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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.

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