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Likelihood Asymptotics in Nonregular Settings: A Review with Emphasis on the Likelihood Ratio [article]

Alessandra R. Brazzale, Valentina Mameli
2022 arXiv   pre-print
This paper reviews the most common situations where one or more regularity conditions which underlie classical likelihood-based parametric inference fail. We identify three main classes of problems: boundary problems, indeterminate parameter problems--which include non-identifiable parameters and singular information matrices--and change-point problems. The review focuses on the large-sample properties of the likelihood ratio statistic, though other approaches to hypothesis testing and
more » ... ns to estimation may be mentioned in passing. We emphasize analytical solutions and acknowledge software implementations where available. Some summary insight about the possible tools to derivate the key results is given.
arXiv:2206.15178v1 fatcat:i3to5fdtsnhzrpszxte6azxzz4

Picture of the Month—Quiz Case

Chiara Mameli, Andrea E. Scaramuzza, Gian Luca Tadini, Sara Riboni, Alessandra De Palma, Gian Vincenzo Zuccotti
2009 Archives of Pediatrics & Adolescent Medicine  
Affiliations: Departments of Pediatrics, Azienda Ospedaliera, "Ospedale Luigi Sacco" (Drs Mameli, Scaramuzza, Riboni, De Palma, and Zuccotti), and Dermatology (Dr Tadini), University of Milan, Milan, Italy  ... 
doi:10.1001/archpediatrics.2009.114-a pmid:19581551 fatcat:2blvohbvg5bq7hkelryvl65lhy

Breast in vivo dosimetry by EPID

Andrea Fidanzio, Francesca Greco, Alessandra Mameli, Luigi Azario, Mario Balducci, Maria Antonietta Gambacorta, Vincenzo Frascino, Savino Cilla, Domenico Sabatino, Angelo Piermattei
2010 Journal of Applied Clinical Medical Physics  
An electronic portal imaging device (EPID) is an effective detector for in vivo transit dosimetry. In fact, it supplies two-dimensional information, does not require special efforts to be used during patient treatment, and can supply data in real time. In the present paper, a new procedure has been proposed to improve the EPID in vivo dosimetry accuracy by taking into account the patient setup variations. The procedure was applied to the breast tangential irradiation for the reconstruction of
more » ... e dose at the breast midpoint, D m . In particular, the patient setup variations were accounted for by comparing EPID images versus digitally reconstructed radiographies. In this manner, EPID transit signals were obtained corresponding to the geometrical projections of the breast midpoint on the EPID for each therapy session. At the end, the ratios R between D m and the doses computed by the treatment planning system (TPS) at breast midpoints, D m,TPS , were determined for 800 therapy sessions of 20 patients. Taking into account the method uncertainty, tolerance levels equal to ± 5% have been determined for the ratio R. PACS numbers: 87.55.Qr, 87.55.km, 87.53.Bn Key words: in vivo dosimetry, transit dosimetry, quality assurance in breast radiotherapy a
doi:10.1120/jacmp.v11i4.3275 fatcat:ibewrxpf3vgipf6zebvpefxucm

