Concurrent and predictive validity of the infant motor profile in infants at risk of neurodevelopmental disorders

BACKGROUND: Preterm infants and infants with perinatal brain injury show a higher incidence of neurodevelopmental disorders (NDD). The Infant Motor Profile (IMP) is a clinical assessment which evaluates the complexity of early motor behaviour. More data are needed to confirm its predictive ability and concurrent validity with other common and valid assessments such as the Alberta Infant Motor Scale (AIMS) and Prechtl's General Movement Assessment (GMA). The present study aims to evaluate the concurrent validity of the IMP with the AIMS, to assess its association with the GMA, to evaluate how the IMP reflects the severity of the brain injury and to compare the ability of the IMP and the AIMS to predict an abnormal outcome in 5-month-old infants at risk of NDD.METHODS: 86 infants at risk of NDD were retrospectively recruited among the participants of two clinical trials. Preterm infants with or without perinatal brain injury and term infants with brain injury were assessed at 3months corrected age (CA) using the GMA and at 5months CA using the IMP and the AIMS. The neurodevelopmental outcome was established at 18months.RESULTS: Results confirm a solid concurrent validity between the IMP Total Score and the AIMS (Spearman's rho 0.76; p<.001) and a significant association between IMP Total Score and the GMA. Unlike the AIMS, the IMP Total score accurately reflects the severity of neonatal brain injury (p<.001) and proves to be the strongest predictor of NDD (p<.001). The comparison of areas under receiver operating characteristic curves (AUC) confirms that the IMP Total score has the highest diagnostic accuracy at 5months (AUC 0.92). For an optimal IMP Total Score cut-off value of 70, the assessment shows high sensitivity (93%) and specificity (81%) (PPV 84%; NPV 90%).CONCLUSIONS: Early motor behaviour assessed with the IMP is strongly associated with middle-term neurodevelopmental outcome. The present study confirms the concurrent validity of the IMP with the AIMS, its association with the GMA and its ability to reflect brain lesion load, hence contributing to the construct validity of the assessment.TRIAL REGISTRATION: NCT01990183 and NCT03234959 (clinicaltrials.gov)

Machine Learning of Atomic Dynamics and Statistical Surface Identities in Gold Nanoparticles

It is known that metal nanoparticles (NPs) may be dynamic and atoms may move within them even at fairly low temperatures. Characterizing such complex dynamics is key for understanding NPs’ properties in realistic regimes, but detailed information on, e.g., the stability, survival, and interconversion rates of the atomic environments (AEs) populating them are non-trivial to attain. Here we show a machine learning approach that allows us to reconstruct the complex atomic dynamics of metal NPs from high-dimensional data extracted from molecular dynamics simulations. Using different-shape gold NPs as a representative example, an AEs’ dictionary allows us to label step-by-step the individual atoms in the NPs, identifying the native and non-native AEs and populating them along the MD simulations at various temperatures. Tracking the emergence, annihilation, lifetime, and dynamic interconversion of the AEs, our approach permits estimating a “statistical equivalent identity” for metal NPs based on the intrinsic atomic dynamics present within them

Early intervention at home in infants with congenital brain lesion with CareToy revised: a RCT protocol

