Effects of maternal psychological distress and perception of COVID-19 on prenatal attachment in a large sample of Italian pregnant women

Background: Evidence concerning the impact of COVID-19-related stress exposure on prenatal attachment in pregnant women is unknown. In this study we sought to assess the effect of psychological distress and risk perception of COVID-19 on prenatal attachment in a Italian sample of pregnant women. Methods: 1179 pregnant women completed an anonymous online survey and self-report questionnaires measuring socio-demographic and obstetric characteristics, psychological distress (STAI Form Y-1-2 and BDI-II), prenatal attachment (PAI) and risk perception of COVID-19. Data were collected from March 2020 to April 2020 referring to the national lockdown period. Results: After adjusting for the socio-de…

The determination of maturity stages in male elasmobranchs (Chondrichthyes) using a segmented regression of clasper length on total length

A novel statistical method for estimating the stages of maturity in male sharks and skates based on a segmented regression (SRM) is proposed. We hypothesize that this method is able to find the transition points in the three-phase relationship between total length (TL) and clasper length (CL). We applied an SRM to TL–CL data of nine species, from large pelagic sharks (e.g., Carcharhinus falciformis) to small coastal skates (e.g., Rioraja agassizi), captured in the southwestern Atlantic and northeastern Pacific. As expected, SRM detected two breakpoints, defining three maturity stages (immature, maturing, and mature), in six out of nine species. For three species, it was not possible to fin…

Improvement of wound healing after hemorrhoidectomy: a double-blind, randomized study of botulinum toxin injection.

PURPOSE: Hemorrhoidectomy is usually associated with significant pain during the postoperative period. The spasm of the internal sphincter seems to play in important role in the origin of pain. This study was designed to evaluate the effectiveness of intrasphincter injection of botulinum toxin after hemaorrhoidectomy in reducing the maximum testing pressure of the anal canal, accelerating wound healing, and decreasing postoperative pain when resting and during defecation. METHODS: Thirty patients with hemorrhoids of third and fourth degree were included in the study and randomized in two groups. Anorectal manometry was performed preoperatively and 5 and 30 days afterward ill all patients un…

Segmented relationships to model erosion of regression effect in Cox regression

In this article we propose a parsimonious parameterisation to model the so-called erosion of the covariate effect in the Cox model, namely a covariate effect approaching to zero as the follow-up time increases. The proposed parameterisation is based on the segmented relationship where proper constraints are set to accomodate for the erosion. Relevant hypothesis testing is discussed. The approach is illustrated on two historical datasets in the survival analysis literature, and some simulation studies are presented to show how the proposed framework leads to a test for a global effect with good power as compared with alternative procedures. Finally, possible generalisations are also present…

Frequent Alteration of the Yin Yang 1/Raf-1 Kinase Inhibitory Protein Ratio in Hepatocellular Carcinoma

The transcription factor Yin Yang 1 (YY1) can favor several aspects of tumorigenesis. In turn, Raf-1 Kinase Inhibitor Protein (RKIP) inhibits the oncogenic activities of MAPK and NF-κB pathways and promotes drug-induced apoptosis. Mutual influences between YY1 and RKIP may exist, and there are already separate evidences that relevant increases in YY1 and reductions in RKIP occur in hepatocellular carcinoma (HCC). However, the levels of the two factors have never been concomitantly examined in HCC. We evaluated by RT-PCR the mRNA levels of YY1, YY1AP, RKIP, and survivin in 35 clinical HCCs (91% HCV-related), in their adjacent cirrhotic tissues and in 6 healthy livers. Immunohistochemical ana…

Cardiovascular dysfunction and vitamin D status in childhood acute lymphoblastic leukemia survivors

Vitamin D (25-OHD) has a role in bone health after treatment for cancer. 25-OHD deficiency has been associated with risk factors for cardiovascular disease, but no data focusing on this topic in childhood cancer survivors have been published. We investigated the 25-OHD status in children treated for acute lymphoblastic leukemia (ALL), and evaluated its influence on vascular function. 25-OHD levels were evaluated in 52 ALL survivors and 40 matched healthy controls. Patients were grouped according to 25-OHD level (< 20 ng/m or ≥ 20 ng/ml). Auxological parameters, biochemical and hemostatic markers of endothelial function (AD, HMW-AD, ET-1, vWFAg, TAT, D-dimers, Fbg, and hs-CRP), ultrasound ma…

