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Abstract Human brain morphology undergoes complex changes over the lifespan. Despite recent progress in tracking brain development via normative models, current knowledge of underlying biological mechanisms is highly limited. We demonstrate that human cortical thickness development and aging trajectories unfold along patterns of molecular and cellular brain organization, traceable from population-level to individual developmental trajectories. During childhood and adolescence, cortex-wide spatial distributions of dopaminergic receptors, inhibitory neurons, glial cell populations, and brain-metabolic features explain up to 50% of the variance associated with a lifespan model of regional cortical thickness trajectories. In contrast, modeled cortical thickness change patterns during adulthood are best explained by cholinergic and glutamatergic neurotransmitter receptor and transporter distributions. These relationships are supported by developmental gene expression trajectories and translate to individual longitudinal data from over 8000 adolescents, explaining up to 59% of developmental change at cohort- and 18% at single-subject level. Integrating neurobiological brain atlases with normative modeling and population neuroimaging provides a biologically meaningful path to understand brain development and aging in living humans.

Introduction:A growing literature has shown that exposure to adverse life events during childhood or adolescence is associated with the presence of psychotic-like experiences (PLEs), which is in turn associated with the risk of psychotic outcomes. Ruminative thinking, i.e., the tendency to dwell on particular issues or ideas, may affect the perceived aversiveness and ability to cope with adverse life events. However, the role that rumination plays in the relationship between adverse life events and the presence of PLEs remains unclear. The purpose of this study is to assess the association between adverse life events and PLEs in a longitudinal sample of young adults and adolescents, and to investigate whether this relationship is mediated by ruminative thinking.MethodsWe used a longitudinal naturalistic sample of 706 volunteers assessed at ages 18 and 22 years, within the Imagen consortium. Lifetime occurrence of adverse life events (i.e., events perceived as strongly negative by participants) was investigated using the Life Events Questionnaire. The Community Assessment of Psychic Experience (CAPE-42) served to assess the presence of PLEs, while ruminative thinking was investigated through the Ruminative Response Scale.ResultsResults showed that both frequency of PLEs and their persistence over time were associated with greater adverse life events exposure (r = 0.32, p < 0.001 and F1 = 9.8; p < 0.001, respectively) and greater ruminative response (r = 0.66, p < 0.001 and F1 = 94.9; p < 0.001, respectively). Mediation analyses showed that relationship between adverse life events and PLEs frequency was partially mediated by rumination (direct effect Z: 5.4, p < 0.001; indirect effect Z: 6.9, p < 0.001; total effect Z: 5.9, p < 0.001). Considering changes between the two assessment timepoints, relationship between PLEs variation between 18 and 22 years and adverse life events occurred during the same period was partially mediated by changes in rumination (direct effect Z: 2.8, p < 0.005; indirect effect Z: 4.3, p < 0.001; total effect Z: 4.3; p < 0.001).DiscussionOverall, our findings confirm that the presence of adverse life events may increase the risk of experiencing PLEs in healthy individuals and suggest that dysfunctional coping strategies, such as ruminative thinking, may be related to psychosis proneness. Results do not disentangle whether individuals with greater risk for psychosis tend to ruminate more or whether rumination exacerbates psychosis risk.

Abstract Adolescents exhibit remarkable heterogeneity in the structural architecture of brain development. However, due to limited large-scale longitudinal neuroimaging studies, existing research has largely focused on population averages, and the neurobiological basis underlying individual heterogeneity remains poorly understood. Here we identify, using the IMAGEN adolescent cohort followed up over 9 years (14–23 y), three groups of adolescents characterized by distinct developmental patterns of whole-brain gray matter volume (GMV). Group 1 show continuously decreasing GMV associated with higher neurocognitive performances than the other two groups during adolescence. Group 2 exhibit a slower rate of GMV decrease and lower neurocognitive performances compared with Group 1, which was associated with epigenetic differences and greater environmental burden. Group 3 show increasing GMV and lower baseline neurocognitive performances due to a genetic variation. Using the UK Biobank, we show these differences may be attenuated in mid-to-late adulthood. Our study reveals clusters of adolescent neurodevelopment based on GMV and the potential long-term impact.

Adolescence is a crucial period for physical and psychological development. The impact of negative life events represents a risk factor for the onset of neuropsychiatric disorders. This study aims to investigate the relationship between negative life events and structural brain connectivity, considering both graph theory and connectivity strength. A group (n = 487) of adolescents from the IMAGEN Consortium was divided into Low and High Stress groups. Brain networks were extracted at an individual level, based on morphological similarity between grey matter regions with regions defined using an atlas-based region of interest (ROI) approach. Between-group comparisons were performed with global and local graph theory measures in a range of sparsity levels. The analysis was also performed in a larger sample of adolescents (n = 976) to examine linear correlations between stress level and network measures. Connectivity strength differences were investigated with network-based statistics. Negative life events were not found to be a factor influencing global network measures at any sparsity level. At local network level, between-group differences were found in centrality measures of the left somato-motor network (a decrease of betweenness centrality was seen at sparsity 5%), of the bilateral central visual and the left dorsal attention network (increase of degree at sparsity 10% at sparsity 30% respectively). Network-based statistics analysis showed an increase in connectivity strength in the High stress group in edges connecting the dorsal attention, limbic and salience networks. This study suggests negative life events alone do not alter structural connectivity globally, but they are associated to connectivity properties in areas involved in emotion and attention.

