Aggregation Among Binary, Count, and Duration Models: Estimating the Same Quantities from Different Levels of Data

Binary, count, and duration data all code discrete events occurring at points in time. Although a single data generation process can produce all of these three data types, the statistical literature is not very helpful in providing methods to estimate parameters of the same process from each. In fact, only a single theoretical process exists for which known statistical methods can estimate the same parameters—and it is generally used only for count and duration data. The result is that seemingly trivial decisions about which level of data to use can have important consequences for substantive interpretations. We describe the theoretical event process for which results exist, based on time independence. We also derive a set of models for a time-dependent process and compare their predictions to those of a commonly used model. Any hope of understanding and avoiding the more serious problems of aggregation bias in events data is contingent on first deriving a much wider arsenal of statistical models and theoretical processes that are not constrained by the particular forms of data that happen to be available. We discuss these issues and suggest an agenda for political methodologists interested in this very large class of aggregation problems.Statistic

Methodology for the Accurate Measurement of the Power Dissipated by Braking Rheostats

The energy efficiency of transportation is a crucial point for the rail and metro system today. The optimized recovery of the energy provided by the electrical braking can lead to savings of about 10% to 30%. Such figures can be reached by infrastructure measures which allow the recovery of the breaking energy that is not directly consumed by the rail system and dissipated in rheostat resistors. A methodology for the accurate estimate of such energy is valuable for a reliable evaluation of the cost-benefit ratio associated with the infrastructural investment. The energy can be estimated by measuring a braking current flowing in the rheostats. The varying duty-cycle associated with the high dynamic variation, from zero to thousands of amperes, makes the current measurement very challenging. Moreover, the digitization of such waveforms introduces systematic errors that affect the energy estimation. To overcome these issues, this paper proposes a technique to measure the power and energy dissipated by the rheostat of a DC operated train with high accuracy. By means of an accurate model of the electrical braking circuit (chopper and rheostat) and the frequency characterization of the current transducer, a correction coefficient as a function of the duty-cycle is estimated. The method is then applied to data recorded during a measurement campaign performed on-board a 1.5 kV train of Metro de Madrid during normal operation. Using the proposed technique, the estimation of the dissipated braking energy is improved by 20%

Early anti IL-1 treatment replaces steroids in refractory Kawasaki disease: clinical experience from two case reports

Refractory Kawasaki disease (KD) is related to a major risk of coronary arteries abnormalities and its treatment is not standardized. In this regard, anakinra (ANA), an interleukin (IL)-1 receptor antagonist, represents an emerging therapeutic option. We report two cases of children, diagnosed with KD, nonresponsive to two doses of intravenous immunoglobulins, successfully treated with ANA, without a prior use of steroids. Patient 2 developed a coronary dilatation, that improved significantly after ANA therapy. Our experience highlights IL-1 blockade effectiveness in reducing KD inflammation and suggests ANA adoption as second-line therapy, with a timesaving and steroid-sparing strategy. Our results, combined with the evidence of the IL-1 key role in KD and coronary arteritis pathogenesis and to the recent clinical evidence reported by the KAWAKINRA trial, encourage an earlier recourse to ANA in patients with refractory KD, in order to fight inflammation, and to treat and prevent the development of coronary artery aneurysms. Further studies are needed to better define the place of IL-1 blockade in KD step-up treatment

Detection of SF3B1 p.Lys700Glu Mutation by PNA-PCR Clamping in Myelodysplastic Syndromes and Myeloproliferative Neoplasms

Mutations in SF3B1 are found in 20% of myelodysplastic syndromes and 5–10% of myeloproliferative neoplasms, where they are considered important for diagnosis and therapy decisions. Sanger sequencing and NGS are the currently available methods to identify SF3B1 mutations, but both are time-consuming and expensive techniques that are not practicable in most small-/medium-sized laboratories. To identify the most frequent SF3B1 mutation, p.Lys700Glu, we developed a novel fast and cheap assay based on PNA-PCR clamping. After setting the optimal PCR conditions, the limit of detection of PNA-PCR clamping was evaluated, and the method allowed up to 0.1% of mutated SF3B1 to be identified. Successively, PNA-PCR clamping and Sanger sequencing were used to blind test 90 DNA from patients affected by myelodysplastic syndromes and myeloproliferative neoplasms for the SF3B1 p.Lys700Glu mutation. PNA-PCR clamping and Sanger sequencing congruently identified 75 negative and 13 positive patients. Two patients identified as positive by PNA-PCR clamping were missed by Sanger analysis. The discordant samples were analyzed by NGS, which confirmed the PNA-PCR clamping result, indicating that these samples contained the SF3B1 p.Lys700Glu mutation. This approach could easily increase the characterization of myelodysplastic syndromes and myeloproliferative neoplasms in small-/medium-sized laboratories, and guide patients towards more appropriate therapy

HYGIENIC EVALUATIONS AND LISTERIA MONOCYTOGENES BEHAVIOUR IN THE PRODUCTION OF 'NDUJA DI SPILINGA

The aim of this work was to study the hygienic and qualitative parameters of a traditional meat product from Calabria, named 'Nduja di Spilinga, characterised by an high amount in fat (50%) and chilli pepper (25%). In this regard, 30 products, weight 500g, were prepared with and without chilli pepper (respectively, p-series: 15 products and np-series:15 products) and analysed for the count of Enterobacteria (Ent), Lactic Acid Bacteria (LAB), Gram+Catalase+Cocci (GCC+) and Yeasts. Furthermore pH, aw and Free Fatty Acids (FFA), expressed as percentage of oleic acid on 100g of total fat (TF), were evaluated. Finally, in order to estimate the potential compliance with the Regulation (EC) 2073/05 and further modifications, a challenge test for Listeria monocytogenes was carried out. Obtained data show a high decrease, during the seasoning, of Enterobacteria and L. monocytogenes especially in samples of pseries, according to their lower pH values than np-series samples. With regard to the microflora of technological interest, Yeast were the only population which significantly increases during the seasoning of p-series products, presumably influencing the increase of FFA which reached the highest concentration (5.75% oleic acid/TF) at the same time in which Yeasts reached maximum population density (17th day)

