Danilo Alunni Fegatelli

Improved inference on capture recapture models with behavioural effects

In the context of capture-recapture modeling for estimating the unknown size of a finite population it is often required a flexible framework for dealing with a behavioural response to trapping. Many alternative settings have been proposed in the literature to account for the variation of capture probability at each occasion depending on the previous capture history. Inference is typically carried out relying on the so-called conditional likelihood approach. We highlight that such approach may, with positive probability, lead to inferential pathologies such as unbounded estimates for the finite size of the population. The occurrence of such likelihood failures is characterized within a very general class of behavioural effect models. It is also pointed out that a fully Bayesian analysis overcomes the likelihood failure phenomenon. The overall improved performance of alternative Bayesian estimators is investigated under different non-informative prior distributions verifying their comparative merits with both simulated and real data.

A pilot study on the effects of probiotic supplementation on neuropsychological performance and microRNA‐29a‐c levels in antiretroviral‐treated HIV‐1‐infected patients

The gut microbiota is involved in the regulation of cognition, mood, anxiety, and pain, and can impact cognitive functions by producing neuroactive substances or releasing bacterial by‐products and metabolites. No information is available on the effects of a probiotic supplementation on brain function of HIV+ subjects. In light of the above considerations, we performed a pilot study in cART‐treated HIV‐1‐positive patients with long‐term virologic suppression. The aims were to analyze the effect of high‐concentration multistrain probiotic supplementation (Vivomixx®; Visbiome®) on several neurocognitive abilities and to evaluate the safety of this supplementation.

Differential Redox State Contributes to Sex Disparities in the Response to Influenza Virus Infection in Male and Female Mice

Influenza virus replicates intracellularly exploiting several pathways involved in the regulation of host responses. The outcome and the severity of the infection are thus strongly conditioned by multiple host factors, including age, sex, metabolic, and redox conditions of the target cells. Hormones are also important determinants of host immune responses to influenza and are recently proposed in the prophylaxis and treatment. This study shows that female mice are less susceptible than males to mouse-adapted influenza virus (A/PR8/H1N1). Compared with males, PR8-infected females display higher survival rate (+36%), milder clinical disease, and less weight loss. They also have milder histopathological signs, especially free alveolar area is higher than that in males, even if pro-inflammatory cytokine production shows slight differences between sexes; hormone levels, moreover, do not vary significantly with infection in our model. Importantly, viral loads (both in terms of viral M1 RNA copies and tissue culture infectious dose 50%) are lower in PR8-infected females. An analysis of the mechanisms contributing to sex disparities observed during infection reveals that the female animals have higher total antioxidant power in serum and their lungs are characterized by increase in (i) the content and biosynthesis of glutathione, (ii) the expression and activity of antioxidant enzymes (peroxiredoxin 1, catalase, and glutathione peroxidase), and (iii) the expression of the anti-apoptotic protein Bcl-2. By contrast, infected males are characterized by high expression of NADPH oxidase 4 oxidase and phosphorylation of p38 MAPK, both enzymes promoting viral replication. All these factors are critical for cell homeostasis and susceptibility to infection. Reappraisal of the importance of the host cell redox state and sex-related effects may be useful in the attempt to develop more tailored therapeutic interventions in the fight against influenza.

Role of cardiac 123I-mIBG imaging in predicting arrhythmic events in stable chronic heart failure patients with an ICD

BackgroundDespite therapeutic improvement, the prognosis of chronic heart failure (CHF) remains unfavorable partly due to arrhythmia and sudden cardiac death (SCD). This prospective study evaluated myocardial 123I-meta-iodobenzylguanidine (123I-mIBG) scintigraphy as a predictor of arrhythmic events (AE) in CHF patients.Methods170 CHF patients referred for implantable cardioverter-defibrillator (ICD) implantation for both primary and secondary prevention were enrolled. All patients underwent planar and SPECT imaging. Early and late heart-to-mediastinum (H/M) ratio, 123I-mIBG washout (WO), early and late summed SPECT scores were calculated The primary endpoint was an AE: sustained ventricular tachycardia, resuscitated cardiac arrest, appropriate ICD therapy or SCD. The secondary endpoint was appropriate ICD therapy.ResultsDuring a median follow-up of 23.3 months, 69 patients experienced an AE. Early summed score (ESS) was the only independent predictor of AE [HR 1.023 (1.003-1.043)]. Focussing on only patients with an ICD for primary prevention, ESS was the only independent predictor of AE [HR 1.028 (1.007-1.050)]. 123I-mIBG-derived parameters failed to be independent predictors of appropriate ICD therapy. However there was a “bell-shaped” relation between 123I-mIBG scintigraphy-derived parameters and AE and appropriate ICD therapy, i.e., those with intermediate 123I-mIBG abnormalities tended to be at higher risk of events.ConclusionAlthough SPECT 123I-mIBG scintigraphy was associated with AE in CHF patients with ICD implantation for primary and secondary prevention, no association was found between 123I-mIBG scintigraphy-derived parameters and appropriate ICD therapy.