Background: Bone loss resulting from high energy trauma, infections or resection after tumours is certainly a challenge. In this case, not only did the patient suffer from high energy trauma but also chronic osteomyelitis was present, which made the management even more challenging. Case report: A 29-year-old woman was admitted to the emergency department due to complains of pain and leakage on her right upper lower limb. The treatment plan consisted of three large operations to eliminate osteomyelitis and to achieve bone transport with the use of an intramedullary magnetic nail. Conclusion: The combination of bone loss and osteomyelitis is an issue that requires long-term therapeutic interventions and determination from the patient. The use of an intramedullary magnetic nail for bone transport is a pioneer method with limited literature, but with sufficient results.

Objectives To assess the effect of adjuvant antibiotic-loaded hydrogel application on the primary stability of implanted uncemented hip stems.Design Biomechanical study.Setting An electro-mechanic material test system (#5866, Instron, Norwood, MA, USA) equipped with a 10-kN load cell was used. A staircase loading protocol was applied via quasi-static ramped compression loading at 0.005 mm/s and six different load levels between 500 N and 3000 N in 500 N intermittent load increase steps.Participants 12 artificial femora were prepared and received a collarless uncemented standard offset stem (Corail; DePuy Synthes, Zuchwil, Switzerland).Interventions The two groups were prepared with or without the antibiotic-loaded hydrogel.Main outcome measures Construct stiffness was determined from the recorded load-displacement curves and stem subsidence was measured via motion tracking.Results Construct stiffness (control: 4176±240 N/mm; intervention: 4588±448 N/mm) was not significantly different between the groups (p=0.076). Stem subsidence increased significantly over the increasing load levels in each separate group (p≤0.002) and remained not significantly different between the groups (p=0.609).Conclusions The application of antibiotic-loaded hydrogel was associated with non-inferior performance in terms of primary uncemented hip stem stability. This finding makes the prospect of adjuvant antibiotic-loaded hydrogel application potentially feasible; however, it requires further investigations prior to translation in the clinical practice.

Structural brain aging has demonstrated strong inter-individual heterogeneity and mirroring patterns with brain development. However, due to the lack of large-scale longitudinal neuroimaging studies, most of the existing research focused on the cross-sectional changes of brain aging. In this investigation, we present a data-driven approach that incorporate both cross-sectional changes and longitudinal trajectories of structural brain aging and identified two brain aging patterns among 37,013 healthy participants from UK Biobank. Participants with accelerated brain aging also demonstrated accelerated biological aging, cognitive decline and increased genetic susceptibilities to major neuropsychiatric disorders. Further, by integrating longitudinal neuroimaging studies from a multi-center adolescent cohort, we validated the ‘last in, first out’ mirroring hypothesis and identified brain regions with manifested mirroring patterns between brain aging and brain development. Genomic analyses revealed risk loci and genes contributing to accelerated brain aging and delayed brain development, providing molecular basis for elucidating the biological mechanisms underlying brain aging and related disorders.

Substance use, including cigarettes and cannabis, is associated with poorer sustained attention in late adolescence and early adulthood. Previous studies were predominantly cross-sectional or under-powered and could not indicate if impairment in sustained attention was a predictor of substance use or a marker of the inclination to engage in such behavior. This study explored the relationship between sustained attention and substance use across a longitudinal span from ages 14 to 23 in over 1000 participants. Behaviors and brain connectivity associated with diminished sustained attention at age 14 predicted subsequent increases in cannabis and cigarette smoking, establishing sustained attention as a robust biomarker for vulnerability to substance use. Individual differences in network strength relevant to sustained attention were preserved across developmental stages and sustained attention networks generalized to participants in an external dataset. In summary, brain networks of sustained attention are robust, consistent, and able to predict aspects of later substance use.

Abstract Background Preterm birth is a major health issue due to its potential outcomes and socioeconomic impact. Prenatal counseling is of major importance for parents because it is believed that the risk of preterm birth is associated with a higher parental mental burden. Nowadays in France, the content and delivery of antenatal counseling is based on personal experience since there is a lack of official guidelines. The goal of the study was to evaluate maternal perception of antenatal information delivered in the setting of preterm births. Methods A qualitative study was performed using semi-structured individual interviews of 15 mothers with a child born > 26–34 GW. Data analysis was based on a constant comparative method. Results Concerning prenatal counseling content, parents wanted to be informed of their role in the care of their preterm child more so than statistics that were not always considered relevant. Parents’ reactions to the announcement of the risk of a preterm birth was dominated by stupefaction, uncertainty and anxiety. When it comes to the setting of prenatal counseling, patients’ room was deemed an appropriate setting by parents and ideally the presence of a coparent was appreciated as it increased patients’ understanding. The physicians’ attitude during the counseling was considered appropriate and described as empathic and optimistic. The importance of support throughout the hospitalization in the form of other parents’ experiences, healthcare professionals and the possibility to preemptively visit the NICU was emphasized by participants. Delivery experience was dominated by a sense of uncertainty, and urgency. Some leads for improvement included additional support of information such as virtual NICU visit; participants also insisted on continuity of care and the multidisciplinary aspect of counseling (obstetrician, neonatologist, midwife, nurse, lactation consultant and psychologist). Conclusion Highlighting parents’ expectations about prenatal counseling could lead to the establishment of overall general guidelines. However, some topics like the use of statistics and mentioning the risk of death underline the importance of a personalized information.

