828 research outputs found
The interbank market after August 2007: what has changed, and why?
The outbreak of the financial crisis coincided with a sharp increase of worldwide interbank interest rates. We analyze the micro and macroeconomic determinants of this phenomenon, finding that before August 2007 interbank rates were insensitive to borrower characteristics, whereas afterwards they became reactive to borrowers’ creditworthiness. At the same time, conditions for large borrowers became relatively more favorable, both before and after the failure of Lehman Brothers. This suggests that banks have become more discerning in their lending, a welcome change, but that moral hazard considerations related to the â€too big to fail†argument should remain a main concern for central banks.Interbank markets, Spreads, Financial crisis
The lack of the Celf2a splicing factor converts a Duchenne genotype into a Becker phenotype
Substitutions, deletions and duplications in the dystrophin gene lead to either the severe Duchenne muscular dystrophy (DMD) or mild Becker muscular dystrophy depending on whether out-of-frame or in-frame transcripts are produced. We identified a DMD case (GSΔ44) where the correlation between genotype and phenotype is not respected, even if carrying a typical Duchenne mutation (exon 44 deletion) a Becker-like phenotype was observed. Here we report that in this patient, partial restoration of an in-frame transcript occurs by natural skipping of exon 45 and that this is due to the lack of Celf2a, a splicing factor that interacts with exon 45 in the dystrophin pre-mRNA. Several experiments are presented that demonstrate the central role of Celf2a in controlling exon 45 splicing; our data point to this factor as a potential target for the improvement of those DMD therapeutic treatments, which requires exon 45 skipping
Genetic modifiers of Duchenne muscular dystrophy and dilated cardiomyopathy
OBJECTIVE:
Dilated cardiomyopathy (DCM) is a major complication and leading cause of death in Duchenne muscular dystrophy (DMD). DCM onset is variable, suggesting modifier effects of genetic or environmental factors. We aimed to determine if polymorphisms previously associated with age at loss of independent ambulation (LoA) in DMD (rs28357094 in the SPP1 promoter, rs10880 and the VTTT/IAAM haplotype in LTBP4) also modify DCM onset.
METHODS:
A multicentric cohort of 178 DMD patients was genotyped by TaqMan assays. We performed a time-to-event analysis of DCM onset, with age as time variable, and finding of left ventricular ejection fraction 70 mL/m2 as event (confirmed by a previous normal exam < 12 months prior); DCM-free patients were censored at the age of last echocardiographic follow-up.
RESULTS:
Patients were followed up to an average age of 15.9 \ub1 6.7 years. Seventy-one/178 patients developed DCM, and median age at onset was 20.0 years. Glucocorticoid corticosteroid treatment (n = 88 untreated; n = 75 treated; n = 15 unknown) did not have a significant independent effect on DCM onset. Cardiological medications were not administered before DCM onset in this population. We observed trends towards a protective effect of the dominant G allele at SPP1 rs28357094 and recessive T allele at LTBP4 rs10880, which was statistically significant in steroid-treated patients for LTBP4 rs10880 (< 50% T/T patients developing DCM during follow-up [n = 13]; median DCM onset 17.6 years for C/C-C/T, log-rank p = 0.027).
CONCLUSIONS:
We report a putative protective effect of DMD genetic modifiers on the development of cardiac complications, that might aid in risk stratification if confirmed in independent cohorts
Understanding Student Development Of Science Literacy Skills in an Undergraduate Environmental Science Course
Educators are expected to instill a variety of skills in their students that are necessary to be competent citizens of society. One such set of skills, science literacy skills, broadly encompass the ability of an individual to evaluate reliability of data and information and critically analyze and interpret them (Gormally Brickman, Hallar, & Armstrong, 2009). These skills are utilized in everyday decision-making and given their pertinence, there is a need for citizens to be scientifically literate. Thus, educators need tools and assessments to help students develop these skills and analyze their science literacy. The aim of this study was to develop science literacy interventions that could be easily incorporated into college curricula, providing instructors with exemplars of classroom interventions with the intent to improve students’ science literacy skills. Therefore, the broad research question for this investigation was: How do science literacy interventions impact student proficiency in science literacy skills in college general education courses? I measured effectiveness of the interventions using the Test of Science Literacy Skills (TOSLS, Gormally Brickman, & Lutz, 2012) pre- and post-survey scores, as well as student feedback from pre- and post-survey, follow-up interviews. The TOSLS surveys were given as part of a participation grade to students in a general education undergraduate college course (n = 148). A subset of students volunteered to be interviewed regarding specific questions from the TOSLS survey, after both the pre-survey (n = 12) and the post-survey (n = 5), to further investigate student understanding and interpretation. Interventions were designed by modifying previous assignments from earlier years’ offerings of the class and were conducted both during class and outside of class as homework extensions. These interventions were created by evaluating scores and interviews on the TOSLS survey deployed as a pilot study in a previous semester of the undergraduate course. Based on these pilot data, four survey questions encompassing different science literacy skills of particular difficulty were targeted for intervention. The interventions were: (1) An interactive clicker-based lesson involving graph selection methods; (2) Data summits involving graph interpretation and source evaluation; and (3) A role-play after which students discussed sources of bias.