Quantile regression via iterative least squares computations

We present an estimating framework for quantile regression where the usual L 1-norm objective function is replaced by its smooth parametric approximation. An exact path-following algorithm is derived, leading to the well-known ‘basic’ solutions interpolating exactly a number of observations equal to the number of parameters being estimated. We discuss briefly possible practical implications of the proposed approach, such as early stopping for large data sets, confidence intervals, and additional topics for future research.

Heat tolerance and outdoor temperature in early life, among Italian migrants in Turin–Italy

Trajectories of Blood Pressure Elevation Preceding Hypertension Onset: An Analysis of the Framingham Heart Study Original Cohort

Importance Given that hypertension remains a leading risk factor for chronic disease globally, there are substantial ongoing efforts to define the optimal range of blood pressure (BP). Objective To identify a common threshold level above which BP rise tends to accelerate in progression toward hypertension. Design, Setting, and Participants This longitudinal, community-based epidemiological cohort study of adults enrolled in Framingham, Massachusetts, included 1252 participants (mean [SD] age, 35.3 [2.7] years) from the Framingham Original Cohort, of whom 790 (63.1%) were women. Each participant contributed up to 28 serial examinations of standardized resting BP measurements between 1948 and…

The “ThreePlusOne” Likelihood-Based Test Statistics: Unified Geometrical and Graphical Interpretations

The presentation of the well known Likelihood Ratio, Wald and Score test statistics in textbooks appears to lack a unified graphical and geometrical interpretation. We present two simple graphical representations on a common scale for these three test statistics, and also the recently proposed Gradient test statistic. These unified graphical displays may favour better understanding of the geometrical meaning of the likelihood based statistics and provide useful insights into their connections.

Growth factors and IL-17 in hereditary angioedema

Hereditary angioedema (HAE) is a rare autosomal dominant disorder, due to C1-inhibitor deficiency, which causes episodic swellings of subcutaneous tissues, bowel walls and upper airways which are disabling and potentially life-threatening. We evaluated n = 17 patients with confirmed HAE diagnosis in basal and crisis state and n = 19 healthy subjects. The samples were tested for IL-17, FGFb, G-CSF and GM-CSF, using Bio-plex kit. Data analysis was performed via nonparametric Spearman’s correlations and two sets of linear mixed models. When comparing HAE subjects during basal and crisis states, we found out significantly (i.e., p value <0.05) higher values in crisis states rather than in basal…

The complex alteration in the network of IL-17-type cytokines in patients with hereditary angioedema

Hereditary angioedema (HAE) is a rare autosomic-dominant disorder characterized by a deficiency of C1 esterase inhibitor which causes episodic swellings of subcutaneous tissues, bowel walls and upper airways that are disabling and potentially life-threatening. We evaluated n = 17 patients with confirmed HAE diagnosis during attack and remission state and n = 19 healthy subjects. The samples were tested for a panel of IL (Interleukin)-17-type cytokines (IL-1β, IL-6, IL-10, granulocyte–macrophage colony stimulating factor (GM-CSF), IL-17, IL-21, IL-22, IL-23) and transforming growth factor-beta (TGF-β) subtypes. Data indicate that there are variations of cytokine levels in HAE subjects compar…

A flexible approach to the crossing hazards problem

We propose a simple and flexible framework for the crossing hazards problem. The method is not confined to two-sample problems, but may also work with continuous exposure variables whose effect changes its sign at some time-point of the observed follow-up time. Penalized partial likelihood estimation relies upon the assumption of a smooth hazard ratio via low-rank basis splines with a conventional difference penalty to ensure smoothness, and additional ad hoc penalties to obtain restricted estimates useful in the context of crossing hazards. The framework naturally also leads to a statistical test that has good power for revealing a global effect under several alternatives, including crossi…

Fitting generalized linear models with unspecified link function: A P-spline approach

