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Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement.
Methods
We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes.
Results
We replicated the well-known association at the CHRNA5 locus (lead single-nucleotide polymorphism [SNP]: rs147144681, p = 1.27E−11 in EUR; lead SNP = rs2036527, p = 6.49e−13 in cross-ancestry analysis). DSM-NicDep showed strong positive genetic correlations with cannabis use disorder, opioid use disorder, problematic alcohol use, lung cancer, material deprivation, and several psychiatric disorders, and negative correlations with respiratory function and educational attainment. A polygenic score of DSM-NicDep predicted DSM-5 tobacco use disorder criterion count and all 11 individual diagnostic criteria in the independent National Epidemiologic Survey on Alcohol and Related Conditions-III sample. In genomic structural equation models, DSM-NicDep loaded more strongly on a previously identified factor of general addiction liability than a “problematic tobacco use” factor (a combination of cigarettes per day and nicotine dependence defined by the Fagerström Test for Nicotine Dependence). Finally, DSM-NicDep showed a strong genetic correlation with a GWAS of tobacco use disorder as defined in electronic health records (EHRs).
Conclusions
Our results suggest that combining the wide availability of diagnostic EHR data with nuanced criterion-level analyses of DSM tobacco use disorder may produce new insights into the genetics of this disorder.
Many studies have highlighted the detrimental effect of childhood maltreatment (CM) on depression severity and the course of illness in major depressive disorder (MDD). Yet our understanding of how CM influences the dynamic symptom change throughout a patient’s trajectory remains limited. Hence, we investigated the impact of CM on depression severity in MDD with a focus on various treatment phases during inpatient treatment and after discharge (1 or 2 years later) and validated findings in a real-world setting.
Methods
We used longitudinal data from a cohort study sample (n = 567) and a clinical routine sample (n = 438). CM was measured with the Childhood Trauma Questionnaire (CTQ), and depression severity was assessed using Beck’s Depression Inventory (BDI). The long-term clinical trajectory was assessed using the Life Chart Interview.
Results
Our analyses revealed that CM significantly increased depression severity before, during, and after inpatient therapy in both samples. Although CM was associated with higher depression severity at the beginning of inpatient treatment and lower remission rates upon discharge, no discernible impact of CM was evident on the relative change in symptoms over time during inpatient treatment. CM consistently predicted higher relapse rates and lower rates of full remission after discharge during long-term follow-up in both samples.
Conclusions
Our findings affirm the link between CM and the development of more severe and persistent clinical trajectories within real-world clinical settings. Furthermore, conventional psychiatric treatments may not lead to comparable outcomes for individuals with a history of CM, underscoring the necessity for tailored therapeutic interventions.
The Lyman alpha (Ly$\alpha$) forest in the spectra of $z\gt5$ quasars provides a powerful probe of the late stages of the epoch of reionisation (EoR). With the recent advent of exquisite datasets such as XQR-30, many models have struggled to reproduce the observed large-scale fluctuations in the Ly$\alpha$ opacity. Here we introduce a Bayesian analysis framework that forward-models large-scale lightcones of intergalactic medium (IGM) properties and accounts for unresolved sub-structure in the Ly$\alpha$ opacity by calibrating to higher-resolution hydrodynamic simulations. Our models directly connect physically intuitive galaxy properties with the corresponding IGM evolution, without having to tune ‘effective’ parameters or calibrate out the mean transmission. The forest data, in combination with UV luminosity functions and the CMB optical depth, are able to constrain global IGM properties at percent level precision in our fiducial model. Unlike many other works, we recover the forest observations without invoking a rapid drop in the ionising emissivity from $z\sim7$ to 5.5, which we attribute to our sub-grid model for recombinations. In this fiducial model, reionisation ends at $z=5.44\pm0.02$ and the EoR mid-point is at $z=7.7\pm0.1$. The ionising escape fraction increases towards faint galaxies, showing a mild redshift evolution at fixed UV magnitude, $M_\textrm{UV}$. Half of the ionising photons are provided by galaxies fainter than $M_\textrm{UV} \sim -12$, well below direct detection limits of optical/NIR instruments including $\textit{ JWST}$. We also show results from an alternative galaxy model that does not allow for a redshift evolution in the ionising escape fraction. Despite being decisively disfavoured by the Bayesian evidence, the posterior of this model is in qualitative agreement with that from our fiducial model. We caution, however, that our conclusions regarding the early stages of the EoR and which sources reionised the Universe are more model-dependent.
The COVID-19 pandemic has had a significant impact on the health of millions of people worldwide, and many manifest new or persistent symptoms long after the initial onset of the infection. One of the leading symptoms of long-COVID is cognitive impairment, which includes memory loss, lack of concentration, and brain fog. Understanding the nature and underlying mechanisms of cognitive impairment in long-COVID is important for developing preventive and therapeutic interventions.