This study explored the generality versus specificity of two trait-liability factors for externalizing problems-disinhibition and callousness-in the concurrent and prospective prediction of symptoms of conduct disorder, attention-deficit/hyperactivity disorder (ADHD), and substance use (i.e., alcohol use disorder and history of illicit substance use). Disinhibition involves an impulsive, unrestrained cognitive-behavioral style; callousness entails a dispositional lack of social-emotional sensitivity. Participants were European adolescents from the multisite IMAGEN project who completed questionnaires and clinical interviews at ages 14 (N = 1,504, Mage = 14.41, 51.13% female) and 16 (N = 1,407, Mage = 16.46, 51.88% female). Disinhibition was related concurrently and prospectively to greater symptoms of conduct disorder, ADHD, and alcohol use disorder; higher scores on a general externalizing factor; and greater likelihood of having tried an illicit substance. Callousness was selectively related to greater conduct disorder symptoms. These findings indicate disinhibition confers broad liability for externalizing spectrum disorders, perhaps due to its affiliated deficits in executive function. In contrast, callousness appears to represent more specific liability for antagonistic (aggressive/exploitative) forms of externalizing, as exemplified by antisocial behavior. Results support the utility of developmental-ontogenetic and hierarchical-dimensional models of psychopathology and have important implications for early assessment of risk for externalizing problems. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

According to European regulation 2023/1804/EU, all member states shall ensure the availability of cold ironing (CI) in large ports for at least 90 % of the total number of port calls of seagoing ships above 5000 gross tonnes, by the end of 2029. This is a measure expected to improve air quality, especially in the vicinity of the port's urban environment. Preliminary studies show that there are financial viability issues related to CI installations, under the current electricity pricing policies and the high investment cost for CI infrastructure. In this paper, the financial viability of the penetration of photovoltaic (PV) units optimized from spatial and power produced point of view is investigated. The proposed method is applied to various ship types, indicatively for the Thessaloniki Port, taking into consideration the connection with the Medium Voltage (MV) electricity distribution grid, as well as the construction, operation, and maintenance costs, under modified economic criterion of benefit-cost ratio (BCR).

BackgroundManagement of young febrile infants is challenging. Therefore, several guidelines have been developed over the last decades. However, knowledge regarding the impact of introducing guidelines for febrile infants is limited. We assessed the impact of and adherence to a novel guideline for managing febrile infants aged ≤59 days.MethodsThis retrospective cross-sectional study was conducted in 2 pediatric emergency departments in Sweden between 2014 and 2021. We compared the management of infants aged ≤59 days with fever without a source (FWS) and the diagnosis of serious bacterial infections (SBIs) before and after implementing the new guideline.ResultsWe included 1,326 infants aged ≤59 days with FWS. Among infants aged ≤21 days, urine cultures increased from 49% to 67% (p = 0.001), blood cultures from 43% to 63% (p

Abstract Background The complement system is an important arm of immune defense bringing innate and adaptive immunity. Although originally regarded as a major complementary defense mechanism against pathogens, continuously emerging evidence has uncovered a central role of this complex system in several diseases including lung pathologies. Main body Complement factors such as anaphylatoxins C3a and C5a, their receptors C3aR, C5aR and C5aR2 as well as complement inhibitory proteins CD55, CD46 and CD59 have been implicated in pathologies such as the acute respiratory distress syndrome, pneumonia, chronic obstructive pulmonary disease, asthma, interstitial lung diseases, and lung cancer. However, the exact mechanisms by which complement factors induce these diseases remain unclear. Several complement-targeting monoclonal antibodies are reported to treat lung diseases. Conclusions The complement system contributes to the progression of the acute and chronic lung diseases. Better understanding of the underlying mechanisms will provide groundwork to develop new strategy to target complement factors for treatment of lung diseases.

Abstract Background The management of febrile infants aged ≤ 60 days and adherence to guidelines vary greatly. Our objective was to describe the process of decision-making when managing febrile infants aged ≤ 60 days and to describe the factors that influenced this decision. Methods We conducted 6 focus group discussions with 19 clinically active physicians in the pediatric emergency departments of 2 university hospitals in Skåne region, Sweden. We followed an inductive qualitative design, using a phenomenological approach. A second-order perspective was used, focusing on how physicians perceived the phenomenon (managing fever in infants) rather than the phenomenon itself. The transcribed interviews were analyzed using a 7-step approach. Results Performing a lumbar puncture (LP) was conceived as a complex, emotionally and mentally laden procedure and dominated the group discussions. Three central categories emerged as factors that influenced the decision-making process on whether to perform an LP: 1) a possible focus of infection that could explain the origin of the fever, 2) questioning whether the temperature at home reported by the parents was a fever, especially if it was ≤ 38.2°C, and 3) the infant’s general condition and questioning the need for LP in case of well-appearing infants. Around these 3 central categories evolved 6 secondary categories that influenced the decision-making process of whether to perform an LP or not: 1) the physicians’ desire to be able to trust their judgement, 2) fearing the risk of failure, 3) avoiding burdensome work, 4) taking others into account, 5) balancing guidelines and resources, and 6) seeing a need to practice and learn to perform LP. Conclusions The difficulty and emotional load of performing an LP were important factors that influenced the decision-making process regarding whether to perform an LP. Physicians highlighted the importance of being able to rely on their clinical judgment and make independent decisions. Guidelines may consider allowing a degree of flexibility and independent thinking to take into account patients’ characteristics and needs.

