullen Scales of Early Learning (MSEL) among those with comorbid autism spectrum disorder (ASD) in post hoc analysis, prompting the authors to probe whether sertraline is also indicated in nonsyndromic ASD. Methods: The authors evaluated the efficacy of 6 months of treatment with low-dose sertraline in a randomized, double-blind, placebo-controlled trial in 58 children with ASD aged 24 to 72 months. Results: 179 subjects were screened for eligibility, and 58 were randomized to sertraline (32) or placebo (26). Eight subjects from the sertraline arm and five from the placebo arm discontinued. Intent-to-treat analysis showed no significant difference from placebo on the primary outcomes (MSEL expressive language raw score and age equivalent combined score) or secondary outcomes. Sertraline was well tolerated, with no difference in side effects between sertraline and placebo groups. No serious adverse events possibly related to study treatment occurred. Conclusion: This randomized controlled trial of sertraline treatment showed no benefit with respect to primary or secondary outcome measures. For the 6-month period, treatment in young children with ASD appears safe, although the long-term side effects of low-dose sertraline in early childhood are unknown. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02385799

Fábrica Magnética y Microestructuras a través de los Andes de Tierra del Fuego, Argentina

An anisotropy of magnetic susceptibility (AMS) transect was carried out across the Fuegian Andes, in Argentina, withthe aim of studying its tectonic evolution. Two-hundred and forty oriented samples were collected from 27 sites distributed between the Paso Garibaldi to the north and the Canal Beagle to the south. The study was restricted to the Upper Jurassic Lemaire Formation, with a single site located in the Lower Cretaceous Yahgán Formation. Stu-died rocks comprised basaltic, andesitic, volcaniclastic and sedimentary rocks affected by low-grade metamorphism. AMS measurements were complemented with thin section analyses of representative samples in order to characterize the microstructures and metamorphic assemblages. In general, the magnetic fabric shows dominantoblate shapes and a large variation in the anisotropy degree from 1.04 up to 2. The anomalously high values were observed to be associa-ted to growth of secondary pyrrhotite, which was identified by rock magnetic tests. Magnetic foliation was generally consistent with slaty cleaveage as observed in the field, confirming the tectonic origin of the magnetic fabric. Three geographic domains were distinguished in the study región on the basis of the pattern of the AMS axes distribution. In the northern domain, from Paso Garibaldi to Valle Carbajal, the orientation of the máximum susceptibility axis (κ1), or magnetic lineation, is N-S to NE-SW with modérate plunge towards the S-SW and coincides with previous determination of mineral lineations associated with the Andean deformation and very low grade metamorphism. The magnetic fabric pattern can be correlated with the main deformational phase responsible for the development of slaty cleavage (main Andean deformational phase) and the tectonic transport due to progression of the Fuegian fold and thrust belt in the Late Cretaceous. A different character is shown along the Valle Carbajal domain, where subvertical E-W magnetic foliation planes and roughly E-W to ESE-WNW subhorizontal magnetic lineations are more difficult to correlate with the main folding phase and suggest its relation to an E-W, possibly localized, strike-slip regime during the main deformational and metamorphic phase. The magnetic fabrics in the third domain, cióse to the Canal Beagle, displays a more heterogeneous character with both E-W and N-S striking foliations; in this case a population of subhorizontal E-W magnetic lineation (κ1) suggests the existence of a significant component of strike-slip deformation. Se presentan los resultados de una transecta de Anisotropía de Susceptibilidad Magnética (ASM) realizada en los Andes Fueguinos, Argentina. Se midieron 240 muestras orientadas provenientes de 27 sitios de muestreo distribuidos entre Paso Garibaldi, al norte y el Canal Beagle al sur. El muestreo se focalizó esencialmente en la Formación Lemaire del Jurásico Superior, con un único sitio en la Formación Yahgán del Cretácico inferior. Las litologías estudiadas incluyen basaltos, andesitas y rocas volcanoclásticas y sedimentarias afectadas por metamorfismo de bajo grado. Las mediciones de fábrica magnética se complementaron con el estudio microscópico de muestras representativas con el propósito de caracterizar las microestructuras y las asociaciones metamórficas. La fábrica magnética está dominada por formas obladas y presenta una gran variación en el grado de anisotropía (1,04-2). Los mayores valores de anisotropía están asociados a la presencia de pirrotina secundaria, identificada por medio de ensayos magnéticos. La foliación magnética muestra muy buena correspondencia con el clivaje medido en campo, confirmando el origen tectónico de la fábrica magnética. Los modelos de distribución de los ejes de ASM permitieron distinguir tres dominios geográficos. El dominio septentrional, entre Paso Garibaldi y Valle Carbajal, presenta lineaciones magnéticas (κ1) de orientación N-S aNE-SW con buzamiento moderado hacia el S-SW, coincidente con determinaciones previas de lineaciones minerales asociadas con la deformación andina. Este diseño de fábrica magnética se vincula a la fase de deformación principal responsable del desarrollo del clivaje pizarreño y de la faja plegada y corrida Fueguina en el Cretácico Tardío. Un segundo dominio corresponde al Valle Carbajal, caracterizado por foliaciones magnéticas E-W, subverticales y lineaciones magnéticas E-W (a ESE-WNW) subhorizontales que se interpretan como vinculados a regímenes localizados de transcurrencia. La fábrica magnética en el tercer dominio, en la zona del Canal Beagle, presenta un carácter más heterogéneo con foliaciones de orientación tanto E-W como N-S; la presencia de una población de lineaciones magnéticas subhorizontales de rumbo E-W sugiere la existencia de un componente de rumbo significativo

