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This paper takes advantage of the COVID-19 outbreak to explore the determinants of firms' R&D choices around an exogenous shock. We make use of unique panel data on 7,800 Italian companies between January –right before the pandemic– and March 2020 –amid lockdown policies. We exploit the short-run revision in firms' research plans to test the impact of deteriorating expectations and uncertainty on firms' R&D. In addition to the significant role played by firms' expectations, we find that preexisting innovative activities significantly shaped the reaction to the general uncertainty shock. • We explore the determinants of firms R&D choices around an exogenous shock. • We test the differential effect of deteriorating expectations and uncertainty on firms' R&D. • Expectations on future demand have a dramatic effect, especially for innovative companies. • Characteristics of the innovative process shape firms' reaction to the general uncertainty. • Newly innovative and transitioning companies are particularly affected. [ABSTRACT FROM AUTHOR]

We study the financial and real effects of political risk shocks for Italy, Spain, Ireland, Portugal and Greece between 2008 and 2019. We build an instrument for these shocks using the changes of the sovereign yield spread around political and policy dates, and estimate their effects in the context of local projection. We show that adverse political risk shocks have negative effects on domestic financial markets and in some countries generate spillovers on the spreads of other eurozone economies. Moreover, in Italy populism-related political risk shocks have a larger effect on financial markets and they harm the real economy. [ABSTRACT FROM AUTHOR]

Gilteritinib has been approved as monotherapy in adults with acute myeloid leukemia (AML) FLT3 mutated with relapsed or refractory disease, in light of its advantages in terms of survival and the favorable safety profile. Hepatobiliary disorders and musculoskeletal and connective tissue disorders represent the most frequent adverse reactions associated with gilteritinib, whereas the most frequent serious adverse reaction is acute kidney injury. In the summary of product characteristics, gastrointestinal (GI) events are indicated as very common, in particular diarrhea, nausea and stypsis. Furthermore, serious GI disorders have been observed with gilteritinib in clinical trials, including GI hemorrhage, GI perforation and GI obstruction. However, the association with the FLT3 inhibitor has not been confirmed. Nevertheless, serious GI AEs have been recognized as an important potential risk to be monitored in postmarketing surveillance. We present three cases of serious self-limiting GI events observed in patients on gilteritinib treatment for AML, and an analysis of relevant available postmarketing surveillance data. [ABSTRACT FROM AUTHOR]

Are there any factors driving firms' internationalization process other than productivity? By means of a firm-level data set on manufacturing and production services sectors collected by MET, this article investigates the export performance of enterprises in Italy in the aftermath of the recent economic crisis. Our results suggest that productivity is not the only (and most important) determinant in this matter. Innovation activity and learning processes are indeed pivotal in boosting enterprises to sell their products abroad and, to a certain extent, in backing their success on foreign markets. In particular, by estimating dynamic probability models, as well as Tobit II-Heckman and two-part models, we provide evidence that firm's ability to learn from its past export experiences lowers international trade informal barriers, while its ability to learn, thanks to local spillovers, is important in terms of both extensive and intensive performances on foreign markets. [ABSTRACT FROM AUTHOR]

We identify as political transformists the Italian members of parliament (MPs) who cross the aisle and vote for legislation opposed by their own political group—i.e., MPs who transform from the political opposition to the ruling parties (or from government supporters) into a force supporting the government (or opposition)—thus representing sources of party and governmental instability. Transformism, which characterized 471 MPs over the period considered, does not coincide with the broader phenomena of party switching already studied in political science. Once we disentangle the distinct behaviors, we study whether transformism helps extend the tenures of all 7128 MPs observed from 1946 to 2013. To the best of our knowledge, ours is the first work to consider the role of transformism in the survival of politicians. Our results suggest that transforming MPs suffer marked reductions in their survival probabilities, especially when compared with their fellow parliamentarians. However, transformist MPs, immediately after coming out as such, are more likely to survive than MPs remaining reliably loyal to their parties. That is, over time, transformists are punished by the electorate, but newly transformed politicians enjoy short-term comparative electoral advantages, thus shedding light on the relevance of a long-standing Italian political phenomenon. [ABSTRACT FROM AUTHOR]

Fertility preservation represents one important goal of cancer patients' management due to the high impact on health and quality of life of survivors. The available preventive measures cannot be performed in all patients and are not feasible in all health-care facilities. Therefore, the pharmacological treatment with GnRHa has become a valuable non-invasive and well-tolerated alternative, especially in those who cannot access to cryopreservation options due to clinical and/or logistic issues. Supporting data demonstrate a significant advantage for the survivors who received GnRHa in the long-term maintenance of ovarian function and preservation of fertility. The prevention of the risk of ovarian failure with GnRHa is a typical off-label use, defined as the administration of a medicinal product not in accordance with the authorized product information. Italy has officially recognized the off-label use of GnRHa in adult women at risk of premature and permanent menopause following chemotherapy. However, fertility preservation still represents an unmet medical need in adolescents who cannot access to other treatment options. [ABSTRACT FROM AUTHOR]

