The influence of affective factors on time perception

Several studies have suggested that both affective valence and arousal affect the perception of time. How-ever, in previous experiments these two affective dimensions were not systematically controlled. In the present study, a set of emotional slides rated for valence and arousal (International Affective Picture System) were projected to two groups of subjects for 2, 4 and 6 sec. One group estimated the duration on an analog scale and a second group reproduced the interval by pushing a button. Heart rate and skin conductance responses were also recorded. A highly significant valence by arousal interaction affected duration judg-ments. For low arousal stimuli, the duration of negative slides was judged relatively shorter than the duration of positive slides. For high arousal stimuli, the duration of negative slides was judged longer than the dura-tion of positive slides. These results are interpreted within a model of action tendency, in which the level of arousal controls two different motivational mechanisms, one emotional and the other attentional

A model independent safeguard for unbinned Likelihood

We present a universal method to include residual un-modeled background shape uncertainties in likelihood based statistical tests for high energy physics and astroparticle physics. This approach provides a simple and natural protection against mismodeling, thus lowering the chances of a false discovery or of an over constrained confidence interval, and allows a natural transition to unbinned space. Unbinned likelihood allows optimal usage of information for the data and the models, and enhances the sensitivity. We show that the asymptotic behavior of the test statistic can be regained in cases where the model fails to describe the true background behavior, and present 1D and 2D case studies for model-driven and data-driven background models. The resulting penalty on sensitivities follows the actual discrepancy between the data and the models, and is asymptotically reduced to zero with increasing knowledge

Performance of Drift-Tube Detectors at High Counting Rates for High-Luminosity LHC Upgrades

The performance of pressurized drift-tube detectors at very high background rates has been studied at the Gamma Irradiation Facility (GIF) at CERN and in an intense 20 MeV proton beam at the Munich Van-der-Graaf tandem accelerator for applications in large-area precision muon tracking at high-luminosity upgrades of the Large Hadron Collider (LHC). The ATLAS muon drifttube (MDT) chambers with 30 mm tube diameter have been designed to cope with and neutron background hit rates of up to 500 Hz/square cm. Background rates of up to 14 kHz/square cm are expected at LHC upgrades. The test results with standard MDT readout electronics show that the reduction of the drift-tube diameter to 15 mm, while leaving the operating parameters unchanged, vastly increases the rate capability well beyond the requirements. The development of new small-diameter muon drift-tube (sMDT) chambers for LHC upgrades is completed. Further improvements of tracking efficiency and spatial resolution at high counting rates will be achieved with upgraded readout electronics employing improved signal shaping for high counting rates

Role of miR-34a-5p in Hematopoietic Progenitor Cells Proliferation and Fate Decision: Novel Insights into the Pathogenesis of Primary Myelofibrosis

Primary Myelofibrosis (PMF) is a chronic Philadelphia-negative myeloproliferative neoplasm characterized by a skewed megakaryopoiesis and an overproduction of proinflammatory and profibrotic mediators that lead to the development of bone marrow (BM) fibrosis. Since we recently uncovered the upregulation of miR-34a-5p in PMF CD34+ hematopoietic progenitor cells (HPCs), in order to elucidate its role in PMF pathogenesis here we unravelled the effects of miR-34a-5p overexpression in HPCs. We showed that enforced expression of miR-34a-5p partially constrains proliferation and favours the megakaryocyte and monocyte/macrophage commitment of HPCs. Interestingly, we identified lymphoid enhancer-binding factor 1 (LEF1) and nuclear receptor subfamily 4, group A, member 2 (NR4A2) transcripts as miR-34a-5p-targets downregulated after miR-34a-5p overexpression in HPCs as well as in PMF CD34+ cells. Remarkably, the knockdown of NR4A2 in HPCs mimicked the antiproliferative effects of miR-34a-5p overexpression, while the silencing of LEF1 phenocopied the effects of miR-34a-5p overexpression on HPCs lineage choice, by favouring the megakaryocyte and monocyte/macrophage commitment. Collectively our data unravel the role of miR-34a-5p in HPCs fate decision and suggest that the increased expression of miR-34a-5p in PMF HPCs could be important for the skewing of megakaryopoiesis and the production of monocytes, that are key players in BM fibrosis in PMF patients

miR-494-3p overexpression promotes megakaryocytopoiesis in primary myelofibrosis hematopoietic stem/progenitor cells by targeting SOCS6