Breast in vivo dosimetry by EPID

Andrea Fidanzio, Francesca Greco, Alessandra Mameli, Luigi Azario, Mario Balducci, Maria Antonietta Gambacorta, Vincenzo Frascino, Savino Cilla, Domenico Sabatino, Angelo Piermattei
2010 Journal of Applied Clinical Medical Physics  
An electronic portal imaging device (EPID) is an effective detector for in vivo transit dosimetry. In fact, it supplies two-dimensional information, does not require special efforts to be used during patient treatment, and can supply data in real time. In the present paper, a new procedure has been proposed to improve the EPID in vivo dosimetry accuracy by taking into account the patient setup variations. The procedure was applied to the breast tangential irradiation for the reconstruction of
more » ... e dose at the breast midpoint, Dm. In particular, the patient setup variations were accounted for by comparing EPID images versus digitally reconstructed radiographies. In this manner, EPID transit signals were obtained corresponding to the geometrical projections of the breast midpoint on the EPID for each therapy session. At the end, the ratios R between D(m) and the doses computed by the treatment planning system (TPS) at breast midpoints, D(m,TPS), were determined for 800 therapy sessions of 20 patients. Taking into account the method uncertainty, tolerance levels equal to ± 5% have been determined for the ratio R.The improvement of in vivo dosimetry results obtained (taking into account patient misalignment) has been pointed out comparing the R values obtained with and with-out considering patient setup variations. In particular, when patient misalignments were taken into account, the R values were within ± 5% for 93% of the checks; when patient setup variations were not taken into account, the R values were within ± 5% in 72% of the checks. This last result points out that the transit dosimetry method overestimates the dose discrepancies if patient setup variations are not taken into account for dose reconstruction. In this case, larger tolerance levels have to be adopted as a trade-off between workload and ability to detect errors, with the drawback being that some errors (such as the ones in TPS implementation or in beam calibration) cannot be detected, limiting the in vivo dosimetry efficacy.The paper also reports preliminary results about the possibility of reconstructing a dose profile perpendicular to the beam central axis reaching from the apex to the lung and passing through the middle point of the breast by an algorithm, similar to the one used for dose reconstruction at breast midpoint. In particular, the results have shown an accuracy within ± 3% for the dose profile reconstructed in the breast (excluding the interface regions) and an underestimation of the lung dose.
pmid:21081886 pmcid:PMC5720411 fatcat:piqlky2yqnghnnlpqushogeojm

Estimation of Water Stress in Grapevines Using Proximal and Remote Sensing Methods

Alessandro Matese, Rita Baraldi, Andrea Berton, Carla Cesaraccio, Salvatore Di Gennaro, Pierpaolo Duce, Osvaldo Facini, Massimiliano Mameli, Alessandra Piga, Alessandro Zaldei
2018 Remote Sensing  
In light of climate change and its impacts on plant physiology, optimizing water usage and improving irrigation practices play a crucial role in crop management. In recent years, new optical remote sensing techniques have become widespread since they allow a non-invasive evaluation of plant water stress dynamics in a timely manner. Unmanned aerial vehicles (UAV) currently represent one of the most advanced platforms for remote sensing applications. In this study, remote and proximal sensing
more » ... urements were compared with plant physiological variables, with the aim of testing innovative services and support systems to farmers for optimizing irrigation practices and scheduling. The experiment, conducted in two vineyards located in Sardinia, Italy, consisted of two regulated deficit irrigation (RDI) treatments and two reference treatments maintained under stress and well-watered conditions. Indicators of crop water status (Crop Water Stress Index-CWSI-and linear thermal index) were calculated from UAV images and ground infrared thermal images and then related to physiological measurements. The CWSI values for moderate water deficit (RDI-1) were 0.72, 0.28 and 0.43 for 'Vermentino', 'Cabernet' and 'Cagnulari' respectively, while for severe (RDI-2) water deficit the values were 0.90, 0.34 and 0.51. The highest differences for net photosynthetic rate (Pn) and stomatal conductance (Gs) between RDI-1 and RDI-2 were observed in 'Vermentino'. The highest significant correlations were found between CWSI with Pn (R = −0.80), with Φ PSII (R = −0.49) and with Fv'/Fm' (R = −0.48) on 'Cagnulari', while a unique significant correlation between CWSI and non-photochemical quenching (NPQ) (R = 0.47) was found on 'Vermentino'. Pn, as well as the efficiency of light use by the photosystem II (PSII), declined under stress conditions and when CWSI values increased. Under the experimental water stress conditions, grapevines were able to recover their efficiency during the night, activating a photosynthetic protection mechanism such as thermal energy dissipation (NPQ) to prevent irreversible damage to the photosystem. The results presented here demonstrate that CWSI values derived from remote and proximal sensors could be valuable indicators for the assessment of the spatial variability of crop water status in Mediterranean vineyards.
doi:10.3390/rs10010114 fatcat:vbrqwd7czrbd3aqugzvxmg4xee

The Role of Pediatric Nutrition as a Modifiable Risk Factor for Precocious Puberty