Aims: We aim to evaluate the usefulness of postoperative blood tests by investigating the incidence of abnormal results following total joint replacement (TJR), as well as identifying preoperative risk factors for abnormal blood test results postoperatively, especially pertaining to anaemia and acute kidney injury (AKI). Methods: This is a retrospective cohort study of patients who had elective TJR between January and December 2019 at a tertiary centre. Data gathered included age at time of surgery, sex, BMI, American Society of Anesthesiologists (ASA) grade, preoperative and postoperative laboratory test results, haemoglobin (Hgb), white blood count (WBC), haematocrit (Hct), platelets (Plts), sodium (Na+), potassium (K+), creatinine (Cr), estimated glomerular filtration rate (eGFR), and Ferritin (ug/l). Abnormal blood tests, AKI, electrolyte imbalance, anaemia, transfusion, reoperation, and readmission within one year were reported. Results: The study included 2,721 patients with a mean age of 69 years, of whom 1,266 (46.6%) were male. Abnormal postoperative bloods were identified in 444 (16.3%) patients. We identified age (≥ 65 years), female sex, and ASA grade ≥ III as risk factors for developing abnormal postoperative blood tests. Preoperative haemoglobin (≤ 127 g/dl) and packed cell volume (≤ 0.395 l/l) were noted to be significant risk factors for postoperative anaemia, and potassium (≤ 3.7 mmol/l) was noted to be a significant risk factor for AKI. Conclusion: The costs outweigh the benefits of ordering routine postoperative blood tests in TJR patients. Clinicians should risk-stratify their patients and have a lower threshold for ordering blood tests in patients with abnormal preoperative haemoglobin (≤ 127 g/l), blood loss > 300 ml, chronic kidney disease, ASA grade ≥ III, and clinical concern. Cite this article: Bone Jt Open 2023;4(11):899–905.

Despite numerous therapeutic advances in pulmonary arterial hypertension, patients continue to suffer high morbidity and mortality, particularly considering a median age of 50 years. This article explores whether early, robust reduction of right ventricular afterload would facilitate substantial improvement in right ventricular function and thus whether afterload reduction should be a treatment goal for pulmonary arterial hypertension. The earliest clinical studies of prostanoid treatment in pulmonary arterial hypertension demonstrated an important link between lowering mean pulmonary arterial pressure (or pulmonary vascular resistance) and improved survival. Subsequent studies of oral monotherapy or sequential combination therapy demonstrated smaller reductions in mean pulmonary arterial pressure and pulmonary vascular resistance. More recently, retrospective reports of initial aggressive prostanoid treatment or initial combination oral and parenteral therapy have shown marked afterload reduction along with significant improvements in right ventricular function. Some data suggest that reaching threshold levels for pressure or resistance (components of right ventricular afterload) may be key to interrupting the self-perpetuating injury of pulmonary vascular disease in pulmonary arterial hypertension and could translate into improved long-term clinical outcomes. Based on these clues, the authors postulate that improved clinical outcomes might be achieved by targeting significant afterload reduction with initial oral combination therapy and early parenteral prostanoids.

Abstract Smoking of cigarettes among young adolescents is a pressing public health issue. However, the neural mechanisms underlying smoking initiation and sustenance during adolescence, especially the potential causal interactions between altered brain development and smoking behaviour, remain elusive. Here, using large longitudinal adolescence imaging genetic cohorts, we identify associations between left ventromedial prefrontal cortex (vmPFC) gray matter volume (GMV) and subsequent self-reported smoking initiation, and between right vmPFC GMV and the maintenance of smoking behaviour. Rule-breaking behaviour mediates the association between smaller left vmPFC GMV and smoking behaviour based on longitudinal cross-lagged analysis and Mendelian randomisation. In contrast, smoking behaviour associated longitudinal covariation of right vmPFC GMV and sensation seeking (especially hedonic experience) highlights a potential reward-based mechanism for sustaining addictive behaviour. Taken together, our findings reveal vmPFC GMV as a possible biomarker for the early stages of nicotine addiction, with implications for its prevention and treatment.

Abstract Background Early negative life events (NLE) have long‐lasting influences on neurodevelopment and psychopathology. Reduced orbitofrontal cortex (OFC) thickness was frequently associated with NLE and depressive symptoms. OFC thinning might mediate the effect of NLE on depressive symptoms, although few longitudinal studies exist. Using a complete longitudinal design with four time points, we examined whether NLE during childhood and early adolescence predict depressive symptoms in young adulthood through accelerated OFC thinning across adolescence. Methods We acquired structural MRI from 321 participants at two sites across four time points from ages 14 to 22. We measured NLE with the Life Events Questionnaire at the first time point and depressive symptoms with the Center for Epidemiologic Studies Depression Scale at the fourth time point. Modeling latent growth curves, we tested whether OFC thinning mediates the effect of NLE on depressive symptoms. Results A higher burden of NLE, a thicker OFC at the age of 14, and an accelerated OFC thinning across adolescence predicted young adults' depressive symptoms. We did not identify an effect of NLE on OFC thickness nor OFC thickness mediating effects of NLE on depressive symptoms. Conclusions Using a complete longitudinal design with four waves, we show that NLE in childhood and early adolescence predict depressive symptoms in the long term. Results indicate that an accelerated OFC thinning may precede depressive symptoms. Assessment of early additionally to acute NLEs and neurodevelopment may be warranted in clinical settings to identify risk factors for depression.

