Use and misuse of P-values: a conditional approach to post-model-selection inference

Adaptive generation of hypotheses is among the main culprits of the lack of replicability in science. Under conditions of uncertainty, the statements, or the process that generates them, can only be trusted if the reported error rates are reflected in the replication attempts. The discrepancy between the two is due to many factors, but interactive data analysis plays a major role in the inflation of type I error. In this regard, inference after model selection is of particular interest because its misuse can be analyzed through a Monte Carlo simulation. As the findings of this thesis show, inflation of type I error can be quite severe even in low dimensional scenarios, with up to 40% of false positives in the selected set of variables. Depending on the model selection strategy and the structure of the true data-generating mechanism, this percentage varies greatly. The results of the simulation show different performances between the Least Absolute Shrinkage and Selection Operator (LASSO) and the Forward Selection (FS). In particular, the LASSO yields a type I error lower than the FS when the structure of the true data-generating mechanism is additive and a higher one when the structure is multiplicative. The results also provide additional empirical evidence that given an extensive class of problems, most methods will provide on average comparable solutions. As shown in this thesis, the conditional probability approach to selective inference represents a viable solution to control type I error while avoiding any data loss due to data splitting. In the current research environment, incentives and funding policies need to be reshaped in order to bring about effective changes on the overall reliability of the published papers, but the tools to provide rigorous results, while meeting the needs of the researchers, are available for anyone conscientious enough.Adaptive generation of hypotheses is among the main culprits of the lack of replicability in science. Under conditions of uncertainty, the statements, or the process that generates them, can only be trusted if the reported error rates are reflected in the replication attempts. The discrepancy between the two is due to many factors, but interactive data analysis plays a major role in the inflation of type I error. In this regard, inference after model selection is of particular interest because its misuse can be analyzed through a Monte Carlo simulation. As the findings of this thesis show, inflation of type I error can be quite severe even in low dimensional scenarios, with up to 40% of false positives in the selected set of variables. Depending on the model selection strategy and the structure of the true data-generating mechanism, this percentage varies greatly. The results of the simulation show different performances between the Least Absolute Shrinkage and Selection Operator (LASSO) and the Forward Selection (FS). In particular, the LASSO yields a type I error lower than the FS when the structure of the true data-generating mechanism is additive and a higher one when the structure is multiplicative. The results also provide additional empirical evidence that given an extensive class of problems, most methods will provide on average comparable solutions. As shown in this thesis, the conditional probability approach to selective inference represents a viable solution to control type I error while avoiding any data loss due to data splitting. In the current research environment, incentives and funding policies need to be reshaped in order to bring about effective changes on the overall reliability of the published papers, but the tools to provide rigorous results, while meeting the needs of the researchers, are available for anyone conscientious enough

Puppy growth rate during early periods of labrador retriever development: role of litter size and photoperiod of birth

Several studies have recently investigated the birth weight of puppies from different pure-bred dogs. In general, birth weight decreased with litter size but there has been limited investigation into factors influencing growth during early development. The first month of life includes three stages of puppy development: neonatal (0–13 days), transitional (14–20 days), and first week of socialisation period (21–28 days). The aim of this study was to evaluate bodyweight and growth rate of 120 Labrador Retriever (LR) puppies during early development. Puppies from 19 show-line bitches under standardised composition of diet during pregnancy and lactation were involved in this study. Puppies were weighed weekly from birth to 28 days using an electronic digital balance. Relative weight gain (ΔW) was calculated for the neonatal period [ΔW1 = (Wday14-Wday0)/Wday0], transition period [ΔW2 = (Wday21-Wday14)/Wday14] and first week of socialisation period [ΔW2 = (Wday28-Wday21)/Wday21]. The effects of covariates on ΔW were assessed using generalised linear mixed models. Sex and photoperiod had no impact on relative weight gain, whereas litter size had a significant effect at ΔW1 (p < .01) but not at ΔW2 and at ΔW3. Relative weight gain was slightly lower in puppies from larger litter born during short photoperiod on ΔW1. A deeper knowledge of the factors that significantly influence weight gain during the first four weeks of life could be useful for physiological and behavioural science as well as for canine breeding management.Highlights 120 Labrador Retriever puppies were weighed weekly from birth to 28 days using an electronic digital balance. Relative weight gain (ΔW) was calculated for the neonatal period (ΔW1), transition period (ΔW2) and first week of socialisation period (ΔW3). Litter size had a significant effect on relative weight gain at ΔW1 but not at ΔW2 and ΔW3. Relative weight gain was slightly lower in puppies from larger litter born during short photoperiod on ΔW1