Abstract Background Congenital brain lesions expose infants to be at high-risk for being affected by neurodevelopmental disorders such as cerebral palsy (CP). Early interventions programs can significantly impact and improve their neurodevelopment. Recently, in the framework of the European CareToy (CT) Project (www.caretoy.eu), a new medical device has been created to deliver an early, intensive, customized, intervention program, carried out at home by parents but remotely managed by expert and trained clinicians. Reviewing results of previous studies on preterm infants without congenital brain lesion, the CT platform has been revised and a new system created (CT-R). This study describes the protocol of a randomised controlled trial (RCT) aimed to evaluate, in a sample of infants at high-risk for CP, the efficacy of CT-R intervention compared to the Infant Massage (IM) intervention. Methods/design This RCT will be multi-centre, paired and evaluator-blinded. Eligible subjects will be preterm or full-term infants with brain lesions, in first year of age with predefined specific gross motor abilities. Recruited infants will be randomized into CT-R and IM groups at baseline (T0). Based on allocation, infants will perform an 8-week programme of personalized CareToy activities or Infant Massage. The primary outcome measure will be the Infant Motor Profile. On the basis of power calculation, it will require a sample size of 42 infants. Moreover, Peabody Developmental Motor Scales-Second Edition, Teller Acuity Cards, standardized video-recordings of parent-infant interaction and wearable sensors (Actigraphs) will be included as secondary outcome measures. Finally, parents will fill out questionnaires (Bayley Social-Emotional, Parents Stress Index). All outcome measures will be carried out at the beginning (T0) and at end of 8-weeks intervention period, primary endpoint (T1). Primary outcome and some secondary outcomes will be carried out also after 2 months from T1 and at 18 months of age (T2 and T3, respectively). The Bayley Cognitive subscale will be used as additional assessment at T3. Discussion This study protocol paper is the first study aimed to test CT-R system in infants at high-risk for CP. This paper will present the scientific background and trial methodology. Trial registration NCT03211533 and NCT03234959 (www.clinicaltrials.gov)

Machine learning of atomic dynamics and statistical surface identities in gold nanoparticles

Abstract It is known that metal nanoparticles (NPs) may be dynamic and atoms may move within them even at fairly low temperatures. Characterizing such complex dynamics is key for understanding NPs’ properties in realistic regimes, but detailed information on, e.g., the stability, survival, and interconversion rates of the atomic environments (AEs) populating them are non-trivial to attain. In this study, we decode the intricate atomic dynamics of metal NPs by using a machine learning approach analyzing high-dimensional data obtained from molecular dynamics simulations. Using different-shape gold NPs as a representative example, an AEs’ dictionary allows us to label step-by-step the individual atoms in the NPs, identifying the native and non-native AEs and populating them along the MD simulations at various temperatures. By tracking the emergence, annihilation, lifetime, and dynamic interconversion of the AEs, our approach permits estimating a “statistical equivalent identity” for metal NPs, providing a comprehensive picture of the intrinsic atomic dynamics that shape their properties

Binding Free Energies of Host–Guest Systems by Nonequilibrium Alchemical Simulations with Constrained Dynamics: Illustrative Calculations and Numerical Validation

In the companion article (Giovannelli et al., 10.1021/acs.jctc.7b00594), we presented an alchemical approach, based on nonequilibrium molecular dynamics simulations, to compute absolute binding free energies of a generic host–guest system. Two alternative computational routes, called binded-domain and single-point alchemical-path schemes, have been proposed. This study is addressed to furnish numerical validation and illustrative examples of the above-mentioned alchemical schemes. Validation is provided by comparing binding free-energy data relative to two poses of a Zn­(II)·anion complex with those recovered from an alternative approach, based on steered molecular dynamics simulations. We illustrate important technical and theoretical aspects for a good practice in applying both alchemical schemes, not only through the calculations on the Zn­(II)·anion complex, but also estimating absolute binding free energies of 1:1 complexes of β-cyclodextrin with aromatic compounds (benzene and naphthalene). Comparison with experimental data and previous molecular dynamics simulation studies further confirms the validity of the present nonequilibrium-alchemical methodology

Early intervention at home in infants with congenital brain lesion with CareToy revised: A RCT protocol