Summary: During late adolescence, the brain undergoes ontogenic organization altering subcortical-cortical circuitry. This includes regions implicated in pain chronicity, and thus alterations in the adolescent ontogenic organization could predispose to pain chronicity in adulthood - however, evidence is lacking. Using resting-state functional magnetic resonance imaging from a large European longitudinal adolescent cohort and an adult cohort with and without chronic pain, we examined links between painful symptoms and brain connectivity. During late adolescence, thalamo-, caudate-, and red nucleus-cortical connectivity were positively and subthalamo-cortical connectivity negatively associated with painful symptoms. Thalamo-cortical connectivity, but also subthalamo-cortical connectivity, was increased in adults with chronic pain compared to healthy controls. Our results indicate a shared basis in basothalamo-cortical circuitries between adolescent painful symptomatology and adult pain chronicity, with the subthalamic pathway being differentially involved, potentially due to a hyperconnected thalamo-cortical pathway in chronic pain and ontogeny-driven organization. This can inform neuromodulation-based prevention and early intervention.

BackgroundDysfunctional reward processing is implicated in multiple mental disorders. Novelty seeking (NS) assesses preference for seeking novel experiences, which is linked to sensitivity to reward environmental cues.MethodsA subset of 14-year-old adolescents (IMAGEN) with the top 20% ranked high-NS scores was used to identify high-NS-associated multimodal components by supervised fusion. These features were then used to longitudinally predict five different risk scales for the same and unseen subjects (an independent dataset of subjects at 19 years of age that was not used in predictive modeling training at 14 years of age) (within IMAGEN, n ≈1100) and even for the corresponding symptom scores of five types of patient cohorts (non-IMAGEN), including drinking (n = 313), smoking (n = 104), attention-deficit/hyperactivity disorder (n = 320), major depressive disorder (n = 81), and schizophrenia (n = 147), as well as to classify different patient groups with diagnostic labels.ResultsMultimodal biomarkers, including the prefrontal cortex, striatum, amygdala, and hippocampus, associated with high NS in 14-year-old adolescents were identified. The prediction models built on these features are able to longitudinally predict five different risk scales, including alcohol drinking, smoking, hyperactivity, depression, and psychosis for the same and unseen 19-year-old adolescents and even predict the corresponding symptom scores of five types of patient cohorts. Furthermore, the identified reward-related multimodal features can classify among attention-deficit/hyperactivity disorder, major depressive disorder, and schizophrenia with an accuracy of 87.2%.ConclusionsAdolescents with higher NS scores can be used to reveal brain alterations in the reward-related system, implicating potential higher risk for subsequent development of multiple disorders. The identified high-NS-associated multimodal reward-related signatures may serve as a transdiagnostic neuroimaging biomarker to predict disease risks or severity.

DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)-three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.

Abstract Background This paper discusses whether baseline demographic, socio-economic, health variables, length of follow-up and method of contacting the participants predict non-response to the invitation for a second assessment of lifestyle factors and body weight in the European multi-center EPIC-PANACEA study. Methods Over 500.000 participants from several centers in ten European countries recruited between 1992 and 2000 were contacted 2–11 years later to update data on lifestyle and body weight. Length of follow-up as well as the method of approaching differed between the collaborating study centers. Non-responders were compared with responders using multivariate logistic regression analyses. Results Overall response for the second assessment was high (81.6%). Compared to postal surveys, centers where the participants completed the questionnaire by phone attained a higher response. Response was also high in centers with a short follow-up period. Non-response was higher in participants who were male (odds ratio 1.09 (confidence interval 1.07; 1.11), aged under 40 years (1.96 (1.90; 2.02), living alone (1.40 (1.37; 1.43), less educated (1.35 (1.12; 1.19), of poorer health (1.33 (1.27; 1.39), reporting an unhealthy lifestyle and who had either a low (25, 1.08 (1.06; 1.10); especially ≥30 kg/m2, 1.26 (1.23; 1.29)). Conclusions Cohort studies may enhance cohort maintenance by paying particular attention to the subgroups that are most unlikely to respond and by an active recruitment strategy using telephone interviews.

Abstract Background To examine the association of education with body mass index (BMI) and waist circumference (WC) in the European Prospective Investigation into Cancer and Nutrition (EPIC). Method This study included 141,230 male and 336,637 female EPIC-participants, who were recruited between 1992 and 2000. Education, which was assessed by questionnaire, was classified into four categories; BMI and WC, measured by trained personnel in most participating centers, were modeled as continuous dependent variables. Associations were estimated using multilevel mixed effects linear regression models. Results Compared with the lowest education level, BMI and WC were significantly lower for all three higher education categories, which was consistent for all countries. Women with university degree had a 2.1 kg/m2 lower BMI compared with women with lowest education level. For men, a statistically significant, but less pronounced difference was observed (1.3 kg/m2). The association between WC and education level was also of greater magnitude for women: compared with the lowest education level, average WC of women was lower by 5.2 cm for women in the highest category. For men the difference was 2.9 cm. Conclusion In this European cohort, there is an inverse association between higher BMI as well as higher WC and lower education level. Public Health Programs that aim to reduce overweight and obesity should primarily focus on the lower educated population.