Valeria Calcaterra, Elvira Verduci, Vittoria Carlotta Magenes, Martina Chiara Pascuzzi, Virginia Rossi, Arianna Sangiorgio, Alessandra Bosetti, Gianvincenzo Zuccotti, Chiara Mameli
2021 Life  
Puberty is a critical phase of growth and development characterized by a complex process regulated by the neuroendocrine system. Precocious puberty (PP) is defined as the appearance of physical and hormonal signs of pubertal development at an earlier age than is considered normal. The timing of puberty has important public health, clinical, and social implications. In fact, it is crucial in psychological and physical development and can impact future health. Nutritional status is considered as
more » ... ne of the most important factors modulating pubertal development. This narrative review presents an overview on the role of nutritional factors as determinants of the timing of sexual maturation, focusing on early-life and childhood nutrition. As reported, breast milk seems to have an important protective role against early puberty onset, mainly due to its positive influence on infant growth rate and childhood overweight prevention. The energy imbalance, macro/micronutrient food content, and dietary patterns may modulate the premature activation of the hypothalamic–pituitary–gonadal axis, inducing precocious activation of puberty. An increase in knowledge on the mechanism whereby nutrients may influence puberty will be useful in providing adequate nutritional recommendations to prevent PP and related complications.
doi:10.3390/life11121353 pmid:34947884 pmcid:PMC8706413 fatcat:ntftft6435dg3djz6go2qy3koy

The Diabetic Lung: Insights into Pulmonary Changes in Children and Adolescents with Type 1 Diabetes

Chiara Mameli, Michele Ghezzi, Alessandra Mari, Giulia Cammi, Maddalena Macedoni, Francesca Chiara Redaelli, Valeria Calcaterra, Gianvincenzo Zuccotti, Enza D'Auria
2021 Metabolites  
Historically, the lung was not listed and recognized as a major target organ of diabetic injury. The first evidence of diabetic lung involvement was published fifty years ago, with a study conducted in a population of young adults affected by type 1 diabetes (T1D). In recent years, there has been mounting evidence showing that the lung is a target organ of diabetic injury since the beginning of the disease—at the pediatric age. The deeply branched vascularization of the lungs and the abundance
more » ... f connective tissue, indeed, make them vulnerable to the effects of hyperglycemia, in a way similar to other organs affected by microvascular complications. In this review, we focus on pulmonary function impairment in children and adolescents affected by T1D. We also cover controversial aspects regarding available studies and future perspectives in this field.
doi:10.3390/metabo11020069 pmid:33530418 fatcat:27sv3ofru5bdvm6fzytr2hemae

BAX Gene Overexpression in the Tongue Could Warn of Infection Risk due to Periodontal Pathogens

Germano Orrù, Francesca Muggironi, Antonello Mameli, Cristina Demontis, Bastiana Arcadu, Alessandra Scano, Gloria Denotti, Vincenzo Piras, Carolina Girometta, Blerina Zeza, Andrea Pilloni
2018 Open Dentistry Journal  
Different host proteins play a central role in cell response during bacterial infections, the Bcl-2-Associated X protein (BAX) and Vascular Cell Adhesion Protein 1 (VCAM-1) are often reported in infective primary events during cell injury. Objective: The aim of this study is to evaluate the predictive value of these two proteins as biomarkers of oral bacterial infection, with particular emphasis on the tongue, which plays an important role in microbial homeostasis in the mouth. Methods:
more » ... ine patients were recruited and divided according to the Periodontal Index (CPI), 4 of them were severely compromised periodontal patients. Oral hygiene, gingival tissues and plaque presence were evaluated clinically. The laboratory analysis carried out on tongue tissue included: total bacterial genomes, proportion of specific periopathogens and BAX -VCAM-1 expression rate, while Reactive Oxygen Species (ROS) were measured in saliva. Results: Neither tongue microbiological status nor salivary ROS level corresponded with the state of disease. VCAM-1 mRNA expression rate was comparable in all patients but, on the contrary, BAX expression resulted high in periodontally-compromised patients and appears related to periodontal status in the analyzed subjects. Conclusion: This preliminary work suggests that the BAX protein is a possible candidate in a prognostic marker study for oral diseases started by periodontal bacteria. For example, none of the evaluated clinical and microbiological parameters could predict the presence, prognosis or recurrence of periodontal diseases. This biomarker could be a valuable tool in determining the risk, diagnosis and prognosis of this human illness.
doi:10.2174/1874210601812011070 fatcat:rrsc2hmdkfazhc2getg4vv2m6q