Although the results indicated no statistically significant changes in the average scores between the pre-survey and post-survey (t test, p = 0.82, α = 0.05), interviewed students recalled participating in the interventions and found them useful. Pre-survey scores ranged from 18%-96% correct with a mean score of 59%. Post-surveys had a slightly smaller range of 21%-96% with a mean of 60% correct. Based on these results, more work is necessary to provide instructors with course interventions that incorporate science literacy activities that target specific components of science literacy skills. Assessments, like TOSLS, are tools that can measure science literacy skills broadly across various science courses and provide a good overview of student science literacy. By broadening the use of a single tool, measurements can be compared between classrooms to produce interventions that do not have to heavily impact curriculum pacing, yet will provide students with the tools and skills necessary to be more scientifically literate citizens
Screening for Aphasia in NeuroDegeneration for the Diagnosis of Patients with Primary Progressive Aphasia: Clinical Validity and Psychometric Properties.
BACKGROUND: We evaluated the psychometric proprieties of the Screening for Aphasia in NeuroDegeneration (SAND) battery in Italian primary progressive aphasia (PPA) and movement disorder (MD) patients. METHODS: The sample included 30 consecutive PPA and 45 MD patients who completed the SAND battery together with a clinical interview and a neurological/neuropsychological examination and 130 healthy controls (HC). RESULTS: The SAND battery showed good internal consistency and good convergent and divergent validity. receiver operating characteristic analysis revealed an area under the curve of 0.978 for PPA versus HC and of 0.786 for PPA versus MD. A cutoff ≥3 gave a sensitivity of 0.933% and a specificity of 0.946% for discriminating PPA versus HC, whereas a cutoff ≥5 gave a sensitivity of 0.767% and a specificity of 0.667% for discriminating PPA versus MD. CONCLUSION: These results indicate that the SAND battery is an adequate, reliable, and valid diagnostic tool for PPA
Unraveling biomarkers in Parkinson’s disease: the role of Insulin-like growth factor-1 (IGF-1) and DAT imaging
2015 - 2016Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's
disease, affecting up to 10 million individuals worldwide. Although symptomatic treatment
ameliorates motor symptoms, currently there are no disease-modifying treatments.
A biomarker is defined by the National Institutes of Health as “a characteristic that is objectively
measured and evaluated as an indicator of normal biological processes, pathogenic processes or
pharmacological responses to a therapeutic intervention”. Thus, biomarkers include clinical
data, measurements of biological samples (e.g., plasma, serum, cerebrospinal fluid) and application
of brain imaging techniques to detect changes in brain structure and function.