Mining and quarrying industry has recently made a shift towards underground exploitation as a viable alternative to traditional open-pit approaches. Thus, emerged the imperative need for localization systems for personnel safety and operations’ monitoring purposes. While there are many approaches taking advantage of the various signals of opportunity (SoO) supported by Internet of Things (IoT) for indoor and underground navigation, the need for a GNSS alternative in such areas is still present in terms of meeting system and user requirements (scale, cost, availability, accuracy, and integrity). The goal of this research is to provide insights regarding different Radio Frequency (RF) technologies operation and evaluate their positioning capabilities (Wi-Fi, BLE and LoRa) in underground industrial facilities such as quarries and mines, following and expanding the tests of previous studies in controlled environment. Furthermore, the multi-sensory approach that this study is pursuing, aims to provide the foundations of a low-cost, scalable and robust positioning system. This system would integrate the characteristics of the aforementioned technologies in order to meet the application-specific user requirements and set the basis for a more efficient mobile mapping system. In this context, technologies’ characterization and comparison is presented, by using data from a real operating underground quarry. The data gathered lead to the conceptualization of the localization scheme, which besides the SoO observables, utilizes their availability status as an additional feature within the quarry as well. The proposed combined approach outperformed the rest, achieving an accuracy bellow 15m for the 85% of the test data, which is sufficient for typical quarrying operations monitoring and management requirements.

Background: The intramedullary magnetic nail is an advanced technique in limb lengthening surgery, offering precise bone healing with minimal soft tissue disruption. However, increased use has led to a rise in periprosthetic fractures, and no standardized treatment protocols exist. This case report presents an innovative approach to managing such fractures without interrupting the limb lengthening process. Case report: A 21-year-old male with a 120mm limb length discrepancy, due to childhood osteomyelitis, underwent limb lengthening surgery with an intramedullary magnetic femoral nail. Twelve days postoperatively, he sustained a periprosthetic fracture around the proximal screws of the nail following a fall. We opted to continue the lengthening therapy by securing the fracture with a proximal femoral plate using one of the nail's screws. This approach allowed uninterrupted lengthening therapy. Follow-up confirmed stable fixation and successful limb lengthening, achieving an 80mm gain and reducing the discrepancy to 40mm. Conclusion: This case demonstrates a novel strategy for managing periprosthetic fractures during limb lengthening with intramedullary magnetic nails. By integrating the nail's proximal screw with a fixation plate, we enabled continued lengthening therapy and minimized additional surgical interventions. This approach underscores the need for further research to establish standardized protocols for managing such complications.

AimsThe COLchicine Cardiovascular Outcomes Trial (COLCOT) demonstrated the benefits of targeting inflammation after myocardial infarction (MI). We aimed to determine whether time-to-treatment initiation (TTI) influences the beneficial impact of colchicine.Methods and resultsIn COLCOT, patients were randomly assigned to receive colchicine or placebo within 30 days post-MI. Time-to-treatment initiation was defined as the length of time between the index MI and the initiation of study medication. The primary efficacy endpoint was a composite of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring coronary revascularization. The relationship between endpoints and various TTI (8 days) was examined using multivariable Cox regression models. Amongst the 4661 patients included in this analysis, there were 1193, 720, and 2748 patients, respectively, in the three TTI strata. After a median follow-up of 22.7 months, there was a significant reduction in the incidence of the primary endpoint for patients in whom colchicine was initiated < Day 3 compared with placebo [hazard ratios (HR) = 0.52, 95% confidence intervals (CI) 0.32-0.84], in contrast to patients in whom colchicine was initiated between Days 4 and 7 (HR = 0.96, 95% CI 0.53-1.75) or > Day 8 (HR = 0.82, 95% CI 0.61-1.11). The beneficial effects of early initiation of colchicine were also demonstrated for urgent hospitalization for angina requiring revascularization (HR = 0.35), all coronary revascularization (HR = 0.63), and the composite of cardiovascular death, resuscitated cardiac arrest, MI, or stroke (HR = 0.55, all P

Rationale: Oral treprostinil improves exercise capacity in patients with pulmonary arterial hypertension (PAH), but the effect on clinical outcomes was unknown.Objectives: To evaluate the effect of oral treprostinil compared with placebo on time to first adjudicated clinical worsening event in participants with PAH who recently began approved oral monotherapy.Methods: In this event-driven, double-blind study, we randomly allocated 690 participants (1:1 ratio) with PAH to receive placebo or oral treprostinil extended-release tablets three times daily. Eligible participants were using approved oral monotherapy for over 30 days before randomization and had a 6-minute-walk distance 150 m or greater. The primary endpoint was the time to first adjudicated clinical worsening event: death; hospitalization due to worsening PAH; initiation of inhaled or parenteral prostacyclin therapy; disease progression; or unsatisfactory long-term clinical response.Measurements and Main Results: Clinical worsening occurred in 26% of the oral treprostinil group compared with 36% of placebo participants (hazard ratio, 0.74; 95% confidence interval, 0.56-0.97; P = 0.028). Key measures of disease status, including functional class, Borg dyspnea score, and N-terminal pro-brain natriuretic peptide, all favored oral treprostinil treatment at Week 24 and beyond. A noninvasive risk stratification analysis demonstrated that oral treprostinil-assigned participants had a substantially higher mortality risk at baseline but achieved a lower risk profile from Study Weeks 12-60. The most common adverse events in the oral treprostinil group were headache, diarrhea, flushing, nausea, and vomiting.Conclusions: In participants with PAH, addition of oral treprostinil to approved oral monotherapy reduced the risk of clinical worsening.Clinical trial registered with www.clinicaltrials.gov (NCT01560624).

Post intensive care syndrome (PICS) affects an increasing number of critical illness survivors and their families, with serious physical and psychological sequelae. Since little is known about the burden of critical illness on ICU survivor families, we conducted a prospective observational study aiming to assess this, and investigate correlations of the patients’ psychometric and health-related quality of life (HRQOL) scores with family burden.

