Robust Small Sample Accurate Inference in Moment Condition Models

Procedures based on the Generalized Method of Moments (GMM) (Hansen, 1982) are basic tools in modern econometrics. In most cases, the theory available for making inference with these procedures is based on first order asymptotic theory. It is well-known that the (first order) asymptotic distribution does not provide accurate p-values and confidence intervals in moderate to small samples. Moreover, in the presence of small deviations from the assumed model, p-values and confidence intervals based on classical GMM procedures can be drastically affected (nonrobustness). Several alternative techniques have been proposed in the literature to improve the accuracy of GMM procedures. These alternatives address either the first order accuracy of the approximations (information and entropy econometrics (IEE)) or the nonrobustness (Robust GMM estimators and tests). In this paper, we propose a new alternative procedure which combines robustness properties and accuracy in small samples. Specifically, we combine IEE techniques as developed in Imbens, Spady, Johnson (1998) to obtain finite sample accuracy with robust methods obtained by bounding the original orthogonality function as proposed in Ronchetti and Trojani (2001). This leads to new robust estimators and tests in moment condition models with excellent finite sample accuracy. Finally, we illustrate the accuracy of the new statistic by means of some simulations for three models on overidentifying moment conditions.Exponential tilting, Generalized method of moments, Information and entropy econometrics, Monte Carlo, Robust tests, Saddlepoint techniques

Novel deletions causing pseudoxanthoma elasticum underscore the genomic instability of the ABCC6 region

Mutations in ABCC6 cause pseudoxanthoma elasticum (PXE), a heritable disease that affects elastic fibers. Thus far, >200 mutations have been characterized by various PCR-based techniques (primarily direct sequencing), identifying up to 90% of PXE-causing alleles. This study wanted to assess the importance of deletions and insertions in the ABCC6 genomic region, which is known to have a high recombinational potential. To detect ABCC6 deletions/insertions, which can be missed by direct sequencing, multiplex ligation-dependent probe amplification (MLPA) was applied in PXE patients with an incomplete genotype. MLPA was performed in 35 PXE patients with at least one unidentified mutant allele after exonic sequencing and exclusion of the recurrent exon 23-29 deletion. Six multi-exon deletions and four single-exon deletions were detected. Using MLPA in addition to sequencing, we expanded the ABCC6 mutation spectrum with 9 novel deletions and characterized 25% of unidentified disease alleles. Our results further illustrate the instability of the ABCC6 genomic region and stress the importance of screening for deletions in the molecular diagnosis of PXE. Journal of Human Genetics (2010) 55, 112-117; doi: 10.1038/jhg.2009.132; published online 15 January 201

LncRNA NEAT1 in Paraspeckles: A Structural Scaffold for Cellular DNA Damage Response Systems?

Nuclear paraspeckle assembly transcript 1 (NEAT1) is a long non-coding RNA (lncRNA) reported to be frequently deregulated in various types of cancers and neurodegenerative processes. NEAT1 is an indispensable structural component of paraspeckles (PSs), which are dynamic and membraneless nuclear bodies that affect different cellular functions, including stress response. Furthermore, increasing evidence supports the crucial role of NEAT1 and essential structural proteins of PSs (PSPs) in the regulation of the DNA damage repair (DDR) system. This review aims to provide an overview of the current knowledge on the involvement of NEAT1 and PSPs in DDR, which might strengthen the rationale underlying future NEAT1-based therapeutic options in tumor and neurodegenerative diseases

Using Virtual Reality to Rehabilitate Neglect

Purpose: Virtual Reality (VR) platforms gained a lot of attention in the rehabilitation field due to their ability to engage patients and the opportunity they offer to use real world scenarios. As neglect is characterized by an impairment in exploring space that greatly affects daily living, VR could be a powerful tool compared to classical paper and pencil tasks and computer training. Nevertheless, available platforms are costly and obstructive. Here we describe a low cost platform for neglect rehabilitation, that using consumer equipments allows the patient to train at home in an intensive fashion. Method: We tested the platform on IB, a chronic neglect patient, who did not benefit from classical rehabilitation. Results: Our results show that IB improved both in terms of neglect and attention. Importantly, these ameliorations lasted at a follow up evaluation 5 months after the last treatment session and generalized to everyday life activities. Conclusions: VR platforms built using equipment technology and following theoretical principles on brain functioning may induce greater ameliorations in visuo-spatial deficits than classical paradigms possibly thanks to the real world scenarios in association with the "visual feedback" of the patient's own body operating in the virtual environmen