Primary myelofibrosis (PMF) is a chronic Philadelphia-negative myeloproliferative neoplasm characterized by hematopoietic stem cell-derived clonal myeloproliferation, involving especially the megakaryocyte lineage. To better characterize how the altered expression of microRNAs might contribute to PMF pathogenesis, we have previously performed the integrative analysis of gene and microRNA expression profiles of PMF hematopoietic stem/progenitor cells (HSPCs), which allowed us to identify miR- 494-3p as the upregulated microRNA predicted to target the highest number of downregulated mRNAs. To elucidate the role of miR-494-3p in hematopoietic differentiation, in the present study we demonstrated that miR-494-3p enforced expression in normal HSPCs promotes megakaryocytopoiesis. Gene expression profiling upon miR-494-3p overexpression allowed the identification of genes commonly downregulated both after microRNA overexpression and in PMF CD34+ cells. Among them, suppressor of cytokine signaling 6 (SOCS6) was confirmed to be a miR-494-3p target by luciferase assay. Western blot analysis showed reduced level of SOCS6 protein as well as STAT3 activation in miR-494-3p overexpressing cells. Furthermore, transient inhibition of SOCS6 expression in HSPCs demonstrated that SOCS6 silencing stimulates megakaryocytopoiesis, mimicking the phenotypic effects observed upon miR-494-3p overexpression. Finally, to disclose the contribution of miR-494-3p upregulation to PMF pathogenesis, we performed inhibition experiments in PMF HSPCs, which showed that miR-494-3p silencing led to SOCS6 upregulation and impaired megakaryocyte differentiation. Taken together, our results describe for the first time the role of miR-494- 3p during normal HSPC differentiation and suggest that its increased expression, and the subsequent downregulation of its target SOCS6, might contribute to the megakaryocyte hyperplasia commonly observed in PMF patients

miRNA-mRNA integrative analysis in primary myelofibrosis CD34+ cells: role of miR-155/JARID2 axis in abnormal megakaryopoiesis

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by megakaryocyte (MK) hyperplasia, bone marrow fibrosis, and abnormal stem cell trafficking. PMF may be associated with somatic mutations in JAK2, MPL, or CALR. Previous studies have shown that abnormal MKs play a central role in the pathophysiology of PMF. In this work, we studied both gene and microRNA (miRNA) expression profiles in CD34(+) cells from PMF patients. We identified several biomarkers and putative molecular targets such as FGR, LCN2, and OLFM4. By means of miRNA-gene expression integrative analysis, we found different regulatory networks involved in the dysregulation of transcriptional control and chromatin remodeling. In particular, we identified a network gathering several miRNAs with oncogenic potential (eg, miR-155-5p) and targeted genes whose abnormal function has been previously associated with myeloid neoplasms, including JARID2, NR4A3, CDC42, and HMGB3. Because the validation of miRNA-target interactions unveiled JARID2/miR-155-5p as the strongest relationship in the network, we studied the function of this axis in normal and PMF CD34(+) cells. We showed that JARID2 downregulation mediated by miR-155-5p overexpression leads to increased in vitro formation of CD41(+) MK precursors. These findings suggest that overexpression of miR-155-5p and the resulting downregulation of JARID2 may contribute to MK hyperplasia in PMF

Ecological Momentary Assessment and Intervention Principles for the Study of Awake Bruxism Behaviors, Part 1 : General Principles and Preliminary Data on Healthy Young Italian Adults

Background: Awake bruxism (AB) is an oral condition that has some uncertainties concerning the epidemiology, also due to the different diagnostic strategies that have been adopted to address it in the research setting. The recent new definition of AB suggests that an ecological momentary assessment (EMA), which enables real-time reporting of the condition under study, can implement knowledge on the topic. Objectives: This article will discuss the general principles of EMA and EMI (Ecological Momentary Intervention) and comment on a preliminary dataset gathered with a smartphone application in a population of Italian young adults. Materials and Methods: A dedicated smartphone application has been used (BruxApp (R)) on a sample of 30 University students (mean age 24 +/- 3.5 years) to record real time report on five specific oral conditions (relaxed jaw muscles, tooth contact, teeth clenching, teeth grinding, mandible bracing) that are related with the spectrum of AB activities. Data were recorded over a 7-day period for two times, with a 1-month interval between the two observation periods. The purpose of collecting data over a second week, 1-month later, was to monitor AB behaviors over time, and test for potential "EMI" effects. Results: Over the first 7 days (T1), the average frequency of relaxed jaw muscles reports at the population level was 62%. Teeth contact (20%) and mandible bracing (14%) were the most frequent AB behaviors. No significant gender differences were detected. One month later, during the second week of data collection (T2), the frequency of the conditions was as follows: relaxed jaw muscles 74%, teeth contact 11% and mandible bracing 13%. Conclusions: These data recorded do not allow any generalization due the unrepresentativeness of the study population. On the other hand, they can be used as templates for future comparisons to get deeper into the study of natural fluctuations of AB behaviors as well as into the potential biofeedback effect of an ecological momentary assessment/intervention. It is important to recognize that the use of smartphone technology may help to set range of values for AB frequency in otherwise healthy individuals, in order to stand as comparisons for selected populations with risk or associated factors.Peer reviewe