Iron overload alters the energy metabolism in patients with myelodysplastic syndromes: results from the multicenter FISM BIOFER study

Myelodysplastic syndromes (MDS) are hematological malignancies characterized by ineffective hematopoiesis and increased apoptosis in the bone marrow, which cause peripheral cytopenia. Mitochondria are key regulators of apoptosis and a site of iron accumulation that favors reactive oxygen species (ROS) production with detrimental effects on cell survival. Although the energy metabolism could represent an attractive therapeutic target, it was poorly investigated in MDS. The purpose of the study was to analyze how the presence of myelodysplastic hematopoiesis, iron overload and chelation impact on mitochondrial metabolism. We compared energy balance, OxPhos activity and efficiency, lactic dehydrogenase activity and lipid peroxidation in mononuclear cells (MNCs), isolated from 38 MDS patients and 79 healthy controls. Our data show that ATP/AMP ratio is reduced during aging and even more in MDS due to a decreased OxPhos activity associated with an increment of lipid peroxidation. Moreover, the lactate fermentation enhancement was observed in MDS and elderly subjects, probably as an attempt to restore the energy balance. The biochemical alterations of MNCs from MDS patients have been partially restored by the in vitro iron chelation, while only slight effects were observed in the age-matched control samples. By contrast, the addition of iron chelators on MNCs from young healthy subjects determined a decrement in the OxPhos efficiency and an increment of lactate fermentation and lipid peroxidation. In summary, MDS-MNCs display an altered energy metabolism associated with increased oxidative stress, due to iron accumulation. This condition could be partially restored by iron chelatio

Effects of immunomodulatory treatment with subcutaneous interferon beta-1a oncognitive decline in mildly disabled patients with relapsing-remitting multiple sclerosis

The objective of this study was to assess the effects of subcutaneous (sc) interferon beta-1a (IFNbeta-1a) on cognition in mildly disabled patients with relapsing-remitting multiple sclerosis (RRMS). Patients aged 18-50 years with RRMS (McDonald criteria; Expanded Disability Status Scale score <or=4.0) were assigned IFNbeta therapy at the physician's discretion and underwent standardized magnetic resonance imaging, neurological examination and neuropsychological testing at the baseline and regular intervals for up to three years. This analysis included 459 patients who received sc IFNbeta-1a (44 mcg: n = 236; 22 mcg: n = 223; three-year follow up was available for 318 patients). The hazard ratio for cognitive impairment over three years (44 mcg versus 22 mcg) was 0.68 (95% confidence interval [CI]: 0.480-0.972), suggesting a 32% lower risk with the higher dose treatment. At year 3, the proportion of patients who were cognitively impaired increased slightly from 23.5% at the baseline to 24.8% in the IFNbeta-1a 22 mcg treatment group, but remained stable at 15.2% in the IFNbeta-1a 44 mcg treatment group. The proportion of patients with cognitive impairment at year 3 was significantly higher in the 22 mcg group than in the 44 mcg group (P = 0.03), although a trend was also seen at the baseline (P = 0.058). Multivariate logistic regression (corrected for baseline cognitive deficits) indicated that treatment with the higher dose of IFNbeta-1a was predictive of lower cognitive impairment at three years (odds ratio: 0.51, 95% CI: 0.26-0.99) compared with the lower dose of IFNbeta-1a. These findings suggest that sc IFNbeta-1a may have dose-dependent cognitive benefits in mildly disabled patients with RRMS, and may support early initiation of high-dose IFNbeta-1a treatment

Quality of life, depression and fatigue in mildly disabled patients with relapsing-remitting multiple sclerosis receiving subcutaneous interferon beta-1a: 3-year results from the COGIMUS (COGnitive Impairment in MUltiple Sclerosis) study.

BACKGROUND: The precise relationships among quality of life, depression, fatigue and cognitive impairment in multiple sclerosis (MS) are complex and poorly understood. OBJECTIVE: To assess the effects of subcutaneous interferon beta-1a on quality of life, depression and fatigue over 3 years in the COGIMUS study, and to examine the relationship between these outcomes and baseline cognitive status. METHODS: COGIMUS was an observational 3-year trial assessing cognitive function in 459 patients with relapsing-remitting MS treated with subcutaneous interferon beta-1a. RESULTS: In total, 331 patients completed the study (168 received interferon beta-1a, 44 µg subcutaneously three times weekly, and 163 received interferon beta-1a, 22 µg subcutaneously three times weekly). Mean MS Quality of Life-54 (MSQoL-54) composite scores did not change over time. There were no significant differences between groups in MSQoL-54 composite scores when patients were grouped by treatment dose and baseline cognitive status. Mean (standard deviation) Hamilton Depression Rating Scale score decreased from 6.8 (4.9) at baseline to 5.8 (5.9) at year 3. Mean total Fatigue Impact Scale scores were low (<30) at all time points. CONCLUSION: Quality of life, depression and fatigue remained largely stable over 3 years; no effects of treatment dose or baseline cognitive status were found