Acquisizione di rumore sismico nell'Appennino Reggiano Modenese 11-15 aprile 2006

Tra l’11 e il 15 aprile 2006 è stata condotta una campagna di acquisizione di rumore sismico in alcuni siti in frana dell’Appennino Settentrionale. Lo scopo dell’esperimento è quello di stimare gli effetti di sito su corpi franosi tipici dell’Appennino Modenese e Reggiano, nonché di studiare il comportamento delle frane quando sono soggette ad eventi sismici. Le registrazioni di rumore sono state effettuate con stazioni equipaggiate con sensori a corto periodo a tre componenti. Per la stima dell’amplificazione locale è stata scelta una serie di siti caratterizzati da litologie diverse. Inoltre, in siti omogenei e ben studiati dal punto di vista strutturale, sono state effettuate delle misure di rumore in configurazione di array per la stima di un modello di velocità superficiale, allo scopo di confrontare i risultati sperimentali con le funzioni di trasferimento teoriche. La durata delle registrazione non è stata inferiore ad un’ora per ogni sito. Le misure sono state effettuate sulle frane di Ca’ Lita (MO), Cavola (RE) e La Lezza Nuova (RE). Tutte e tre sono frane da colata, caratterizzate dalla presenza in superficie di strati di argille, e sono state studiate dal punto di vista strutturale, tra l’altro attraverso pozzi di sondaggio ed esperimenti di sismica attiva

Young workers’ access to and awareness of occupational safety and health services: age-differences and possible drivers in a large survey of employees in Italy

Young workers are in particular need of occupational safety and health (OSH) services, but it is unclear whether they have the necessary access to such services. We compared young with older workers in terms of the access to and awareness of OSH services, and examined if differences in employment conditions accounted for age-differences. We used survey data from Italy (INSuLA 1, 2014), with a sample of 8000 employed men and women aged 19 to 65 years, including 732 young workers aged under 30 years. Six questions measured access to services, and five questions assessed awareness of different OSH issues. Several employment conditions were included. Analyses revealed that young workers had less access and a lower awareness of OSH issues compared with older workers. For instance, odds ratios (OR) suggest that young workers had a 1.44 times higher likelihood [95%—confidence interval 1.21–1.70] of having no access to an occupational physician, and were more likely (2.22 [1.39–3.38]) to be unaware of legal OSH frameworks. Adjustment for selected employment conditions (company size, temporary contract) substantially reduced OR’s, indicating that these conditions contribute to differences between older and younger workers. We conclude that OSH management should pay particular attention to young workers in general and, to young workers in precarious employment, and working in small companies in particular

Expression Pattern and Biological Significance of the lncRNA ST3GAL6-AS1 in Multiple Myeloma

The biological impact of long non-coding RNAs (lncRNAs) in multiple myeloma (MM) is becoming an important aspect of investigation, which may contribute to the understanding of the complex pathobiology of the disease whilst also providing novel potential therapeutic targets. Herein, we investigated the expression pattern and the biological significance of the lncRNA ST3 beta-galactoside alpha-2,3 sialyltransferase 6 antisense RNA 1 (ST3GAL6-AS1) in MM. We documented a high ST3GAL6-AS1 expression level in MM compared to normal plasma cells (PCs) or other hematological malignancies. Transcriptome analyses of MM PCs from patients included in the CoMMpass database indicated a potential involvement of ST3GAL6-AS1 in MAPK signaling and ubiquitin-mediated proteolysis pathways. ST3GAL6-AS1 silencing by LNA-gapmeR antisense oligonucleotides inhibits cell proliferation and triggers apoptosis in MM cell line. Notably, ST3GAL6-AS1 silencing in vitro displayed the down-regulation of the MAPK pathway and protein ubiquitination. These data suggest that ST3GAL6-AS1 deregulation may play a pathogenetic role in MM by affecting both proliferation pathways and circuits fundamental for PC survival. However, ST3GAL6-AS1 expression levels seem not to be significantly associated with clinical outcome and its targeting appears to exert antagonistic effects with proteasome inhibitors used in MM. These findings strongly urge the need for further studies investigating the relevance of ST3GAL6-AS1 in MM