Fogli 609-596, Termini Imerese-Capo Plaia

Il Servizio Geologico Nazionale ha unificato i Fogli 609 "Termini Imerese" e 596 "Capo Plaia" in un unico Foglio denominato 609/596 "Termini Imerese-Capo Plaia" allo scopo di uniformare i rilievi e raccoglierne la descrizione in un unico volume delle Note Illustrative. Il Foglio 609/596 "Termini Imerese-Capo Plaia" della Carta Geologica d’Italia in scala 1:50.000 è stato realizzato nell’ambito del Progetto CARG con i fondi della Legge 67/88 - Legge 226/99 con una convenzione tra Servizio Geologico Nazionale ora ISPRA) e Regione Siciliana. Le aree ricadono interamente nella Provincia di Palermo, comprendono la fascia marina del Golfo di Termini Imerese fino al promontorio di Capo Plaia, la regione dei Monti di Termini Imerese e Trabia ad ovest e il settore occidentale del gruppo montuoso delle Madonie ad est. Tra questi rilievi si sviluppa un’ampio settore collinare inciso dai fiumi Torto e Imera settentrionale (o Fiume Grande)

Epidemiology and Microbiology of Skin and Soft Tissue Infections: Preliminary Results of a National Registry

Skin and soft tissue infections (SSTIs) represent a wide range of clinical conditions characterized by a considerable variety of clinical presentations and severity. Their aetiology can also vary, with numerous possible causative pathogens. While other authors previously published analyses on several types of SSTI and on restricted types of patients, we conducted a large nationwide surveillance programme on behalf of the Italian Society of Infectious and Tropical Diseases to assess the clinical and microbiological characteristics of the whole SSTI spectrum, from mild to severe life-threatening infections, in both inpatients and outpatients. Twenty-five Infectious Diseases (ID) Centres throughout Italy collected prospectively data concerning both the clinical and microbiological diagnosis of patients affected by SSTIs via an electronic case report form. All the cases included in our database, independently from their severity, have been managed by ID specialists joining the study while SSTIs from other wards/clinics have been excluded from this analysis. Here, we report the preliminary results of our study, referring to a 12-month period (October 2016–September 2017). During this period, the study population included 254 adult patients and a total of 291 SSTI diagnoses were posed, with 36 patients presenting more than one SSTIs. The type of infection diagnosed, the aetiological micro-organisms involved and some notes on their antimicrobial susceptibilities were collected and are reported herein. The enrichment of our registry is ongoing, but these preliminary results suggest that further analysis could soon provide useful information to better understand the national epidemiologic data and the current clinical management of SSTIs in Italy

Behavior test for seven-week old puppies (Canis familiaris): Inter-rater reliability and factors associated with test performance.

Behavioral development in domestic dogs has been investigated for predicting suitability for service dog work or for matching with the "right" families as well as for identifying predispositions to behavioral problems. Findings from the scientific literature seem to confirm that conducting behavioral tests at 7 weeks of age is too early to reliably predict the temperament and personality of a dog. However, this period for domestic dogs is sensitive for early life learning and conditions during this time could have important consequences in adulthood. The aims of this study were to evaluate inter-rater reliability of a simple standardized test and to investigate which factors influence the behavioral reaction of puppies. 105 seven-week old puppies were exposed to five subtests: social attraction, following, retrieving, sudden appearance, noise. During each task, the behaviour of each pup was scored on a 3-5 point scale that reflected the suitability of the pup's reaction to the task. Scores were evaluated for a single subtest and for two aggregate indicators (i.e. response to a person: social attraction subtest and following subtest and response to object and noise: retrieving subtest, sudden appearance subtest and noise subtest). Three assessors independently scored the dogs' reactions for each task. Inter-rater reliability of the three assessors were analyzed with Fleiss' Kappa and Kendall's coefficient, which showed a high inter-rater reliability in 4 of 5 tasks. The ordered logistic regression was carried out to obtain a proportional odds model that was used to model the relationship between sex, litter size, stimulating environment, parity of mother, adequate maternal behavior and high scores. Litter size and maternal parity were associated with test performance in response to a person. The variance of effect of litter was high in response to object and noise. Taken together, our results suggest that using this scoring system there is sufficient inter-rater reliability in the test and litter size and mother experience influences task performances related to dog-human interaction

Assessment of survival in patients with idiopathic pulmonary fibrosis using quantitative HRCT indexes