Fragile X Newborn Screening: Lessons Learned From a Multisite Screening Study

BACKGROUND: Delays in the diagnosis of children with fragile X syndrome (FXS) suggest the possibility of newborn screening as a way to identify children earlier. However, FXS does not have a proven treatment that must be provided early, and ethical concerns have been raised about the detection of infants who are carriers. This article summarizes major findings from a multisite, prospective, longitudinal pilot screening study. METHODS: Investigators in North Carolina, California, and Illinois collaborated on a study in which voluntary screening for FXS was offered to parents in 3 birthing hospitals. FXS newborn screening was offered to >28 000 families to assess public acceptance and determine whether identification of babies resulted in any measurable harms or adverse events. Secondary goals were to determine the prevalence of FMR1 carrier gene expansions, study the consent process, and describe early development and behavior of identified children. RESULTS: A number of publications have resulted from the project. This article summarizes 10 "lessons learned" about the consent process, reasons for accepting and declining screening, development and evaluation of a decision aid, prevalence of carriers, father participation in consent, family follow-up, and maternal reactions to screening. CONCLUSIONS: The project documented public acceptance of screening as well as the challenges inherent in obtaining consent in the hospital shortly after birth. Collectively, the study provides answers to a number of questions that now set the stage for a next generation of research to determine the benefits of earlier identification for children and families

HSD17B7 gene in self-renewal and oncogenicity of keratinocytes from Black versus White populations.

Human populations of Black African ancestry have a relatively high risk of aggressive cancer types, including keratinocyte-derived squamous cell carcinomas (SCCs). We show that primary keratinocytes (HKCs) from Black African (Black) versus White Caucasian (White) individuals have on average higher oncogenic and self-renewal potential, which are inversely related to mitochondrial electron transfer chain activity and ATP and ROS production. HSD17B7 is the top-ranked differentially expressed gene in HKCs and Head/Neck SCCs from individuals of Black African versus Caucasian ancestries, with several ancestry-specific eQTLs linked to its expression. Mirroring the differences between Black and White HKCs, modulation of the gene, coding for an enzyme involved in sex steroid and cholesterol biosynthesis, determines HKC and SCC cell proliferation and oncogenicity as well as mitochondrial OXPHOS activity. Overall, the findings point to a targetable determinant of cancer susceptibility among different human populations, amenable to prevention and management of the disease