Radio recombination lines from obscured quasars with the SKA

We explore the possibility of detecting hydrogen radio recombination lines from 0 < z < 10 quasars. We compute the expected Hnalpha flux densities as a function of absolute magnitude and redshift by considering (i) the range of observed AGN spectral indices from UV to X-ray bands, (ii) secondary ionizations from X-ray photons, and (iii) stimulated emission due to nonthermal radiation. All these effects are important to determine the line fluxes. We find that the combination of slopes: alpha_X,hard = -1.11, alpha_X,soft = -0.7, alpha_EUV = -1.3, alpha_UV = -1.7, maximizes the expected flux, f_Hnalpha = 10 microJy for z = 7 quasars with M_AB = -27 in the n = 50 lines; allowed SED variations produce variations by a factor of 3 around this value. Secondaries boost the line intensity by a factor of 2 to 4, while stimulated emission in high-z quasars with M_AB = -26 provides an extra boost to RRL flux observed at nu = 1 GHz if recombinations arise in HII regions with T_e = 10^3-5 K, n_e = 10^3-5 cm^-3. We compute the sensitivity required for a 5sigma detection of Hnalpha lines using the SKA, finding that the SKA-MID could detect sources with M_AB < -27 (M_AB < -26) at z < 8 (z < 3) in less than 100 hrs of observing time. These observations could open new paths to searches for obscured SMBH progenitors, complementing X-ray, optical/IR and sub-mm surveys.Comment: 11 pages, 9 figures; to be published in Monthly Notices of the Royal Astronomical Society Main Journa

Classical and quantum Big Brake cosmology for scalar field and tachyonic models

We study a relation between the cosmological singularities in classical and quantum theory, comparing the classical and quantum dynamics in some models possessing the Big Brake singularity - the model based on a scalar field and two models based on a tachyon-pseudo-tachyon field . It is shown that the effect of quantum avoidance is absent for the soft singularities of the Big Brake type while it is present for the Big Bang and Big Crunch singularities. Thus, there is some kind of a classical - quantum correspondence, because soft singularities are traversable in classical cosmology, while the strong Big Bang and Big Crunch singularities are not traversable.Comment: final version, to appear in Phys. Rev.

The recurrent pathogenic Pro890Leu substitution in CLTC causes a generalized defect in synaptic transmission in Caenorhabditis elegans

De novo CLTC mutations underlie a spectrum of early-onset neurodevelopmental phenotypes having developmental delay/intellectual disability (ID), epilepsy, and movement disorders (MD) as major clinical features. CLTC encodes the widely expressed heavy polypeptide of clathrin, a major component of the coated vesicles mediating endocytosis, intracellular trafficking, and synaptic vesicle recycling. The underlying pathogenic mechanism is largely unknown. Here, we assessed the functional impact of the recurrent c.2669C &gt; T (p.P890L) substitution, which is associated with a relatively mild ID/MD phenotype. Primary fibroblasts endogenously expressing the mutated protein show reduced transferrin uptake compared to fibroblast lines obtained from three unrelated healthy donors, suggesting defective clathrin-mediated endocytosis. In vitro studies also reveal a block in cell cycle transition from G0/G1 to the S phase in patient's cells compared to control cells. To demonstrate the causative role of the p.P890L substitution, the pathogenic missense change was introduced at the orthologous position of the Caenorhabditis elegans gene, chc-1 (p.P892L), via CRISPR/Cas9. The resulting homozygous gene-edited strain displays resistance to aldicarb and hypersensitivity to PTZ, indicating defective release of acetylcholine and GABA by ventral cord motor neurons. Consistently, mutant animals show synaptic vesicle depletion at the sublateral nerve cords, and slightly defective dopamine signaling, highlighting a generalized deficit in synaptic transmission. This defective release of neurotransmitters is associated with their secondary accumulation at the presynaptic membrane. Automated analysis of C. elegans locomotion indicates that chc-1 mutants move slower than their isogenic controls and display defective synaptic plasticity. Phenotypic profiling of chc-1 (+/P892L) heterozygous animals and transgenic overexpression experiments document a mild dominant-negative behavior for the mutant allele. Finally, a more severe phenotype resembling that of chc-1 null mutants is observed in animals harboring the c.3146 T &gt; C substitution (p.L1049P), homologs of the pathogenic c.3140 T &gt; C (p.L1047P) change associated with a severe epileptic phenotype. Overall, our findings provide novel insights into disease mechanisms and genotype-phenotype correlations of CLTC-related disorders