As(III, V) Uptake from Nanostructured Iron Oxides and Oxyhydroxides: The Complex Interplay between Sorbent Surface Chemistry and Arsenic Equilibria

Marco Sanna Angotzi, Valentina Mameli, Alessandra Fantasia, Claudio Cara, Fausto Secci, Stefano Enzo, Marianna Gerina, Carla Cannas
2022 Nanomaterials  
Iron oxides/oxyhydroxides, namely maghemite, iron oxide-silica composite, akaganeite, and ferrihydrite, are studied for AsV and AsIII removal from water in the pH range 2–8. All sorbents were characterized for their structural, morphological, textural, and surface charge properties. The same experimental conditions for the batch tests permitted a direct comparison among the sorbents, particularly between the oxyhydroxides, known to be among the most promising As-removers but hardly compared in
more » ... he literature. The tests revealed akaganeite to perform better in the whole pH range for AsV (max 89 mg g−1 at pH0 3) but to be also efficient toward AsIII (max 91 mg g−1 at pH0 3–8), for which the best sorbent was ferrihydrite (max 144 mg g−1 at pH0 8). Moreover, the study of the sorbents' surface chemistry under contact with arsenic and arsenic-free solutions allowed the understanding of its role in the arsenic uptake through electrophoretic light scattering and pH measurements. Indeed, the sorbent's ability to modify the starting pH was a crucial step in determining the removal of performances. The AsV initial concentration, contact time, ionic strength, and presence of competitors were also studied for akaganeite, the most promising remover, at pH0 3 and 8 to deepen the uptake mechanism.
doi:10.3390/nano12030326 pmid:35159671 pmcid:PMC8840107 fatcat:mpo255kbc5hs7jfm3z2tiylnqu

Efficacy and safety of a dual boosted protease inhibitor-based regimen, atazanavir and fosamprenavir/ritonavir, against HIV: experience in a pediatric population

Stefano Rusconi, Vania Giacomet, Chiara Mameli, Alessandra Viganò, Ottavia Viganò, Fulvio Adorni, Massimo Galli, Gian Vincenzo Zuccotti
2012 BMC Infectious Diseases  
Although dual-boosted protease inhibitors regimen is not recommended in children with HIV infection, such a strategy could be useful in subjects with a complex resistance profile. This study was aimed at assessing the long term efficacy and safety of a double-boosted protease inhibitor combination, fosamprenavir (fAVP) and atazanavir/ritonavir (ATV/r) in a cohort of HIV-infected children and adolescents who had failed with nucleoside reverse transcriptase inhibitors. Methods: Seven vertically
more » ... fected children and adolescents who had previously failed highly active antiretroviral therapy and were resistant to nucleoside reverse transcriptase inhibitors, received a dual protease inhibitor (PI) regimen including fAVP plus ATV/r for 42 months. The patients were assessed at baseline, every month for the first 24 weeks of therapy and every 3 months until month 32. Physical examination, CD4+ cell count, HIV-RNA viral load, lipid profile and hepatic function were assessed throughout the follow up. Results: During the study no serious adverse events were reported. CD4 absolute number increased over-time in all subjects. At baseline the median HIV-RNA was 6562 cp/mL (ranging 1048 -102772 cp/mL) and rapidly decreased below the limit of detection (50 cp/mL) after 2 months of the new treatment and remained undetectable in all cases through the entire study period. At the beginning of the study all cases showed a normal lipid profile. During the study period, 4/7 subjects showed total cholesterol, low density lipoprotein and triglyceride levels >97 th cent.le for the males and 94 th cent.le for the females. HDL cholesterol showed protective values. Hepatic enzymes remained stable during the entire observation, whereas total bilirubin showed toxicity II/III grade in 6/7 subjects. No change in fat redistribution and insulin resistance was observed. Conclusion: Dual-boosted protease inhibitor therapy was virologically and immunologically effective and it could be considered as a possible alternative to a rescue regimen in children and adolescents. However, hypercholesterolemia and hypertriglyceridemia need close follow-up and may limit the use of this therapeutic option.
doi:10.1186/1471-2334-12-179 pmid:22866946 pmcid:PMC3434076 fatcat:7cykb76k6rffxfmxz5ngg3raoi