We studied the clinical, neuropsychological, neurophysiologic, and genetic features of an Italian family with familial cortical myoclonic tremor with epilepsy (FCMTE). Clinically affected members of the family had limb and voice tremor, seizures, and myoclonus involving the eyelids during blinking. Neuropsychological testing disclosed visuospatial impairment, possibly due to temporal lobe dysfunction. Neurophysiologic findings suggested increased primary motor cortex excitability with normal sensorimotor integration. Linkage analysis excluded the 8q24 locus, where patients shared a common haplotype spanning 14.5 Mb in the pericentromeric region of chromosome 2. [ABSTRACT FROM AUTHOR]

Cohen syndrome is an autosomal recessive disorder with variability in the clinical manifestations, characterized by developmental delay, visual disability, facial dysmorphisms and intermittent neutropenia. We described a cohort of 10 patients affected by Cohen syndrome from nine Italian families ranging from 5 to 52 years at assessment. Characteristic age related facial changes were well documented. Visual anomalies, namely retinopathy and myopia, were present in 9/10 patients (retinopathy in 9/10 and myopia in 8/10). Truncal obesity has been described in all patients older than 6 years (8/8). DNA samples from all patients were analyzed for mutations in COH1 by DHPLC. We detected 15 COH1 alterations most of them were truncating mutations, only one being a missense change. Partial gene deletions have been found in two families. Most mutations were private. Two were already reported in the literature just once. A single base deletion leading to p.T3708fs3769, never reported before, was found in three apparently unrelated families deriving from a restricted area of the Veneto’s lowland, between Padova town and Tagliamento river, in heterozygous state. Given the geographical conformation of this region, which is neither geographically or culturally isolated, a recent origin of the mutation could be hypothesized. [ABSTRACT FROM AUTHOR]

Background and aims: To survey all Residential Facilities (RFs) for older people (more than 50% residents over 65 years of age) in five Italian regions (Calabria, Sardinia, Sicily, Umbria, Veneto), and to evaluate their logistic and organizational characteristics and staff and resident features. Methods: Structured interviews with RF managers; selected RFs operating in five regions. Results: A total of 853 RFs were operating in the five regions, with an average of 198.0 beds per 10,000 older people -- a rate showing marked regional variability. The number of RFs actually surveyed was 754 (88.4% of sample pool). The mean number of RF beds was 59.8 (±65.0; median: 34), and the great majority (96%) had 24-hour staff cover. A large proportion (29%) were managed by local municipal authorities, religious non-profit associations (approx. 24%) and other non-profit organizations (approx. 21%). In the RFs 24,456 workers were employed; the number of staff per facility also showed great variability. The mean number of workers directly involved in resident care was 27.8 (±39.0; range: 1-331); the median number of staff members was 14, and the resident/staff ratio was 2.1. These 754 RFs hosted 42,687 residents, with an average of 53.5 (±58.5) older people in each facility, and 3.2 residents below the age of 65. The mean age of the entire resident sample was 79.3 years (±5.2) and there was a high proportion of residents with neurological (including dementia), psychiatric and medical disorders. Conclusions: The five regions varied considerably in residential bed provision; many other RF characteristics, including staff/resident ratios, showed similar variability. Most RFs hosted older people with a variety of neurological, psychiatric and medical disorders. Future phases of the project will aim at shedding light on many other features in these institutions, which care for 2.1% of the older population in Italy and may serve even greater proportions of older people in the future. [ABSTRACT FROM AUTHOR]

• Electroconvulsive therapy is available to a handful of public facilities in Italy. • Most patients are not referred for ECT before multiple medications have been tried. • Drug exposure is not associated with reduced response to ECT in bipolar depression. • Remission rate after ECT is significantly reduced in case of multiple drug failures. Episode chronicity and medication failure are considered robust predictors of poor response to electroconvulsive therapy (ECT). In this study we explored the associations between indexes of drug exposure during current episode and outcomes of ECT in 168 bipolar depressive patients. The association between response or remission and number of previous pharmacological trials, failure of treatment with antidepressants, antipsychotics or combinations, and sum of maximum Antidepressant Treatment History Form (ATHF) scores obtained in each pharmacological class were tested. 98 patients (58%) were considered responders and 21 remitters (13%). Number of trials, number of adequate trials, ATHF sum, antidepressant-antipsychotic combination therapy failure and failure of two adequate trials were significantly negatively associated with remission. The association with ATHF sum stayed significant when controlling for episode duration and manic symptoms and survived stepwise model selection. No significant associations with response were identified. In conclusion, a history of multiple drug treatments may be linked to a greater resistance to all types of therapies, including ECT. However, we could not exclude that, at least in some patients, a prolonged exposure to pharmacological treatments may be responsible for a greater chronicity and for the presence of residual symptoms, which would explain reduced remission after ECT. [ABSTRACT FROM AUTHOR]

