Dept. of letters and philosophy

This essay explores Bernard Williams’ notion of agent-regret, comparing it with guilt, remorse, and other forms of regret. I first highlight some features of the intentional structure of guilt (also in relation to shame) and remorse, and then proceed to the analysis of regret. I discuss several examples of regret, including Williams’ discussion of the truck driver who accidentally runs over a child. In agreement with Williams, I argue that agent-regret has a moral significance not captured by either guilt or remorse. If we generally feel guilty or remorseful for intentional actions or omissions, regret shows that we are emotionally attached even to the involuntary aspects of what we do. Agent-regret suggests that our concept of responsibility is broader than we think, and its phenomenology (as well as its potential action tendencies) may be indicative of an agent’s morality.

Gassendi and IjAffaire Galilge of the Laws of Motion* The Argument In t h e lively discussions on Galileo's laws of m o t i o n after the Pisan's death, we observe w h a t might be called a new "Galilean affair." T h a t is, a trial brought against his new science of m o t i o n mainly by French a n d Italian Jesuits with t h e substantial adherence of M. Mersenne. T h i s new trail was originated by Gassendi's presentation of Galileo's de motu not simply as a perfectly coherent doctrine, but also as a convincing argument in favor of the t r u t h of Copernicanism. Lhfluire GalilPe that I will be dealing with does not concern the condemnation of the Pisan scientist in 1633 and the reactions which this event produced in Europe. Even if for many reasons it still remains problematical, that uffaire has been the object of thorough studies, even recent ones, to which I have nothing new to add. There is, however, another Galilean ufluire that began immediately after the conclusion of the first, upon the death of Galileo in 1642. In this second episode the scandal was represented by the Galilean laws of motion, submitted to a series of severe censures between 1642 and 1648, especially in France. At the origin of the uffaire of the Galilean science of motion is the articulated presentation that Gassendi gave of it in the De motu impress0 a motore traslato published in 1642 (Gassendi 1642),1 but materially drafted in 1640, two years after the publication of Galileo's Two new sciences, that Gassendi had read with considerable attention. * This paper reproduces, with a few changes, the essay published in Italian in 1993 (Galluzzi 1993). Since then a few studies have been published which discuss the themes dealt with in this work, shedding new light on the protagonists of this capital discussion. Among these new contributions appear of special interest the long awaited critical edition of Baliani 's De mofu, edited by Giovanna Baroncelli, and the essay by Carla Rita Palmerino (Palmerino 2000). This last work presents an insightful examination of the reasons behind the evolution of the attitude of Father Mersenne in the lively European discussions on the Galilean science de motu. 1 I am using the version included in the edition of 1658. In this edition the title of the work was changed and a third episrulu "ad venerandum senem Iosephum Galterium" was added. The third epzstulu contains a reply of the Canon of Digne to accusations moved to him by Morin (n.

Facial hemangioma is usually isolated but its association with craniocervical arterial anomalies and structural brain malformations is well known. The acronym PHACE syndrome (posterior fossa malformation, facial hemangiomas, arterial anomalies, cardiac/aortic anomalies, and eye abnormalities) has been used to indicate that disorder in which brain anomalies are mainly represented by the Dandy-Walker malformation. We report on a 10-month-old boy affected by facial hemangioma and a complex cortical dysplasia located in the left frontal region. The lesion was characterized by a deeply infolding pachygyric cortex and a band of gray matter lining the wall of the lateral ventricle. The entire left cerebral hemisphere appeared hypoplastic. No anomalies of the posterior fossa structures or cardiac/aortic malformations were present. An overlapping clinical/pathological pattern was previously reported in another patient with facial hemangioma and cerebrovascular anomalies. These observations seem to indicate that the facial hemangiomas may be associated with disorders of the cortical development.

Intracranial calci®cation and microcephaly, which represent the main clinical features of the TORCH-syndrome, can also be determined by a rare autosomal recessive infection-like condition named pseudo-TORCH syndrome. This emerging entity has been registered in eight families so far. We report on ®ve patients from three unrelated Italian families affected by pseudo-TORCH syndrome. Reevaluation of literature allowed us to draw a speci®c clinical pro®le of the syndrome. Indeed, congenital microcephaly, congenital cerebral calci®cation, spasticity and seizures are the main clinical features, and have been present in almost all patients reported so far. On the contrary, ®ndings resembling congenital infectious diseases including neonatal icterus, hyperbilirubinemia, thrombocytopenia, and hepatomegaly, affect less than half of the patients.Considering the diagnosis of pseudo-TORCH syndrome in patients with neonatal microcephaly and cerebral calci®cation is necessary since an early diagnosis may allow adequate genetic counseling to the families.

A newly described disease is characterized by anterior bilateral temporal lobe cysts associated with multilobar leukoencephalopathy and a non-progressive clinical course. We report a patient with bilateral anterior temporal lobe cystic changes associated with a non-progressive neurological disorder, microcephaly, spasticity, mental retardation, and sensorineural deafness. From the literature, 12 other patients have shown a similar phenotype. The common neuroradiological findings in these patients have been bilateral anterior temporal lobe cystic changes and non-progressive leukoencephalopathy. By contrast, variability in the clinical phenotype has been observed, ranging from severe neuromotor handicap with mental retardation and microcephaly to spasticity in the lower limbs associated with normal cognitive function. The pathological basis of the defect remains to be defined.