An operational definition of SHATS (Systemic Hemodynamic Atherosclerotic Syndrome): Role of arterial stiffness and blood pressure variability in elderly hypertensive subjects

BACKGROUND CV risk exponentially increases as the number of damaged organs increases The Systemic Hemodynamic Atherosclerotic Syndrome (SHATS) represents a novel conceptualization of the CV continuum focusing on simultaneous multi-organ alteration. This is the first study operationally defining SHATS and aimed at identifying its determinants. METHODS Left Ventricular Hypertrophy (echocardiography), Common Carotid Artery plaque and increased thickness (ultrasound), and Chronic Kidney Disease (estimated Glomerular Filtration Rate) indexed selective target organ damage. SHATS was operationally defined as their simultaneous presence in a patient. PWV was measured by Sphygmocor® and BP variability by 24 h ABPM. RESULTS SHATS affected 19.9% of the 367 studied subjects. Subjects with SHATS had a similar prevalence in diabetes mellitus, but a greater prevalence of very stiff artery (84.9 vs 64.3%, p < 0.01) and use of antihypertensive medications. In the presence of similar office BP, SHATS was associated with higher 24 h SBP and lower 24 h DBP (a greater pulsatile pressure!), reduced nighttime SBP fall, and a twofold greater prevalence of reverse dipper status (48.2 vs 20.2%, p < 0.001). BMI (positive correlation) and DBP (negative correlation) were the only traditional CV risk factors significantly associated with the odds of having SHATS. Very stiff artery and BP variability were significant independent determinants of SHATS, with highly predictive accuracy. CONCLUSION SHATS, the simultaneous damage of multiple target organs, may easily operationally defined. Very stiff artery and BP variability represent key factors for SHATS. The present results support the hypothesis of SHATS as a systemic condition, needing further characterization.

Neurophysiological correlates of bradykinesia in Parkinson’s disease

Many neurophysiological abnormalities have been described in the primary motor cortex of patients with Parkinsons disease. However, it is unclear whether there is any relationship between them and bradykinesia, one of the cardinal motor features of the condition. In the present study we aimed to investigate whether objective measures of bradykinesia in Parkinsons disease have any relationship with neurophysiological measures in primary motor cortex as assessed by means of transcranial magnetic stimulation techniques. Twenty-two patients with Parkinsons disease and 18 healthy subjects were enrolled. Objective measurements of repetitive finger tapping (amplitude, speed and decrement) were obtained using a motion analysis system. The excitability of primary motor cortex was assessed by recording the input/output curve of the motor-evoked potentials and using a conditioning-test paradigm for the assessment of short-interval intracortical inhibition and facilitation. Plasticity-like mechanisms in primary motor cortex were indexed according to the amplitude changes in motor-evoked potentials after the paired associative stimulation protocol. Patients were assessed in two sessions, i.e. OFF and ON medication. A canonical correlation analysis was used to test for relationships between the kinematic and neurophysiological variables. Patients with Parkinsons disease tapped more slowly and with smaller amplitude than normal, and displayed decrement as tapping progressed. They also had steeper input/output curves, reduced short-interval intracortical inhibition and a reduced response to the paired associative stimulation protocol. Within the patient group, bradykinesia features correlated with the slope of the input/output curve and the after-effects of the paired associative stimulation protocol. Although dopaminergic therapy improved movement kinematics as well as neurophysiological measures, there was no relationship between them. In conclusion, neurophysiological changes in primary motor cortex relate to bradykinesia in patients with Parkinsons disease, although other mechanisms sensitive to dopamine levels must also play a role.

The Eutos long-term survival score accurately predicts the risk of death in chronic myeloid leukaemia patients treated outside of clinical trials

gle center study with a small sample of pediatric patients receiving MSDT. Second, MFC based MRD detection does not have a uniform sensitivity across all cases. In summary, our results indicate that for pre-MRD positive cases, haplo-SCT should be chosen, and prophylaxis donor lymphocyte infusion (DLI) should be performed if MSDT is used. Our results, together with the available literature, suggest that monitoring MRD during the peri-transplantation period, in combination with MRD-directed prophylaxis or preemptive therapies, could reduce the incidence of morphologic relapse and improve survival.