Background: For a number of persons with rare diseases (RDs) a definite diagnosis remains undiscovered with relevant physical, psychological and social consequences. Undiagnosed RDs (URDs) require other than specialised clinical centres, outstanding molecular investigations, common protocols and dedicated actions at national and international levels; thus, many "Undiagnosed RDs programs" have been gradually developed on the grounds of a well-structured multidisciplinary approach. Methods: The Italian Undiagnosed Rare Diseases Network (IURDN) was established in 2016 to improve the level of diagnosis of persons with URD living in Italy. Six Italian Centres of Expertise represented the network. The National Centre for Rare Diseases at the Istituto Superiore di Sanità coordinates the whole project. The software PhenoTips was used to collect the information of the clinical cases. Results: One hundred and ten cases were analysed between March 2016 and June 2019. The age of onset of the diseases ranged from prenatal age to 51 years. Conditions were predominantly sporadic; almost all patients had multiple organs involvements. A total of 13/71 family cases were characterized by WES; in some families more than one individual was affected, so leading to 20/71 individuals investigated. Disease causing variants were identified in two cases and were associated to previously undescribed phenotypes. In 5 cases, new candidate genes were identified, although confirmatory tests are pending. In three families, investigations were not completed due to the scarce compliance of members and molecular investigations were temporary suspended. Finally, three cases (one familial) remain still unsolved. Twelve undiagnosed clinical cases were then selected to be shared at International level through PhenomeCentral in accordance to the UDNI statement. Conclusions: Our results showed a molecular diagnostic yield of 53,8%; this value is comparable to the diagnostic rates reported in other international studies. Cases collected were also pooled with those collected by UDNI International Network. This represents a unique example of global initiative aimed at sharing and validating knowledge and experience in this field. IURDN is a multidisciplinary and useful initiative linking National and International efforts aimed at making timely and appropriate diagnoses in RD patients who still do not have a confirmed diagnosis even after a long time. [ABSTRACT FROM AUTHOR]

Niemann-Pick type C (NPC) disease is an autosomal recessive lysosomal storage disorder caused by mutations in NPC1 or NPC2 genes. In 2009, the molecular characterization of 44 NPC Italian patients has been published. Here, we present an update of the genetic findings in 105 Italian NPC patients belonging to 83 unrelated families (77 NPC1 and 6 NPC2). NPC1 and NPC2 genes were studied following an algorithm recently published. Eighty-four different NPC1 and five NPC2 alleles were identified. Only two NPC1 alleles remained non detected. Sixty-two percent of NPC1 alleles were due to missense variants. The most frequent NPC1 mutation was the p.F284Lfs*26 (5.8% of the alleles). All NPC2 mutations were found in the homozygous state, and all but one was severe. Among newly diagnosed patients, 18 novel NPC1 mutations were identified. The pathogenic nature of 7/9 missense alleles and 3/4 intronic variants was confirmed by filipin staining and NPC1 protein analysis or mRNA expression in patient's fibroblasts. Taken together, our previous published data and new results provide an overall picture of the molecular characteristics of NPC patients diagnosed so far in Italy. [ABSTRACT FROM AUTHOR]

Several studies have demonstrated that bone has the power of regeneration and repair. BMPs (bone morphogenetic proteins) are involved in the determination of osteoblast phenotype and bone turnover, therefore genes coding for these proteins, like BMP-4, could be considered potential candidate genes for osteoporosis. We investigated the association of BMP-4 gene polymorphism with osteoporosis in a cohort of 72 osteoporotic, postmenopausal women and 82 unrelated controls. We failed to detect any significant association between this genetic marker and the disease. [ABSTRACT FROM AUTHOR]

Describes an Italian kindred with nine individuals affected by hyperkalemic periodic paralysis associated with paramyotonia congenita. Severe periodic paralysis with several episodes a day lasting for hours; Observation that the paralytic episodes were refractory to treatment; Minimal paramyotonia, mainly of the eyelids and hands; Finding that all affected family members carried the threonine to methionine substitution at codon 704 in exon 13 of the skeletal muscle voltage gated sodium channel gene.