Cosmic large scale structure: insights from radio astronomical experiments

From the introduction: "In this Thesis work we focus on the fundamental role that the Square Kilometre Array (SKA) will play in the search for Radio Recombination Lines (RRLs) from quasars and in radio-continuum observations of large scale structures, as, e.g. galaxy clusters. Moreover, we investigate the relationship between quasars and their host galaxies through studies of the cosmic LSS"

Quasar UV luminosity function evolution up to z = 8

We study the redshift evolution of the quasar (QSO) UV luminosity function (LF) for 0.5 &lt; z &lt; 6.5, by collecting the most up to date observational data and, in particular, the recently discovered population of faint active galactic nuclei (AGNs). We fit the QSO LF using either a double power-law function or a Schechter function, finding that both forms provide good fits to the data. We derive empirical relations for the LF parameters as a function of redshift and, based on these results, predict the QSO UV LF at z = 8. From the inferred LF evolution, we compute the redshift evolution of the QSO/AGN comoving ionizing emissivity and hydrogen photoionization rate. If faint AGNs are included, the contribution of QSOs to reionization increases substantially. However, their level of contribution critically depends on the detailed shape of the QSO LF, which can be constrained by efficient searches of high-z QSOs. To this aim, we predict the expected (i) number of z &gt; 6 QSOs detectable by ongoing and future near-infrared surveys (as EUCLID and Wide-Field Infrared Survey Telescope), and (ii) number counts for a single radio-recombination line observation with Square Kilometre Array-MID (FoV = 0.49 deg2) as a function of the Hn\u3b1 flux density, at 0 &lt; z &lt; 8. These surveys (even at z &lt; 6) will be fundamental to better constrain the role of QSOs as reionization sources

LOSS OF CONTINUITY OF CARE IN PEDIATRIC NEUROLOGY SERVICES DURING COVID-19 LOCKDOWN: AN ADDITIONAL STRESSOR FOR PARENTS

Objective: COVID 19-related lockdown during the so called "first wave" of the current pandemics had a deep impact on the health and the care of children with chronic neurologic disease and neurodevelopmental disorders. This work aimed to investigate its consequence on the wellbeing of children with neurological and neurodevelopmental disorders and the repercussion on parental stress. Methods: A web-based survey was shared via mail with the parents of children affected by chronic neurologic disorders and neurodevelopmental disorders in continuity of care in two Italian tertiary centers(june-july 2020). Parental stress was measured via Perceived Stress Scale (PSS). Results: The survey was completed by 250 parents. Sars-Cov2 infection was reported in 2 patients only. 44,2% of the sample completely interrupted school activities while 70% of parents underwent changes in their job modalities. Health care services were disrupted in 77% of patients and higher PSS scores were detected in parents who reported a significant loss of usual clinical checks. Conclusions: The loss of continuity of care during the lockdown has to be considered as a risk factor for parents caring for children with chronic neurologic diseases and neurodevelopmental disorder in furthers phases of the current pandemics

Loss of Continuity of Care in Pediatric Neurology Services during COVID-19 Lockdown: An Additional Stressor for Parents

Background. This study aimed to investigate the consequence of the COVID 19-related lockdown on the well-being of children with neurological and neurodevelopmental disorders and the repercussion on parental stress during the period 9 March 2020–3 May 2020. Methods. A web-based survey was shared via mail with the parents of children affected by chronic neurologic disorders and neurodevelopmental disorders in the continuity of care in two Italian tertiary centers, independently by the severity of the diseases and the required frequency of controls. For each patient, they were asked to identify a single main caregiver, among the two parents, to fill in the questionnaire. Parental stress was measured via the Perceived Stress Scale (PSS). Statistical analysis was performed with IBM SPSS Statistics version 25. The differences between the clinical groups were performed with one way ANOVA. The dimensional effect of the clinical variables on outcome was evaluated by multiple linear regression analysis. Results. The survey was completed by 250 parents (response rate = 48.9 %). Sars-Cov2 infection was reported in two patients only. A total of 44.2% of the patients had completely interrupted school activities while 70% of parents underwent changes in their job modalities. Health care services were disrupted in 77% of patients. Higher PSS scores were detected in the parents of children with neurodevelopmental disorders (p = 0.035). Conclusions. The loss of continuity of care during the lockdown must be considered as a risk factor for parents caring for children with chronic neurologic diseases and neurodevelopmental disorders in further phases of the current pandemic