Data on COVID-19 mortality among patients in intensive care units (ICUs) from Eastern and/or Southern European countries, including Greece, are limited. The purpose of this study was to evaluate the ICU mortality trends among critically ill COVID-19 patients during the first two years of the pandemic in Greece and to further investigate if certain patients’ clinical characteristics contributed to this outcome. We conducted a multi-center retrospective observational study among five large university hospitals in Greece, between February 2020 and January 2022. All adult critically ill patients with confirmed COVID-19 disease who required ICU admission for at least 24 h were eligible. In total, 1462 patients (66.35% males) were included in this study. The mean age of this cohort was 64.9 (±13.27) years old. The 28-day mortality rate was 35.99% (n = 528), while the overall in-hospital mortality was 50.96% (n = 745). Cox regression analysis demonstrated that older age (≥65 years old), a body mass index within the normal range, and a delay in ICU admission from symptom onset, as well as worse baseline clinical severity scores upon ICU admission, were associated with a greater risk of death. Mortality of critically ill COVID-19 patients was high during the first two years of the pandemic in Greece but comparable to other countries. Risk factors for death presented in this study are not different from those that have already been described for COVID-19 in other studies.

BackgroundExperimental and clinical evidence supports the role of inflammation in atherosclerosis and its complications. Colchicine is an orally administered, potent antiinflammatory medication that is indicated for the treatment of gout and pericarditis.MethodsWe performed a randomized, double-blind trial involving patients recruited within 30 days after a myocardial infarction. The patients were randomly assigned to receive either low-dose colchicine (0.5 mg once daily) or placebo. The primary efficacy end point was a composite of death from cardiovascular causes, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina leading to coronary revascularization. The components of the primary end point and safety were also assessed.ResultsA total of 4745 patients were enrolled; 2366 patients were assigned to the colchicine group, and 2379 to the placebo group. Patients were followed for a median of 22.6 months. The primary end point occurred in 5.5% of the patients in the colchicine group, as compared with 7.1% of those in the placebo group (hazard ratio, 0.77; 95% confidence interval [CI], 0.61 to 0.96; P = 0.02). The hazard ratios were 0.84 (95% CI, 0.46 to 1.52) for death from cardiovascular causes, 0.83 (95% CI, 0.25 to 2.73) for resuscitated cardiac arrest, 0.91 (95% CI, 0.68 to 1.21) for myocardial infarction, 0.26 (95% CI, 0.10 to 0.70) for stroke, and 0.50 (95% CI, 0.31 to 0.81) for urgent hospitalization for angina leading to coronary revascularization. Diarrhea was reported in 9.7% of the patients in the colchicine group and in 8.9% of those in the placebo group (P = 0.35). Pneumonia was reported as a serious adverse event in 0.9% of the patients in the colchicine group and in 0.4% of those in the placebo group (P = 0.03).ConclusionsAmong patients with a recent myocardial infarction, colchicine at a dose of 0.5 mg daily led to a significantly lower risk of ischemic cardiovascular events than placebo. (Funded by the Government of Quebec and others; COLCOT ClinicalTrials.gov number, NCT02551094.).

This study explores the potential of satellite signals L5, E5a and B2a tracked by contemporary Android smartphones. Particularly, the objective is to investigate their performance capabilities and vulnerabilities concerned with L1, E1 and B1 bandwidths and a focus on land vehicle ITS (Intelligent Transportation Systems) applications aiming to address low to medium PVT (Positioning, Velocity and Timing) solutions. In this regard raw, kinematic GNSS measurements from two Android smartphones were collected (Xiaomi Mi 8 and One Plus Nord 2 5G) under GNSS-harsh environments. The Single Point Positioning (SPP) technique was adopted for processing the single-frequency, multi-constellation raw GNSS measurements through an Extended Kalman Filter (EKF). The results obtained indicate the benefits and difficulties of exploiting modernized GNSS signals for road ITS applications.

With the exponential development of MEMS (Micro-Electromechanical Systems) in the last decade, emphasis has been placed on the construction of IoT devices in conjunction with an appropriate information system to assist citizens in various fields (transportation, trade, etc.). More specifically, in the health sector,, there are specific IoT devices which can monitor a patient’s health condition or provide environmental data for the area, information which affects health quality conditions. In densely populated areas and especially in large cities, in terms of environmental pollution, as well as the known issue of air pollution, citizens are also exposed to solar radiation (ultraviolet UVA UVB radiation), as well as to noise pollution in areas where people live and work. Ultraviolet radiation, especially during the summer months, is responsible for skin cancer and various eye diseases, while noise pollution can create mental disorders in humans, especially in children. In this article, a low-cost solar radiation and noise pollution monitoring station is presented. The parts that compose the station and its implementation are a microcontroller (TTGO-OLED32) with an integrated LoRa device, an ultraviolet radiation sensor and sound sensors. In addition, a mini ups device is used in case of power failure and a GPS device is utilized for the location point. The measurements are obtained by the sensors every ten minutes and are transmitted via the LoRa network to an application server in which the user has direct access to the environmental data of a specific area. In conclusion, the data obtained from such IoT devices help in the study of cities to optimize factors in people’s lives.