Effects of a multidisciplinary weight loss intervention in overweight and obese children and adolescents: 11 years of experience

Chiara Mameli, Jesse C. Krakauer, Nir Y. Krakauer, Alessandra Bosetti, Chiara Matilde Ferrari, Laura Schneider, Barbara Borsani, Sara Arrigoni, Erica Pendezza, Gian Vincenzo Zuccotti, David Meyre
2017 PLoS ONE  
Krakauer, Gian Vincenzo Zuccotti. administration: Chiara Mameli. Resources: Chiara Mameli, Jesse C. Krakauer, Nir Y. Krakauer, Alessandra Bosetti, Gian Vincenzo Zuccotti.  ...  Investigation: Chiara Mameli, Alessandra Bosetti, Chiara Matilde Ferrari, Laura Schneider, Barbara Borsani, Sara Arrigoni, Erica Pendezza. Methodology: Chiara Mameli, Jesse C. Krakauer, Nir Y.  ... 
doi:10.1371/journal.pone.0181095 pmid:28704494 pmcid:PMC5509286 fatcat:3ybjttfednbuzlvx4kjxex3du4

Expression and Activation by Epstein Barr Virus of Human Endogenous Retroviruses-W in Blood Cells and Astrocytes: Inference for Multiple Sclerosis

Giuseppe Mameli, Luciana Poddighe, Alessandra Mei, Elena Uleri, Stefano Sotgiu, Caterina Serra, Roberto Manetti, Antonina Dolei, Pablo Villoslada
2012 PLoS ONE  
Proposed co-factors triggering the pathogenesis of multiple sclerosis (MS) are the Epstein Barr virus (EBV), and the potentially neuropathogenic MSRV (MS-associated retrovirus) and syncytin-1, of the W family of human endogenous retroviruses. Methodology/Principal Findings: In search of links, the expression of HERV-W/MSRV/syncytin-1, with/without exposure to EBV or to EBV glycoprotein350 (EBVgp350), was studied on peripheral blood mononuclear cells (PBMC) from healthy volunteers and MS
more » ... , and on astrocytes, by discriminatory env-specific RT-PCR assays, and by flow cytometry. Basal expression of HERV-W/MSRV/syncytin-1 occurs in astrocytes and in monocytes, NK, and B, but not in T cells. This uneven expression is amplified in untreated MS patients, and dramatically reduced during therapy. In astrocytes, EBVgp350 stimulates the expression of HERV-W/MSRV/syncytin-1, with requirement of the NF-kB pathway. In EBVgp350-treated PBMC, MSRVenv and syncytin-1 transcription is activated in B cells and monocytes, but not in T cells, nor in the highly expressing NK cells. The latter cells, but not the T cells, are activated by proinflammatory cytokines. Conclusions/Significance: In vitro EBV activates the potentially immunopathogenic and neuropathogenic HERV-W/MSRV/ syncytin-1, in cells deriving from blood and brain. In vivo, pathogenic outcomes would depend on abnormal situations, as in late EBV primary infection, that is often symptomatic, or/and in the presence of particular host genetic backgrounds. In the blood, HERV-Wenv activation might induce immunopathogenic phenomena linked to its superantigenic properties. In the brain, toxic mechanisms against oligodendrocytes could be established, inducing inflammation, demyelination and axonal damage. Local stimulation by proinflammatory cytokines and other factors might activate further HERV-Ws, contributing to the neuropathogenity. In MS pathogenesis, a possible model could include EBV as initial trigger of future MS, years later, and HERV-W/MSRV/syncytin-1 as actual contributor to MS pathogenicity, in striking parallelism with disease behaviour.
doi:10.1371/journal.pone.0044991 pmid:23028727 pmcid:PMC3459916 fatcat:hhgmjniugbhkjowgkowcxb2kem