The development and pilot testing of the OroFacial Awakening Symptoms Questionnaire (OFASQ)

Background: The evolution of concepts that have featured the last decade in the field of bruxism led to the necessity of providing clinicians and researchers with adequate tools for the assessment of bruxism, such as the Standardized Tool for the Assessment of Bruxism (STAB) and the BruxScreen. The former is a multidimensional evaluation tool for the evaluation of bruxism status, while the latter is an instrument that could potentially find its applicability in large-scale epidemiological research projects for screening purposes. However, both tools lack the evaluation of orofacial symptoms at awakening, which can be predictive of temporomandibular disorders (TMDs) pain intensity and prognosis. The aim of this paper is to discuss the development of a novel tool, the OroFacial Awakening Symptoms Questionnaire (OFASQ). This questionnaire could be integrated into the STAB to investigate the presence of orofacial symptoms upon awakening and enhance knowledge of the relationship between sleep-time bruxism activities and potential clinical consequences. The OFASQ consists of a preliminary screening question about the presence or absence of a series of orofacial symptoms upon awakening and five items that evaluate the amount of pain and impairment they cause. Methods: For pilot testing, the OFASQ was administered to a diverse group of 85 subjects, including dental practitioners of various specialties, postgraduate and undergraduate dentistry students and patients. Results: Following the face validity and pilot testing phase, it emerged that OFASQ could represent a valid tool for quantifying the intensity and severity of orofacial symptoms upon awakening in everyday clinical practice. Conclusions: The OFASQ tool is considered ready for more in-depth clinical testing. The authors do not exclude the possibility of minor editing to the tool following further, more in-depth tests

Ecological Momentary Assessment and Intervention Principles for the Study of Awake Bruxism Behaviors, Part 2 : Development of a Smartphone Application for a Multicenter Investigation and Chronological Translation for the Polish Version

Objectives: The aim is to describe the process of translating the smartphone application BruxApp into Polish within the context of an ongoing multicenter project on awake bruxism (AB) epidemiology. Material and Methods: An ongoing cooperation involving 11 universities is based on the adoption of the smartphone-based EMA protocol to collect real time report of AB behaviors in the natural environment. The English version of BruxApp is adopted as a template for the multi-language translation, according to a step-by-step procedure led by mother-tongue experts in the field. A dedicated web platform for translation (viz., POEditor) is used. The process of translation into Polish is here described as an example. Results: There are two software versions available, viz., BruxApp and BruxApp Research. For both versions, back translation from Polish to English was performed to verify the accuracy of the translation procedure. The validity of the translation has been confirmed by the perfect agreement between the original and back-translated English versions, and the Polish version of BruxApp can thus be introduced in the clinical and research setting to get deeper into the study of AB epidemiology in Poland. Conclusions: As far as clinical studies are concerned, the described strategy to record data can be very useful -patients can acknowledge their habits, monitor changes over time, and implement remedial measures. In the field of research, BruxApp makes possible to collect and store a huge amount of data about the epidemiology of different forms of awake bruxism, both at the individual level and at the population level.Peer reviewe

Self-reported mandible bracing and teeth clenching are associated with anxiety and depression traits in a group of healthy young individuals

To assess the correlation between awake bruxism (AB) behaviors and psychological status in a group of healthy young adults. Participants were recruited at the University of Siena, Siena, Italy, by advertising the initiative. The reported frequency of AB behaviors was evaluated through the Oral Behavior Checklist (OBC). The 4-item Patient Health Questionnaire-4 (PHQ-4) was adopted to evaluate the participants’ psychological status. Student’s t-test was used to detect differences between genders. The Pearson correlation test was performed to assess the correlation between the two questionnaires. Mandible bracing showed the strongest correlation with anxiety and depression traits (r = 0.62), followed by teeth clenching (r = 0.54). Teeth contact (r = 0.33) and teeth grinding (r = 0.32) had the lowest level of correlation. In a sample of healthy young individuals, there is a moderate-to-high correlation between the reported teeth clenching and mandible bracing frequency and the degree of anxiety and depression symptoms. Such findings suggest the importance of the psychological assessment in awake bruxers