Abstract Background The assessment of Idiopathic Pulmonary Fibrosis (IPF) using HRCT requires great experience and is limited by a significant inter-observer variability, even between trained radiologists. The evaluation of HRCT through automated quantitative analysis may hopefully solve this problem. The accuracy of CT-histogram derived indexes in the assessment of survival in IPF patients has been poorly studied. Methods Forty-two patients with a diagnosis of IPF and a follow up time of 3 years were retrospectively collected; HRCT and Pulmonary Function Tests (PFTs) performed at diagnosis time were analysed; the extent of fibrotic disease was quantified on HRCT using kurtosis, skewness, Mean Lung Density (MLD), High attenuation areas (HAA%) and Fibrotic Areas (FA%). Univariate Cox regression was performed to assess hazard ratios for the explored variables and a multivariate model considering skewness, FVC, DLCO and age was created to test their prognostic value in assessing survival. Through ROC analysis, threshold values demonstrating the best sensitivity and specificity in predicting mortality were identified. They were used as cut-off points to graph Kaplan-Meier curves specific for the CT-indexes. Results Kurtosis, skewness, MLD, HAA% and FA% were good predictors of mortality (HR 0.44, 0.74, 1.01, 1.12, 1.06; p = 0.03, p = 0.01, p = 0.02, p = 0.02 and p = 0.017 respectively). Skewness demonstrated the lowest Akaike’s information criterion value (55.52), proving to be the best CT variable for prediction of mortality. Significant survival differences considering proposed cut-off points were also demonstrated according to kurtosis (p = 0.02), skewness (p = 0.005), MLD (p = 0.003), HAA% (p = 0.009) and FA% (p = 0.02) – obtained from quantitative HRCT analysis at diagnosis time. Conclusions CT-histogram derived indexes may provide an accurate estimation of survival in IPF patients. They demonstrate a correlation with PFTs, highlighting their possible use in clinical practice

Characteristics and risk factors for SARS-CoV-2 in children tested in the early phase of the pandemic: a cross-sectional study, Italy, 23 February to 24 May 2020

BackgroundVery few studies describe factors associated with COVID-19 diagnosis in children.AimWe here describe characteristics and risk factors for COVID-19 diagnosis in children tested in 20 paediatric centres across Italy.MethodsWe included cases aged 0-18 years tested between 23 February and 24 May 2020. Our primary analysis focused on children tested because of symptoms/signs suggestive of COVID-19.ResultsAmong 2,494 children tested, 2,148 (86.1%) had symptoms suggestive of COVID-19. Clinical presentation of confirmed COVID-19 cases included besides fever (82.4%) and respiratory signs or symptoms (60.4%) also gastrointestinal (18.2%), neurological (18.9%), cutaneous (3.8%) and other unspecific influenza-like presentations (17.8%). In multivariate analysis, factors significantly associated with SARS-CoV-2 positivity were: exposure history (adjusted odds ratio (AOR): 39.83; 95% confidence interval (CI): 17.52-90.55; p &lt; 0.0001), cardiac disease (AOR: 3.10; 95% CI: 1.19-5.02; p &lt; 0.0001), fever (AOR: 3.05%; 95% CI: 1.67-5.58; p = 0.0003) and anosmia/ageusia (AOR: 4.08; 95% CI: 1.69-9.84; p = 0.002). Among 190 (7.6%) children positive for SARS-CoV-2, only four (2.1%) required respiratory support and two (1.1%) were admitted to intensive care; all recovered.ConclusionRecommendations for SARS-CoV-2 testing in children should consider the evidence of broader clinical features. Exposure history, fever and anosmia/ageusia are strong risk factors in children for positive SARS-CoV-2 testing, while other symptoms did not help discriminate positive from negative individuals. This study confirms that COVID-19 was a mild disease in the general paediatric population in Italy. Further studies are needed to understand risk, clinical spectrum and outcomes of COVID-19 in children with pre-existing conditions

Epidemiology, aetiology and treatment of skin and soft tissue infections: final report of a prospective multicentre national registry

Skin and soft tissue infections (SSTIs) represent a heterogenous group of pathological conditions involving the skin or the underlying subcutaneous tissues, fascia and muscle, characterised by a considerable variety of clinical presentations, severity and possible aetiological pathogens. Although previous analyses on restricted types of SSTIs and population have already been published, we conducted a large nationwide surveillance program on behalf of the Italian Society of Infectious and Tropical Diseases to assess the clinical and microbiological characteristics of the whole SSTI spectrum, from mild to severe life-threatening infections, in both inpatients and outpatients and their management. Twenty-nine Infectious Diseases (ID) Centres throughout Italy collected prospectively data concerning both the clinical and microbiological diagnosis of patients affected by SSTIs via an electronic case report form. We included in our database all cases managed by ID specialists participating to the study, independently from their severity or the setting of consultation. Here, we integrated previous preliminary results analysing and reporting data referring to a 3-year period (October 2016-October 2019). During this period, the study population included 478 adult patients with diagnosis of SSTI. The type of infection diagnosed, the aetiological agent involved and some notes on antimicrobial susceptibilities were collected and reported herein. We also analysed the most common co-morbidities, the type and duration of therapy executed, before and after ID intervention and the length of stay. The results of our study provide information to better understand the national epidemiologic data and the current clinical management of SSTIs in Italy