Generalized linear models (GLMs) outline a wide class of regression models where the effect of the explanatory variables on the mean of the response variable is modelled throughout the link function. The choice of the link function is typically overlooked in applications and the canonical link is commonly used. The estimation of GLMs with unspecified link function is discussed, where the linearity assumption between the link and the linear predictor is relaxed and the unspecified relationship is modelled flexibly by means of P-splines. An estimating algorithm is presented, alternating estimation of two working GLMs up to convergence. The method is applied to the analysis of quit behavior of…

Modelling the non-linear multiple-lag effects of ambient temperature on mortality in Santiago and Palermo: a constrained segmented distributed lag approach

Objectives: Exposure to ambient temperature can affect mortality levels for days or weeks following exposure, making modelling such effects in regression analysis of daily time-series data complex. Methods: We propose a new approach involving a multi-lag segmented approximation to account for the non-linear effect of temperature and the use of two different penalised spline bases to model the distributed lag of both heat and cold exposure. Compared with standard splines, the novel penalised framework is more flexible at short lags where change in coefficients is greatest, and selection of the maximum lag appears substantially less important in determining the overall pattern of the effect. …

Influential Periods in Longitudinal Clinical Cardiovascular Health Scores

Abstract The prevalence of ideal cardiovascular health (CVH) among adults in the United States is low and decreases with age. Our objective was to identify specific age windows when the loss of CVH accelerates, to ascertain preventive opportunities for intervention. Data were pooled from 5 longitudinal cohorts (Project Heartbeat!, Cardiovascular Risk in Young Finns Study, The Bogalusa Heart Study, Coronary Artery Risk Development in Young Adults, Special Turku Coronary Risk Factor Intervention Project) from the United States and Finland from 1973 to 2012. Individuals with clinical CVH factors (i.e., body mass index, blood pressure, cholesterol, blood glucose) measured from ages 8 to 55 year…

A note on temperature effect estimate in mortality time series analysis

Bivariate Distributed Lag Models for the analysis of temperature-by-pollutant interaction effect on mortality.

This paper introduces Bivariate Distributed Lags Models (BDLMs) to investigate synergic effect of temperature and airborne particles on mortality. These models seem particulary attractive since they allow to model interactions between such environmental variables accounting for possible delayed effects. A B-spline framework is used to approximate the coefficient surface of the temperature-by-pollutant interaction and possible alternatives are also discussed. A case study of mortality time-series data in Palermo, Italy, is presented to illustrate the model. Copyright © 2007 John Wiley & Sons, Ltd.

Multiple smoothing parameters selection in additive regression quantiles

We propose an iterative algorithm to select the smoothing parameters in additive quantile regression, wherein the functional forms of the covariate effects are unspecified and expressed via B-spline bases with difference penalties on the spline coefficients. The proposed algorithm relies on viewing the penalized coefficients as random effects from the symmetric Laplace distribution, and it turns out to be very efficient and particularly attractive with multiple smooth terms. Through simulations we compare our proposal with some alternative approaches, including the traditional ones based on minimization of the Schwarz Information Criterion. A real-data analysis is presented to illustrate t…

18-yr cumulative incidence of respiratory/allergic symptoms/diseases and risk factors in the Pisa epidemiological study

Abstract Background Few population-based studies on the effects of environmental exposure variation exist. Aim Assessing respiratory symptom/disease incidence related to risk factor exposure changes. Methods A longitudinal general population sample from two surveys (PISA2:1991–1993; PISA3:2009–2011; no. = 970), aged ≥20 years at baseline, completed a questionnaire on respiratory symptoms/diseases, risk factor exposure and performed spirometry. 18-year follow-up cumulative incidence of respiratory symptoms/diseases and longitudinal changes (persistence, incidence, remittance) in risk factor exposure were computed. Results Cumulative incidence values were: 3.2% (corresponding to a 1.8‰/year i…