Flexible behavioral capture–recapture modeling

We develop alternative strategies for building and fitting parametric capture-recapture models for closed populations which can be used to address a better understanding of behavioral patterns. In the perspective of transition models, we first rely on a conditional probability parameterization. A large subset of standard capture-recapture models can be regarded as a suitable partitioning in equivalence classes of the full set of conditional probability parameters. We exploit a regression approach combined with the use of new suitable summaries of the conditioning binary partial capture histories as a device for enlarging the scope of behavioral models and also exploring the range of all possible partitions. We show how one can easily find unconditional MLE of such models within a generalized linear model framework. We illustrate the potential of our approach with the analysis of some known datasets and a simulation study.

On the design of closed recapture experiments.

We propose a method to plan the number of occasions of recapture experiments for population size estimation. We do so by fixing the smallest number of capture occasions so that the expected length of the profile confidence interval is less than or equal to a fixed threshold. In some cases, we solve the optimization problem in closed form. For more complex models we use numerical optimization. We detail models assuming homogeneous, time-varying, subject-specific capture probabilities, behavioral response to capture, and combining behavioral response with subject-specific effects. The principle we propose can be extended to plan any other model specification. We formally show the validity of the approach by proving distributional convergence. We illustrate with simulations and challenging examples in epidemiology and ecology. We report that in many cases adding as few as two sampling occasions may substantially reduce the length of confidence intervals.

Migraine and attachment type in children and adolescents: what is the role of trauma exposure?

Migraine and attachment insecurity in children and adolescents are often associated. The attachment system can significantly affect the emotional experience and clinical presentation of migraine. The prevalence of migraine in children and adolescent is about 7.7–9.1% and there is a recognized association between migraine and psychiatric comorbidities especially with anxiety disorders, mood disorders, and eating and sleep disorders [1]. Children and adolescents with migraine have an increased risk of developing major depressive episodes and consequently suicide. Furthermore, recent studies reported a significant relationship between migraine and insecure style of attachment. Bowlby defined attachment as a behavioral and cognitive system that regulates an individual’s sense of internal security. According to the most recent studies, traumatic experiences occurring to children with insecure attachment could trigger the activation of the stress mechanism due to the disorganization of the attachment style. Indeed, an increased cortisol secretion triggered by the hypophysis hypothalamus axis adrenal gland (HPA) activation might be responsible for anxiety dysregulation, increased intensity and frequency of headache attacks. Moreover, other researchers found that maltreatments and abuses during childhood increases vulnerability to develop migraine disorder in adulthood. Based on these premises, we have oriented our study on the following objectives: (1) to compare attachment type between children and adolescents with Migraine without Aura (MoA) and a healthy control group; (2) to compare the frequency of trauma exposure in both groups; (3) to examine whether there is a relationship between attachment and trauma impact in both groups; (4) to assess if attachment system or the exposure to trauma affect significantly the clinical presentation of migraine. We investigated these aims through a case-control study. The clinical group was recruited at the BCenter of diagnosis and treatment of Primary Headaches^ of the Department of Pediatrics and Child and Adolescent Neuropsychiatry BSapienza^ University of Rome, Policlinico Umberto I, made up of 101 subjects (55.4% girls; 44.5% boys) aged between 8 and 15 years (mean age 10.84). Children with diagnosis of a secondary headache, presence of diseases that can induce chronic pain, presence of medical or psychiatric comorbidity, patients free of migraine symptomatology for at least 6 months, and patients who stopped the therapy spontaneously were excluded. The control group was recruited in primary and secondary schools of Rome. They were 101 subjects (45.5% girls; 54.4% boys), with mean age of 10.20. The exclusion criteria applied include the following: diagnosis of primary headache or other diagnoses of organic or psychiatric diseases, children younger than age 8 year, and children older than age 15. Headache diagnosis was conducted with the Headache Questionnaire used to investigate the presence or absence of migraine according to the ICHD-3 beta criteria. Perceived attachment security was evaluated using SAT (separation anxiety test), a semiprojective test that allows, in its Italian version, to evaluate the mental models of normal and pathological attachment even in older children (4– 19 years). Finally, the Children’s Impact of Event Scale has been used to measure children and adolescents’ intensity perception of life stress event. With respect to the first objective, our results were in line with most previous studies [2], confirming that children with MoA show higher levels of insecurity attachment than their * Vincenzo Guidetti vincenzo.guidetti@uniroma1.it