PurPose. To report the case of identical dichorionic diamniotic female twins with unilateral retinoblastoma in 13q deletion syndrome. Methods. Clinical and ophthalmoscopic evaluation, combination of multiple ligation-dependent probe amplification, array-comparative genomic hybridization analyses, and magnetic resonance imaging were performed. results. Peculiar facial features, marked hypotonia, gastroesophageal reflux, interatrial septal defect with left to right shunt and light dilatation of right chambers, 5th finger hypoplasia, 3rd-5th toes clinodactyly, 2nd toe overlapped to 3rd toe, and cutis marmorata were found. Ophthalmoscopic evaluation revealed unilateral retinoblastoma in both girls. Magnetic resonance imaging detected corpus callosum hypoplasia in both twins. A 34.4-Mb deletion involving bands 13q13.2-q21.33 and including the RB1 gene was identified in both twins. The deletion was not present in the DNA of their parents and older brother. ConClusions. Dysmorphic features in children must be always suspicious of 13q deletion syndrome and a short ophthalmoscopic follow-up is necessary to detect the presence of a retinoblastoma.

Literature has suggested that changes in brain flow circulation occur in patients with multiple sclerosis. In this study, digital subtraction angiography (DSA) was used to measure the absolute CCT value in MS patients and to correlate its value to age at disease onset and duration, and to expand disability status scale (EDSS). DSA assessment was performed on eighty MS patients and on a control group of forty-four age-matched patients. CCT in MS and control groups was calculated by analyzing the angiographic images. Lesion and brain volumes were calculated in a representative group of MS patients. Statistical correlations among CCT and disease duration, age at disease onset, lesion load, brain volumes and EDSS were considered. A significant difference between CCT in MS patients (mean = 4.9s; sd = 1.27s) and control group (mean = 2.8s; sd = 0.51s) was demonstrated. No significant statistical correlation was found between CCT and the other parameters in all MS patients. Significantly increased CCT value in MS patients suggests the presence of microvascular dysfunctions, which do not depend on clinical and MRI findings. Hemodynamic changes may not be exclusively the result of a late chronic inflammatory process.

To describe the efficacy of intravitreal chemotherapy (IViC) preceded by intra-arterial chemotherapy (IAC) for the treatment of advanced stage retinoblastoma. This non-comparative interventional case series retrospectively reviewed the medical records of six patients who presented within months of each other with unilateral retinoblastoma, Reese-Ellsworth stage Vb/D of ABC classification in the affected eye. After clinical and ophthalmoscopic evaluation, they underwent MRI to exclude local and CNS dissemination. The IAC was given to treat retinal masses and intravitreal injections to treat vitreous seeding. Patients had received two cycles (six infusions) of IAC, and from six up to ten melphalan injections into the vitreous, with an interval of 7-10 days between them. From one to four intravitreal injections were performed for partial remission or consolidation. No permanent complications of procedures have been reported. All patients underwent to bimonthly MRI examination, during t...

We report here the case of a young male who started to show verbal fluency disturbance, clumsiness and gait anomalies at the age of 3.5 years and presented bilateral striatal necrosis. Clinically, the diagnosis was compatible with Leigh syndrome but the underlying molecular defect remained elusive even after exome analysis using autosomal/X-linked recessive or de novo models. Dosage of respiratory chain activity on fibroblasts, but not in muscle, underlined a deficit in complex I. Re-analysis of heterozygous probably pathogenic variants, inherited from one healthy parent, identified the p.Ala178Pro in NDUFAF6, a complex I assembly factor. RNA analysis showed an almost mono-allelic expression of the mutated allele in blood and fibroblasts and puromycin treatment on cultured fibroblasts did not lead to the rescue of the maternal allele expression, not supporting the involvement of nonsense-mediated RNA decay mechanism. Complementation assay underlined a recovery of complex I activity after transduction of the wild-type gene. Since the second mutation was not detected and promoter methylation analysis resulted normal, we hypothesized a non-exonic event in the maternal allele affecting a regulatory element that, in conjunction with the paternal mutation, leads to the autosomal recessive disorder and the different allele expression in various tissues. This paper confirms NDUFAF6 as a genuine morbid gene and proposes the coupling of exome sequencing with mRNA analysis as a method useful for enhancing the exome sequencing detection rate when the simple application of classical inheritance models fails.

Cerebrotendinous xanthomatosis (CTX) is a metabolic disease characterized by systemic signs and neurological impairment, which can be prevented if chenodeoxycholic acid (CDCA) treatment is started early. Despite brain MRI represents an essential diagnostic tool, the spectrum of findings is worth to be reappraised, and follow-up data are needed. We performed clinical evaluation and brain MRI in 38 CTX patients. Sixteen of them who were untreated at baseline examination underwent clinical and MRI follow-up after long-term treatment with CDCA. Brain MRI abnormalities included cortical and cerebellar atrophy, and T2W/FLAIR hyperintensity involving subcortical, periventricular, and cerebellar white matter, the brainstem and the dentate nuclei. Regarding the dentate nuclei, we also observed T1W/FLAIR hypointensity consistent with cerebellar vacuolation and T1W/FLAIR/SW hypointense alterations compatibly with calcification in a subgroup of patients. Long-term follow-up showed that clinical...

Peter Coebergh departs Brill as CEO Brill, the international academic publisher, announces today that Peter Coebergh will leave Brill as CEO when his term of office will come to an end after the annual general meeting of shareholders that is currently scheduled for 25 May, 2022.