• Mutational screening of the FBN1 gene for the diagnosis of Marfan Syndrome (MFS). • Detection rate for FBN1 variants in the study group is 86.3% (107/124 patients). • FBN1 screening facilitates MFS diagnosis specially in young presymptomatic patients. • Multidisciplinary clinical evaluation improves MFS management and outcomes. Marfan Syndrome (MFS) is a chronic, life-threatening, autosomal dominant connective tissue disorder caused by mutations in the FBN1 gene, coding for fibrillin-1. All organ systems may be affected, but particularly the cardiovascular system, eyes, and skeleton. Mortality generally results from cardiovascular complications, mainly aortic dissection. Currently, the diagnosis of MFS is based on the revised Ghent nosology. Molecular analysis of the FBN1 gene reduces diagnostic uncertainty in patients with suspected MFS or MFS-related disorders (MFS-RD). To date, more than 2700 FBN1 mutations are known. Using Next Generation Sequencing (NGS) followed by Multiplex Ligation-dependent Probe Amplification on NGS-negative samples, we screened FBN1 gene on 124 unrelated patients (101 MFS fulfilling revised Ghent criteria, 20 suspected MFS, 3 MFS-RD) enrolled from 2008 to 2018 at the Multidisciplinary Marfan Clinic, Tor Vergata Hospital, Rome. An FBN1 variant was identified in 107/124 (86.3%) patients, including 48 novel variants (46 pathogenic/likely pathogenic, 2 VUS). A pathogenic/likely pathogenic variant was detected in 90/101 (89.1%) MFS patients. Our approach allowed early diagnosis for 10 young patients (age 3–19 years) with suspected MFS. This study broadens the mutation spectrum of FBN1, providing a full update of the molecular basis of MFS in Italy. [ABSTRACT FROM AUTHOR]

Abstract: Forty years ago in a xxth-century church in Torino, a small fire partially burned some of the decorative external boards of the sound-box of the organ. The focus of this present work was to find a treatment able to consolidate partially burnt wood in dry conditions, in which the external charred layer would be lost if not well preserved because of its incoherence. The product had to be applied onsite on an architectural structure intended to be reused again (and not simply exhibited). This circumstance is rarely encountered in the conservation of wooden Cultural Heritage. The efficacy of treatments was evaluated on the basis of a suitable and original experimental methodology, which took into account both the immediate and long-term behaviour of the various tested products. Although the opportunity to carry out this work came from a real case, both the selected product and the set up evaluation methodology have a general validity and they can be effectively used in other similar situations in which a slight antipowdering effect is required for treatment. [Copyright &y& Elsevier]

Objectives: Baseline characteristics of the population enrolled in the ISSO study, designed to evaluate the incidence of vertebral and non-vertebral fractures in Italian patients with severe osteoporosis treated according to clinical practice over 24 months observation., Methods: Prospective observational study in 783 post-menopausal women and men entering 18-month treatment with teriparatide in a community setting at 57 centres in Italy. Characterisation included demographics, fracture risk factors, bone mineral density, fracture status, Health-Related Quality of Life (HRQoL) measured by the European Quality of Life Questionnaire, EQ-5D, and back pain assessed by VAS., Results: Most patients were elderly women (90.5%), mean age±SD was 72.9±8.8 years. Nearly all (91.3%) had experienced ≥ 1 vertebral fracture (mean±SD, 3.6±2.2 per patient), 37.5% had ≥ 1 non-vertebral fracture (mean±SD, 1.4±0.7 per patient). Nearly all patients were suffering from back pain (94.9%), which had significantly restricted their daily activities (51.7%) and had likely or very likely been caused by vertebral fractures (29.2% and 55.8%, respectively). Mean EuroQoL EQ-5D index value was 0.58±0.25 and VAS score 49.2±23.6. Non-vertebral fractures, back pain and multiple vertebral fractures were associated with lower HRQoL (EuroQoL-5D Index both p<0.001, EQ-5D VAS score p=0.025 and p<0.016, respectively). Many patients were physically inactive (81.1%). One third (34.7%) of population had co-morbidities and 60.5% were on chronic concomitant treatments. Few subjects reported a maternal history of osteoporosis (15.5%), regular consumption of alcohol (13.3%) or were current smokers (11.5%). Nearly two-thirds (71.5%) had already been treated for osteoporosis, mainly with bisphosphonates. Calcium and vitamin D supplements were taken by 13% and 15.5% of the total population, respectively., Conclusions: At enrollment, the population of ISSO study mostly consisted in aging women, who had osteoporosis with high fracture risk, poor HRQoL and suffered from significant back pain. Most of them had already been treated by bisphosphonates but without calcium and vitamin D supplements. Back pain, as well as non-vertebral and multiple vertebral fractures, were associated with lower HRQoL.