Efficient change point detection in genomic sequences of continuous measurements

Abstract Motivation: Knowing the exact locations of multiple change points in genomic sequences serves several biological needs, for instance when data represent aCGH profiles and it is of interest to identify possibly damaged genes involved in cancer and other diseases. Only a few of the currently available methods deal explicitly with estimation of the number and location of change points, and moreover these methods may be somewhat vulnerable to deviations of model assumptions usually employed. Results: We present a computationally efficient method to obtain estimates of the number and location of the change points. The method is based on a simple transformation of data and it provides re…

A model-based approach for assessing bronchodilator responsiveness in children: The conventional cutoff revisited

An increase in FEV1 >=12% has been proposed in international guidelines as a clue to airway reversibility for diagnosing asthma in both adults and children. However, the validity of this cut-off has been questioned in the pediatric population. The aim of this study was to provide evidence that different cut-off values in BDR may be associated with better performance in discriminating among outpatient children with naïve asthma (A) and without asthma (NA). We compared three approaches: i) the conventional cutoff (12%); ii) the cut-off estimated by Youden's criteria; and iii) the cut-off based on a model-driven approach. we found that the conventional cut-off of 12% showed poor sensitivity in…

A segmented regression model for event history data: an application to the fertility patterns in Italy

We propose a segmented discrete-time model for the analysis of event history data in demographic research. Through a unified regression framework, the model provides estimates of the effects of explanatory variables and jointly accommodates flexibly non-proportional differences via segmented relationships. The main appeal relies on ready availability of parameters, changepoints, and slopes, which may provide meaningful and intuitive information on the topic. Furthermore, specific linear constraints on the slopes may also be set to investigate particular patterns. We investigate the intervals between cohabitation and first childbirth and from first to second childbirth using individual data …

The effect of birthplace on heat tolerance and mortality in Milan, Italy, 1980-1989

The temperature–mortality relationship follows a well-known J-V shaped pattern with mortality excesses recorded at cold and hot temperatures, and minimum at some optimal value, referred as Minimum Mortality Temperature (MMT). As the MMT, which is used to measure the population heat-tolerance, is higher for people living in warmer places, it has been argued that populations will adapt to temperature changes. We tested this notion by taking advantage of a huge migratory flow that occurred in Italy during the 1950s, when a large number of unemployed people moved from the southern to the industrializing north-western regions. We have analyzed mortality–temperature relationships in Milan residen…

Interval estimation for the breakpoint in segmented regression: a smoothed score-based approach

Summary This paper is concerned with interval estimation for the breakpoint parameter in segmented regression. We present score-type confidence intervals derived from the score statistic itself and from the recently proposed gradient statistic. Due to lack of regularity conditions of the score, non-smoothness and non-monotonicity, naive application of the score-based statistics is unfeasible and we propose to exploit the smoothed score obtained via induced smoothing. We compare our proposals with the traditional methods based on the Wald and the likelihood ratio statistics via simulations and an analysis of a real dataset: results show that the smoothed score-like statistics perform in prac…

Respiratory disease phenotypes in a general population sample: latent transition analysis

Background: Few data are available on the temporal pattern of respiratory disease phenotypes in general population. Aim: To detect longitudinal patterns of disease phenotypes related to risk factors and physician visits. Methods: Pisan general population sample from 2 cross-sectional studies (PI1: 1991-93; PI2: 2009-11; n=1107), questionnaire-based data. Latent transition analysis (LTA) was performed to assess respiratory disease phenotypes at PI1 and PI2, labelled according to disease/symptom occurrence. Possible patterns were persistence, worsening and improvement of the phenotype. Multiple logistic regression models were estimated to assess the association among phenotype patterns, risk …

Evidence of bias in randomized clinical trials of hepatitis C interferon therapies

Introduction: Bias may occur in randomized clinical trials in favor of the new experimental treatment because of unblinded assessment of subjective endpoints or wish bias. Using results from published trials, we analyzed and compared the treatment effect of hepatitis C antiviral interferon therapies experimental or control. Methods: Meta-regression of trials enrolling naïve hepatitis C virus patients that underwent four therapies including interferon alone or plus ribavirin during past years. The outcome measure was the sustained response evaluated by transaminases and/or hepatitis C virus-RNA serum load. Data on the outcome across therapies were collected according to the assigned arm (exp…