As for PD, biomarkers represent tools potentially suitable for either clinical or research settings and
useful in predicting onset, confirming diagnosis, detecting progression and evaluating the response
to disease-modifying treatments. In addition, biomarkers’ trends in different stages of disease may
reflect the widespread neurochemical and neuroanatomical changes that occur throughout the
course of PD and, thus, possibly suggest new insights in the pathophysiological mechanisms
underlying disease progression. The range of available biomarkers in PD is fast
expanding and includes an increasing number of laboratory, clinical and imaging data. ... [edited by Author]XXIX cicl
Biomarkers of Parkinson's disease: recent insights, current challenges, and future prospects
Marina Picillo,1 Marcello Moccia,2 Emanuele Spina,2 Paolo Barone,1 Maria Teresa Pellecchia1 1Department of Medicine and Surgery, Center for Neurodegenerative Diseases (CEMAND), Neuroscience Section, University of Salerno, Salerno, Italy; 2Department of Neuroscience, Reproductive and Odontostomatologic Sciences, Federico II University, Naples, Italy Abstract: A biomarker represents a tool possibly helping physicians in predicting onset, diagnosis, and progression of a disease as well as evaluating the response to disease-modifying treatments. Currently, there is no biomarker fulfilling all such ideal criteria for Parkinson's disease (PD). In this article, we have critically reviewed the literature searching for the most reliable and reproducible clinical, biochemical, and imaging biomarkers for prodromal phase, diagnosis, and progression of PD. Different comprehensive batteries of biomarkers have been proposed as a sensitive approach to predict the onset of PD during the prodromal phase. There is a discussion about the redefinition of the clinical diagnosis of PD, including clinical biomarkers as non-motor symptoms; however, on the other hand, we have also observed that imaging biomarkers support the differential diagnosis from other causes of parkinsonism. Various clinical (eg, freezing of gait or cognitive impairment), biochemical (eg, epidermal growth factor, insulin-like growth factor 1, uric acid, etc), and imaging (eg, functional magnetic resonance imaging, voxel-based morphometry, etc) biomarkers may help envisaging disease progression of PD. To conclude, given the lack of a single biomarker that could track the entire course of the disease, our challenge is to find the best combinations of biomarkers for the different stages of the disease. Keywords: biomarkers, Parkinson's disease, progression, motor, imaging , staging, non moto
Urine Sampling for Real-Time Polymerase Chain Reaction-Based Diagnosis of Canine Leishmaniasis
A real-time polymerase chain reaction (PCR) assay was used for quantifying Leishmania infantum DNA in urine samples from naturally infected dogs. Forty-one infected dogs were divided into 3 groups: 22 dogs showing only cutaneous signs (group 1), 12 dogs showing hematuria (group 2), and 7 dogs affected by severe nephropathy (group 3). Groups 2 and 3 dogs showed altered laboratory parameters related to an impairment of renal function. The real-time PCR analysis showed higher levels of Leishmania DNA in the lymph node aspirates from all groups of infected dogs versus those measured in their blood or urine. Interestingly, urine samples from dogs belonging to groups 2 and 3 contained a higher Leishmania DNA load than that detected in their blood. This finding suggests that a real-time PCR analysis of urine from infected dogs could be a useful and noninvasive tool for monitoring the severity of leishmaniasis. </jats:p
Bi-Allelic DES Gene Variants Causing Autosomal Recessive Myofibrillar Myopathies Affecting Both Skeletal Muscles and Cardiac Function
Mutations in the human desmin gene (DES) may cause both autosomal dominant and recessive cardiomyopathies leading to heart failure, arrhythmias and atrio-ventricular blocks, or progressive myopathies. Cardiac conduction disorders, arrhythmias and cardiomyopathies usually associated with progressive myopathy are the main manifestations of autosomal dominant desminopathies, due to mono-allelic pathogenic variants. The recessive forms, due to bi-allelic variants, are very rare and exhibit variable phenotypes in which premature sudden cardiac death could also occur in the first or second decade of life. We describe a further case of autosomal recessive desminopathy in an Italian boy born of consanguineous parents, who developed progressive myopathy at age 12, and dilated cardiomyopathy four years later and died of intractable heart failure at age 17. Next Generation Sequencing (NGS) analysis identified the homozygous loss-of-function variant c.634C>T; p.Arg212*, which was likely inherited from both parents. Furthermore, we performed a comparison of clinical and genetic results observed in our patient with those of cases so far reported in the literature
Development of the Digital Inclusion Questionnaire (DIQUEST) in Parkinson's Disease
Background No tool is currently able to measure digital inclusion in clinical populations suitable for telemedicine. We developed the "Digital Inclusion Questionnaire" (DIQUEST) to estimate access and skills in Parkinson's Disease (PD) patients and verified its properties with a pilot study.Methods Thirty PD patients completed the initial version of the DIQUEST along with the Mobile Device Proficiency Questionnaire (MDPQ) and a practical computer task. A Principal Components Analysis (PCA) was conducted to define the DIQUEST factor structure and remove less informative items. We used Cronbach's alpha to measure internal reliability and Spearman's correlation test to determine the convergent and predictive validity with the MDPQ and the practical task, respectively.Results The final version of the DIQUEST consisted of 20 items clustering in five components: "advanced skills," "navigation skills," "basic skills/knowledge," "physical access," and "economical access." All components showed high reliability (alpha > 0.75) as did the entire questionnaire (alpha = 0.94). Correlation analysis demonstrated high convergent (rho: 0.911; p<0.001) and predictive (rho: 0.807; p<0.001) validity.Conclusions We have here presented the development of the DIQUEST as a screening tool to assess the level of digital inclusion, particularly addressing the access and skills domains. Future studies are needed for its validation beyond PD
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