Lithium-ion batteries are utilized everywhere from electronic equipment, smartphones and laptops to electric vehicles; however, certain disadvantages are inherited including high-cost and low-temperature range, caused by high currents. In this paper, a compact and low-cost battery management system is presented which can measure the voltage and current for both the battery and power supply. Two NTC thermistors, 10k and 100K Ohm each, are exploited for collecting battery temperature in two different spots of the socket for direct comparison and validation while an additional sensor measures external temperature and humidity. A charging socket is provided for charging the cell through an external source with dynamic voltage output to test the battery response. Finally, an Arduino-compatible device is implemented in order to protect the battery from overcharging. This system collects parameters at a 10 s time rate and calculates precious parameters of the battery-like State of Charge (SoC), State of Health (SoH) and State of Power (SoP). Keeping the operation within a safe zone of 20–80% SoC maximizes longevity and ensures that it can provide even the maximum power to cover the load required; hence, these three parameters are considered collaborative. Afterwards, the collected data are sent over Wi-Fi on the internet application server for real-time monitoring, in an efficient, portable and low-cost setup.

As the use and development of Internet of Things is very popular nowadays, one of the most widespread ways of exchanging data from such arrangements is the use of the LoRa network. One of the advantages offered by this technology is the ability to provide low power consumption as well as wide wireless coverage in an area. Although in research, there are references regarding the coverage radius of a geographical area, differences can be detected between urban (cities) and rural (countryside) areas, as in the latter, there are no dense structures nor radio signal noise inside the operating frequency spectrum of LoRa. Thus, results are expected to be better in rural areas than urban areas. Especially in an urban area, apart from the signal noise caused by other LoRa devices (either commercial or private), the coverage varies according to the placement of the LoRa station inside a building, which is related to the height at which the gateway is placed in another building. In this work, the LoRa radio coverage study is presented in a radius of 2 km both in an urban and a rural environment using only one LoRa gateway. To better capture the coverage, LoRa stations are placed on every floor of the selected buildings periodically. The results show the difference in coverage between urban and rural areas which is related to radio signal noise. Furthermore, significant changes in the coverage map in urban areas can be observed, directly related to the installation height of the LoRa station. With the understanding of these variations in LoRa network performance in different environments, informed decisions can be made regarding the deployment of such networks, optimizing their efficiency and ensuring seamless data transmission in both urban and rural settings.

Although many studies of the adolescent brain identified positive associations between cognitive abilities and cortical thickness, little is known about mechanisms underlying such brain-behavior relationships. With experience-induced plasticity playing an important role in shaping the cerebral cortex throughout life, it is likely that some of the inter-individual variations in cortical thickness could be explained by genetic variations in relevant molecular processes, as indexed by a polygenic score of neuronal plasticity (PGS-NP). Here, we studied associations between PGS-NP, cognitive abilities, and thickness of the cerebral cortex, estimated from magnetic resonance images, in the Saguenay Youth Study (SYS, 533 females, 496 males: age=15.0 ± 1.8 years of age; cross-sectional), and the IMAGEN Study (566 females, 556 males; between 14 and 19 years; longitudinal). Using Gene Ontology, we first identified 199 genes implicated in neuronal plasticity, which mapped to 155,600 single nucleotide polymorphisms (SNPs). Second, we estimated their effect sizes from an educational attainment meta-GWAS to build a PGS-NP. Third, we examined a possible moderating role of PGS-NP in the relationship between performance intelligence quotient (PIQ), and its subtests, and the thickness of 34 cortical regions.In SYS, we observed a significant interaction between PGS-NP and object assembly vis-à-vis thickness in male adolescents (p = 0.026). A median-split analysis showed that, in males with a ‘high’ PGS-NP, stronger associations between object assembly and thickness were found in regions with larger age-related changes in thickness (r = 0.55, p = 0.00075). Although the interaction between PIQ and PGS-NP was non-significant (p = 0.064), we performed a similar median-split analysis. Again, in the high PGS-NP males, positive associations between PIQ and thickness were observed in regions with larger age-related changes in thickness (r = 0.40, p = 0.018). In the IMAGEN cohort, we did not replicate the first set of results (interaction between PGS-NP and cognitive abilities via-a-vis cortical thickness) while we did observe the same relationship between the brain-behaviour relationship and (longitudinal) changes in cortical thickness (Matrix reasoning: r = 0.63, p = 6.5e-05). No statistically significant results were observed in female adolescents in either cohort. Overall, these cross-sectional and longitudinal results suggest that molecular mechanisms involved in neuronal plasticity may contribute to inter-individual variations of cortical thickness related to cognitive abilities during adolescence in a sex-specific manner.

Sleep is an important contributor for neural maturation and emotion regulation during adolescence, with long-term effects on a range of white matter tracts implicated in affective processing in at-risk populations. We investigated the effects of adolescent sleep patterns on longitudinal changes in white matter development and whether this is related to the emergence of emotional (internalizing) problems. Sleep patterns and internalizing problems were assessed using self-report questionnaires in adolescents recruited in the general population followed up from age 14–19 years (N = 111 White matter structure was measured using diffusion tensor imaging (DTI) and estimated using fractional anisotropy (FA). We found that longitudinal increases in time in bed (TIB) on weekends and increases in TIB-variability between weekdays to weekend, were associated with an increase in FA in various interhemispheric and cortico-striatal tracts. Extracted FA values from left superior longitudinal fasciculus mediated the relationship between increases in TIB on weekends and a decrease in internalizing problems. These results imply that while insufficient sleep might have potentially harmful effects on long-term white matter development and internalizing problems, longer sleep duration on weekends (catch-up sleep) might be a natural counteractive and protective strategy.