Reference growth charts for Posidonia oceanica seagrass: An effective tool for assessing growth performance by age and depth

Abstract Growth performance of rhizomes has become among the most used descriptors for monitoring Posidonia oceanica seagrass dynamics and population status. However, ability to detect any change of growth in space or in time is often confounded by natural age-induced decline. To overcome this problem, we have produced reference growth charts, which in other areas are universally recognized as a very powerful tool for comparing growth of living beings during their ontogeny. Reference growth charts involving different P. oceanica growth performance measures (speed of growth and primary production of rhizomes) have been built using proper statistical frameworks (GLMM, Segmented and Quantile R…

Estimating growth charts via nonparametric quantile regression: a practical framework with application in ecology.

We discuss a practical and effective framework to estimate reference growth charts via regression quantiles. Inequality constraints are used to ensure both monotonicity and non-crossing of the estimated quantile curves and penalized splines are employed to model the nonlinear growth patterns with respect to age. A companion R package is presented and relevant code discussed to favour spreading and application of the proposed methods.

Estimating regression models with unknown break-points.

This paper deals with fitting piecewise terms in regression models where one or more break-points are true parameters of the model. For estimation, a simple linearization technique is called for, taking advantage of the linear formulation of the problem. As a result, the method is suitable for any regression model with linear predictor and so current software can be used; threshold modelling as function of explanatory variables is also allowed. Differences between the other procedures available are shown and relative merits discussed. Simulations and two examples are presented to illustrate the method.

Modeling Ordinal Item Responses via Binary GLMMs and Alternative Link Functions: An Application to Measurement of a Perceived Service Quality

Evaluation of a service on the basis of consumer opinion is a widespread practice in many fields. The assessment of perceived quality [7] of a service is generally carried out through administration of a questionnaire, composed of several items with responses posed on an ordinal scale, whereby each item represents an important feature of the evaluated service [3, 7]. In this context, the aim is to evaluate something similar to the external effectiveness, that is the part of efficacy related to the satisfaction expressed by the service users for the provided service. A particular and important example of service users is represented by students’ responses measuring the perceived quality of s…

Upregulation of cytokines and IL-17 in patients with hereditary angioedema

Animal Perception of Seasonal Thresholds: Changes in Elephant Movement in Relation to Rainfall Patterns

Background The identification of temporal thresholds or shifts in animal movement informs ecologists of changes in an animal’s behaviour, which contributes to an understanding of species’ responses in different environments. In African savannas, rainfall, temperature and primary productivity influence the movements of large herbivores and drive changes at different scales. Here, we developed a novel approach to define seasonal shifts in movement behaviour by examining the movements of a highly mobile herbivore (elephant; Loxodonta africana), in relation to local and regional rainfall patterns. Methodology/Principal Findings We used speed to determine movement changes of between 8 and 14 GPS…

Analyzing Temperature Effects on Mortality Within theREnvironment: The Constrained Segmented Distributed Lag Parameterization

Here we present and discuss the R package modTempEff including a set of functions aimed at modelling temperature effects on mortality with time series data. The functions fit a particular log linear model which allows to capture the two main features of mortality- temperature relationships: nonlinearity and distributed lag effect. Penalized splines and segmented regression constitute the core of the modelling framework. We briefly review the model and illustrate the functions throughout a simulated dataset.

Impairment of nasal mucociliary clearance after radiotherapy for childhood head cancer.

Background Radiotherapy of the head region in children is known to cause long-term sequelae, such as facial, dental, and ocular abnormalities. We investigated whether a decreased nasal mucociliary function occurs after radiotherapy of the head in children. Methods A saccharin/charcoal test was performed in 20 children treated with radiotherapy of the head and in 20 controls, age-matched and gender-matched. Results We found a decreased nasal mucociliary clearance (lower percentage of responses (p = 0083) and longer mucociliary transport times (p = .0001) in the patients compared with the controls. The radiotherapy dosage influenced the response to the test (p = .0046). Conclusions Irradiatio…

Testing with a nuisance parameter present only under the alternative: a score-based approach with application to segmented modelling