Background: Congenital brain lesions expose infants to be at high-risk for being affected by neurodevelopmental disorders such as cerebral palsy (CP). Early interventions programs can significantly impact and improve their neurodevelopment. Recently, in the framework of the European CareToy (CT) Project ( www.caretoy.eu ), a new medical device has been created to deliver an early, intensive, customized, intervention program, carried out at home by parents but remotely managed by expert and trained clinicians. Reviewing results of previous studies on preterm infants without congenital brain lesion, the CT platform has been revised and a new system created (CT-R). This study describes the protocol of a randomised controlled trial (RCT) aimed to evaluate, in a sample of infants at high-risk for CP, the efficacy of CT-R intervention compared to the Infant Massage (IM) intervention. Methods/design: This RCT will be multi-centre, paired and evaluator-blinded. Eligible subjects will be preterm or full-term infants with brain lesions, in first year of age with predefined specific gross motor abilities. Recruited infants will be randomized into CT-R and IM groups at baseline (T0). Based on allocation, infants will perform an 8-week programme of personalized CareToy activities or Infant Massage. The primary outcome measure will be the Infant Motor Profile. On the basis of power calculation, it will require a sample size of 42 infants. Moreover, Peabody Developmental Motor Scales-Second Edition, Teller Acuity Cards, standardized video-recordings of parent-infant interaction and wearable sensors (Actigraphs) will be included as secondary outcome measures. Finally, parents will fill out questionnaires (Bayley Social-Emotional, Parents Stress Index). All outcome measures will be carried out at the beginning (T0) and at end of 8-weeks intervention period, primary endpoint (T1). Primary outcome and some secondary outcomes will be carried out also after 2 months from T1 and at 18 months of age (T2 and T3, respectively). The Bayley Cognitive subscale will be used as additional assessment at T3. Discussion: This study protocol paper is the first study aimed to test CT-R system in infants at high-risk for CP. This paper will present the scientific background and trial methodology

ERICA (Stopping Child Maltreatment through Pan-European Multiprofessional Training Programme: Early Child Protection Work with Families at Risk) Training Programme Design

This paper describes the design and development of the ERICA (Stopping Child Maltreatment through a Pan European Multiprofessional Training Programme: Early Child Protection Work with Families at Risk) training programme. ERICA project was funded by the Rights, Equality and Citizenship Funding programme of the European Commission (European Commission 2019-2021), and has an overarching aim to develop, pilot and evaluate a Europe wide training programme in prevention, assessment, support and referral in relation to child maltreatment. It is a pan-European partnership with collaborators from Finland, England, Scotland, France, Germany, Italy and Poland. ERICA project proposes an integrated strategy to deal with child maltreatment risk and child maltreatment that consists of a multidisciplinary training across services and professional profiles, plus the design and promotion of a community engagement strategy, to build protective factors around families at risk and families suffering from child maltreatment

Tolerability of vortioxetine compared to selective serotonin reuptake inhibitors in older adults with major depressive disorder (VESPA): a randomised, assessor-blinded and statistician-blinded, multicentre, superiority trialResearch in context

Summary: Background: Major depressive disorder (MDD) is prevalent and disabling among older adults. Standing on its tolerability profile, vortioxetine might be a promising alternative to selective serotonin reuptake inhibitors (SSRIs) in such a vulnerable population. Methods: We conducted a randomised, assessor- and statistician-blinded, superiority trial including older adults with MDD. The study was conducted between 02/02/2019 and 02/22/2023 in 11 Italian Psychiatric Services. Participants were randomised to vortioxetine or one of the SSRIs, selected according to common practice. Treatment discontinuation due to adverse events after six months was the primary outcome, for which we aimed to detect a 12% difference in favour of vortioxetine. The study was registered in the online repository clinicaltrials.gov (NCT03779789). Findings: The intention-to-treat population included 179 individuals randomised to vortioxetine and 178 to SSRIs. Mean age was 73.7 years (standard deviation 6.1), and 264 participants (69%) were female. Of those on vortioxetine, 78 (44%) discontinued the treatment due to adverse events at six months, compared to 59 (33%) of those on SSRIs (odds ratio 1.56; 95% confidence interval 1.01–2.39). Adjusted and per-protocol analyses confirmed point estimates in favour of SSRIs, but without a significant difference. With the exception of the unadjusted survival analysis showing SSRIs to outperform vortioxetine, secondary outcomes provided results consistent with a lack of substantial safety and tolerability differences between the two arms. Overall, no significant differences emerged in terms of response rates, depressive symptoms and quality of life, while SSRIs outperformed vortioxetine in terms of cognitive performance. Interpretation: As opposed to what was previously hypothesised, vortioxetine did not show a better tolerability profile compared to SSRIs in older adults with MDD in this study. Additionally, hypothetical advantages of vortioxetine on depression-related cognitive symptoms might be questioned. The study's statistical power and highly pragmatic design allow for generalisability to real-world practice. Funding: The study was funded by the Italian Medicines Agency within the “2016 Call for Independent Drug Research”