Expression pattern and biological significance of the lncRNA ST3GAL6-AS1 in multiple myeloma

The biological impact of long non-coding RNAs (lncRNAs) in multiple myeloma (MM) is becoming an important aspect of investigation, which may contribute to the understanding of the complex pathobiology of the disease whilst also providing novel potential therapeutic targets. Herein, we investigated the expression pattern and the biological significance of the lncRNA ST3 beta-galactoside alpha-2,3 sialyltransferase 6 antisense RNA 1 (ST3GAL6-AS1) in MM. We documented a high ST3GAL6-AS1 expression level in MM compared to normal plasma cells (PCs) or other hematological malignancies. Transcriptome analyses of MM PCs from patients included in the CoMMpass database indicated a potential involvement of ST3GAL6-AS1 in MAPK signaling and ubiquitin-mediated proteolysis pathways. ST3GAL6-AS1 silencing by LNA-gapmeR antisense oligonucleotides inhibits cell proliferation and triggers apoptosis in MM cell line. Notably, ST3GAL6-AS1 silencing in vitro displayed the down-regulation of the MAPK pathway and protein ubiquitination. These data suggest that ST3GAL6-AS1 deregulation may play a pathogenetic role in MM by affecting both proliferation pathways and circuits fundamental for PC survival. However, ST3GAL6-AS1 expression levels seem not to be significantly associated with clinical outcome and its targeting appears to exert antagonistic effects with proteasome inhibitors used in MM. These findings strongly urge the need for further studies investigating the relevance of ST3GAL6-AS1 in MM

Spin and Statistics and First Principles

It was shown in the early Seventies that, in Local Quantum Theory (that is the most general formulation of Quantum Field Theory, if we leave out only the unknown scenario of Quantum Gravity) the notion of Statistics can be grounded solely on the local observable quantities (without assuming neither the commutation relations nor even the existence of unobservable charged field operators); one finds that only the well known (para)statistics of Bose/Fermi type are allowed by the key principle of local commutativity of observables. In this frame it was possible to formulate and prove the Spin and Statistics Theorem purely on the basis of First Principles. In a subsequent stage it has been possible to prove the existence of a unique, canonical algebra of local field operators obeying ordinary Bose/Fermi commutation relations at spacelike separations. In this general guise the Spin - Statistics Theorem applies to Theories (on the four dimensional Minkowski space) where only massive particles with finite mass degeneracy can occur. Here we describe the underlying simple basic ideas, and briefly mention the subsequent generalisations; eventually we comment on the possible validity of the Spin - Statistics Theorem in presence of massless particles, or of violations of locality as expected in Quantum Gravity.Comment: Survey based on a talk given at the Meeting on "Theoretical and experimental aspects of the spin - statistics connection and related symmetries", Trieste, Italy - October 21-25, 200

Replacement of miR-155 elicits tumor suppressive activity and antagonizes bortezomib resistance in multiple myeloma

Aberrant expression of microRNAs (miRNAs) has been associated to the pathogenesis of multiple myeloma (MM). While miR-155 is considered a therapeutic target in several malignancies, its role in MM is still unclear. The analysis of miR-155 expression indicates its down-regulation in MM patient-derived as compared to healthy plasma cells, thus pointing to a tumor suppressor role in this malignancy. On this finding, we investigated miR-155 replacement as a potential anti-tumor strategy in MM. The miR-155 enforced expression triggered anti-proliferative and pro-apoptotic effects in vitro. Given the lower miR-155 levels in bortezomib-resistant as compared to sensitive MM cells, we analyzed the possible involvement of miR-155 in bortezomib resistance. Importantly, miR-155 replacement enhanced bortezomib anti-tumor activity both in vitro and in vivo in a xenograft model of human MM. In primary MM cells, we observed an inverse correlation between miR-155 and the mRNA encoding the proteasome subunit gene PSMβ5, whose dysregulation has been largely implicated in bortezomib resistance, and we validated PSMβ5 30UTR mRNA targeting, along with reduced proteasome activity, by miR-155. Collectively, our findings demonstrate that miR-155 elicits anti-MM activity, likely via proteasome inhibition, providing the framework for miR-155-based anti-MM therapeutic strategies