First report of <i>Cylindrospermopsis raciborskii</i> in Italy

Cylindrospermopsis raciborskii is a freshwater cyanobacterium of tropical origin, also found in temperate regions. It can produce toxins like cylindrospermopsin (CYN) and saxitoxins (STX, NEO). In 2004, it was detected in three Italian lakes (Albano Lake, Trasimeno Lake and Cedrino Lake). Two of the three examined cases were toxic to a liquid chromatography coupled with tandem spectrometry apparatus (LC-MS/MS), and analysis demonstrated the presence of cylindrospermopsin (CYN). Formerly C. raciborskii blooms were detected in 1995 (Trasimeno Lake), in 2002 (Albano Lake) and in 2003 (Cedrino Lake), but in those cases no toxicity analysis were performed due to the lack of a standard toxin

Neurophysiological assessment of juvenile parkinsonism due to primary monoamine neurotransmitter disorders

No studies have investigated voluntary movement abnormalities and their neurophysiological correlates in patients with parkinsonism due to inherited primary monoamine neurotransmitter (NT) disorders. Nine NT disorders patients and 16 healthy controls (HCs) were enrolled. Objective measurements of repetitive finger tapping were obtained using a motion analysis system. Primary motor cortex (M1) excitability was assessed by recording the input/output (I/O) curve of motor-evoked potentials (MEP) and using a conditioning test paradigm for short-interval intracortical inhibition (SICI) assessment. M1 plasticity-like mechanisms were indexed according to MEPs amplitude changes after the paired associative stimulation protocol. Patient values were considered abnormal if they were greater or lower than two standard deviations from the average HCs value. Patients with aromatic amino acid decarboxylase, tyrosine hydroxylase, and 6-pyruvoyl-tetrahydropterin synthase defects showed markedly reduced velocity (5/5 patients), reduced movement amplitude, and irregular rhythm (4/5 patients). Conversely, only 1 out of 3 patients with autosomal-dominant GTPCH deficiency showed abnormal movement parameters. Interestingly, none of the patients had a progressive reduction in movement amplitude or velocity during the tapping sequence (no sequence effect). Reduced SICI was the most prominent neurophysiological abnormality in patients (5/9 patients). Finally, the I/O curve slope correlated with movement velocity and rhythm in patients. We provided an objective assessment of finger tapping abnormalities in monoamine NT disorders. We also demonstrated M1 excitability changes possibly related to alterations in motor execution. Our results may contribute to a better understanding of the pathophysiology of juvenile parkinsonism due to dopamine deficiency

TRAPPC9-related autosomal recessive intellectual disability: report of a new mutation and clinical phenotype

Intellectual disability (ID) with autosomal recessive (AR) inheritance is believed to be common; however, very little is known about causative genes and genotype-phenotype correlations. The broad genetic heterogeneity of AR-ID, and its usually nonsyndromic nature make it difficult to pool multiple pedigrees with the same underlying genetic defect to achieve consistent nosology. Nearly all autosomal genes responsible for recessive cognitive disorders have been identified in large consanguineous families from the Middle East, and nonsense mutations in TRAPPC9 have been reported in a total of 5. Although several recurrent phenotypic abnormalities are described in some of these patients, the associated phenotype is usually referred to as nonsyndromic. By means of single-nucleotide polymorphism-array first and then by exome sequencing, we identified a new pathogenic mutation in TRAPPC9 in two Italian sisters born to healthy and apparently nonconsanguineous parents. It consists of a homozygous splice site mutation causing exon skipping with frameshift and premature termination, as confirmed by mRNA sequencing. By detailed phenotypic analysis of our patients, and by critical literature review, we found that homozygous TRAPPC9 loss-of-function mutations cause a distinctive phenotype, characterized by peculiar facial appearance, obesity, hypotonia (all signs resembling a Prader-Willi-like phenotype), moderate-to-severe ID, and consistent brain abnormalities.European Journal of Human Genetics advance online publication, 2 May 2012; doi:10.1038/ejhg.2012.79