A Curious Novel Combination of Nucleophosmin (NPM1) Gene Mutations Leading to Aberrant Cytoplasmic Dislocation of NPM1 in Acute Myeloid Leukemia (AML)

Alessandra Venanzi, Roberta Rossi, Giovanni Martino, Ombretta Annibali, Giuseppe Avvisati, Maria Grazia Mameli, Paolo Sportoletti, Enrico Tiacci, Brunangelo Falini, Maria Paola Martelli
2021 Genes  
Nucleophosmin (NPM1) mutations occurring in acute myeloid leukemia (AML) (about 50 so far identified) cluster almost exclusively in exon 12 and lead to common changes at the NPM1 mutants C-terminus, i.e., loss of tryptophans 288 and 290 (or 290 alone) and creation of a new nuclear export signal (NES), at the bases of exportin-1(XPO1)-mediated aberrant cytoplasmic NPM1. Immunohistochemistry (IHC) detects cytoplasmic NPM1 and is predictive of the molecular alteration. Besides IHC and molecular
more » ... uencing, Western blotting (WB) with anti-NPM1 mutant specific antibodies is another approach to identify NPM1-mutated AML. Here, we show that among 382 AML cases with NPM1 exon 12 mutations, one was not recognized by WB, and describe the discovery of a novel combination of two mutations involving exon 12. This appeared as a conventional mutation A with the known TCTG nucleotides insertion/duplication accompanied by a second event (i.e., an 8-nucleotide deletion occurring 15 nucleotides downstream of the TCTG insertion), resulting in a new C-terminal protein sequence. Strikingly, the sequence included a functional NES ensuring cytoplasmic relocation of the new mutant supporting the role of cytoplasmic NPM1 as critical in AML leukemogenesis.
doi:10.3390/genes12091426 pmid:34573408 pmcid:PMC8468273 fatcat:l4zr2a55uvbuzp3fwgry3yl2fu

Multiple Sclerosis and HERV-W/MSRV: A Multicentric Study

Giannina Arru, Giuseppe Mameli, Vito Astone, Caterina Serra, Yu-Min Huang, Hans Link, Enrico Fainardi, Massimiliano Castellazzi, Enrico Granieri, Miriam Fernandez, Pablo Villoslada, Maria Laura Fois (+4 others)
2007 International Journal of Biomedical Science  
We designed a large multicentric study to analyse the presence of MSRV particles in blood and CSF of a large cohort of patients and controls from different European areas. 149 MS patients and 153 neurological and healthy controls were selected from Sardinia, Spain, Northern-Italy and Sweden. To avoid biological and inter-assay variability MSRV was detected within a single laboratory through nested and real-time PCR assays specific for pol and env genes. MSRV detection in blood and CSF of MS
more » ... ents and controls in populations of different ethnicity gave significant differences (p<0.05 compared to neurological controls and <0.001 compared to healthy controls). The presence and viral load of MSRV are significantly associated with MS as compared to neurological and healthy controls in all ethnic groups.
pmid:23675056 pmcid:PMC3614662 fatcat:r3sbffsqrzegbhtiou3h66rv7q

The association between a body shape index and cardiovascular risk in overweight and obese children and adolescents

Chiara Mameli, Nir Y. Krakauer, Jesse C. Krakauer, Alessandra Bosetti, Chiara Matilde Ferrari, Norma Moiana, Laura Schneider, Barbara Borsani, Teresa Genoni, Gianvincenzo Zuccotti, Yvonne Böttcher
2018 PLoS ONE  
Project administration: Chiara Mameli, Gianvincenzo Zuccotti. Resources: Chiara Mameli, Nir Y. Krakauer, Jesse C. Krakauer, Alessandra Bosetti, Gianvincenzo Zuccotti.  ...  Investigation: Chiara Mameli, Chiara Matilde Ferrari, Norma Moiana, Laura Schneider, Barbara Borsani, Teresa Genoni. Methodology: Chiara Mameli, Nir Y. Krakauer, Jesse C. Krakauer.  ... 
doi:10.1371/journal.pone.0190426 pmid:29298340 pmcid:PMC5752028 fatcat:zzsk6kj2w5hbxo42n6krfux634
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