ABSTRACTWe introduce a score-type statistic to test for a non-zero regression coefficient when the relevant term involves a nuisance parameter present only under the alternative. Despite the non-regularity and complexity of the problem and unlike the previous approaches, the proposed test statistic does not require the nuisance to be estimated. It is simple to implement by relying on the conventional distributions, such as Normal or t, and it justified in the setting of probabilistic coherence. We focus on testing for the existence of a breakpoint in segmented regression, and illustrate the methodology with an analysis on data of DNA copy number aberrations and gene expression profiles from…

A heuristic, iterative algorithm for change-point detection in abrupt change models

Change-point detection in abrupt change models is a very challenging research topic in many fields of both methodological and applied Statistics. Due to strong irregularities, discontinuity and non-smootheness, likelihood based procedures are awkward; for instance, usual optimization methods do not work, and grid search algorithms represent the most used approach for estimation. In this paper a heuristic, iterative algorithm for approximate maximum likelihood estimation is introduced for change-point detection in piecewise constant regression models. The algorithm is based on iterative fitting of simple linear models, and appears to extend easily to more general frameworks, such as models i…

Segmented mixed models with random changepoints: a maximum likelihood approach with application to treatment for depression study

We present a simple and effective iterative procedure to estimate segmented mixed models in a likelihood based framework. Random effects and covariates are allowed for each model parameter, including the changepoint. The method is practical and avoids the computational burdens related to estimation of nonlinear mixed effects models. A conventional linear mixed model with proper covariates that account for the changepoints is the key to our estimating algorithm. We illustrate the method via simulations and using data from a randomized clinical trial focused on change in depressive symptoms over time which characteristically show two separate phases of change.

Subject-specific odds ratios in binomial GLMMs with continuous response

In a regression context, the dichotomization of a continuous outcome variable is often motivated by the need to express results in terms of the odds ratio, as a measure of association between the response and one or more risk factors. Starting from the recent work of Moser and Coombs (Odds ratios for a continuous outcome variable without dichotomizing, Statistics in Medicine, 2004, 23, 1843-1860), in this article we explore in a mixed model framework the possibility of obtaining odds ratio estimates from a regression linear model without the need of dichotomizing the response variable. It is shown that the odds ratio estimators derived from a linear mixed model outperform those from a binom…

Modeling temperature effects on mortality: multiple segmented relationships with common break points.

We present a model for estimation of temperature effects on mortality that is able to capture jointly the typical features of every temperature-death relationship, that is, nonlinearity and delayed effect of cold and heat over a few days. Using a segmented approximation along with a doubly penalized spline-based distributed lag parameterization, estimates and relevant standard errors of the cold- and heat-related risks and the heat tolerance are provided. The model is applied to data from Milano, Italy.

Comment on ‘Estimating average annual per cent change in trend analysis’ by Clegg LX, Hankey BF, Tiwari R, Feuer EJ, Edwards BK, Statistics in Medicine 2009; 28 :3670-3682

Trends in incidence or mortality rates over a specified time interval are usually described by the conventional annual per cent change (cAPC), under the assumption of a constant rate of change. When this assumption does not hold over the entire time interval, the trend may be characterized using the annual per cent changes from segmented analysis (sAPCs). This approach assumes that the change in rates is constant over each time partition defined by the transition points, but varies among different time partitions. Different groups (e.g. racial subgroups), however, may have different transition points and thus different time partitions over which they have constant rates of change, making co…

Exhaled nitric oxide, total serum IgE and allergic sensitization in childhood asthma and allergic rhinitis

Exhaled nitric oxide (eNO) levels are correlated with several markers of atopy and inflammatory activity in the airways, but the relationship between eNO and total serum IgE has not been fully elucidated in the context of allergic sensitization. The aim of this study was to investigate the relationship between eNO, total serum IgE and allergic sensitization in childhood asthma and allergic rhinitis. eNO levels, lung function, skin prick tests and total serum IgE were determined in 109 children (mean age, 10.4 yr) with mild intermittent asthma and in 41 children (mean age, 10.1 yr) with allergic rhinitis; 25 healthy non-atopic children were recruited as controls. eNO levels (median) were sig…