Methods
Our present study investigated functional connectivity (FC) changes in patients with long-COVID and their associations with cognitive impairment. Resting-state functional MRI data from 60 long-COVID patients and 52 age- and sex-matched healthy controls were analyzed using seed-based functional connectivity analysis.
Results
We found increased FC between the right caudate nucleus and both the left and right precentral gyri in long-COVID patients compared with healthy controls. In addition, elevated FC was observed between the right anterior globus pallidus and posterior cingulate cortex as well as the right temporal pole in long-COVID patients. Importantly, the magnitude of FC between the caudate and the left precentral gyrus showed a significant negative correlation with Montreal Cognitive Assessment (MoCA) scores and a negative correlation with Trail Making Test B performance in the patient group.
Conclusion
Patients with long-COVID present enhanced FC between the caudate and the left precentral gyrus. Furthermore, those FC alterations are related to the severity of cognitive impairment, particularly in the domain of executive functions.
Major depressive disorder (MDD) is characterized by changes in appetite and body weight as well as blunted reward sensitivity (‘anhedonia’). However, it is not well understood which mechanisms are driving changes in reward sensitivity, specifically regarding food. Here, we used a sample of 117 participants (54 patients with MDD and 63 healthy control participants [HCPs]) who completed a food cue reactivity task with ratings of wanting and liking for 60 food and 20 non-food items. To evaluate which components of the food may contribute to altered ratings in depression, we tested for associations with macronutrients of the depicted items. In line with previous studies, we found reduced ratings of food wanting (p = .003) but not liking (p = .23) in patients with MDD compared to matched HCPs. Adding macronutrient composition to the models of wanting and liking substantially improved their fit (ps < .001). Compared to carbohydrate-rich foods, patients with MDD reported lower liking and wanting ratings for high-fat and high-protein foods. Moreover, patients with MDD showed weaker correlations in their preferences for carbohydrate- versus fat- or protein-rich foods (ps < .001), pointing to potential disturbances in metabolic signaling. To conclude, our results suggest that depression-related alterations in food reward ratings are more specific to the macronutrient composition of the food than previously anticipated, hinting at disturbances in gut–brain signaling. These findings raise the intriguing question of whether interventions targeting the gut could help normalize aberrant reward signals for foods rich in fat or protein.
Observations of glacier melt and runoff are of fundamental interest in the study of glaciers and their interactions with their environment. Considerable recent interest has developed around distributed acoustic sensing (DAS), a sensing technique which utilizes Rayleigh backscatter in fiber optic cables to measure the seismo-acoustic wavefield in high spatial and temporal resolution. Here, we present data from a month-long, 9 km DAS deployment extending through the ablation and accumulation zones on Rhonegletscher, Switzerland, during the 2020 melt season. While testing several types of machine learning (ML) models, we establish a regression problem, using the DAS data as the dependent variable, to infer the glacier discharge observed at a proglacial stream gauge. We also compare two predictive models that only depend on meteorological station data. We find that the seismo-acoustic wavefield recorded by DAS can be utilized to infer proglacial discharge. Models using DAS data outperform the two models trained on meteorological data with mean absolute errors of 0.64, 2.25 and 2.72 m3 s−1, respectively. This study demonstrates the ability of in situ glacier DAS to be used for quantifying proglacial discharge and points the way to a new approach to measuring glacier runoff.
High cognitive activity possibly reduces the risk of cognitive decline and dementia.
Aims
To investigate associations between an individual's need to engage in cognitively stimulating activities (need for cognition, NFC) and structural brain damage and cognitive functioning in the Dutch general population with and without existing cognitive impairment.
Method
Cross-sectional data were used from the population-based cohort of the Maastricht Study. NFC was measured using the Need For Cognition Scale. Cognitive functioning was tested in three domains: verbal memory, information processing speed, and executive functioning and attention. Values 1.5 s.d. below the mean were defined as cognitive impairment. Standardised volumes of white matter hyperintensities (WMH), cerebrospinal fluid (CSF) and presence of cerebral small vessel disease (CSVD) were derived from 3T magnetic resonance imaging. Multiple linear and binary logistic regression analyses were used adjusted for demographic, somatic and lifestyle factors.
Results
Participants (n = 4209; mean age 59.06 years, s.d. = 8.58; 50.1% women) with higher NFC scores had higher overall cognition scores (B = 0.21, 95% CI 0.17–0.26, P < 0.001) and lower odds for CSVD (OR = 0.74, 95% CI 0.60–0.91, P = 0.005) and cognitive impairment (OR = 0.60, 95% CI 0.48–0.76, P < 0.001) after adjustment for demographic, somatic and lifestyle factors. The association between NFC score and cognitive functioning was similar for individuals with and without prevalent cognitive impairment. We found no significant association between NFC and WMH or CSF volumes.
Conclusions
A high need to engage in cognitively stimulating activities is associated with better cognitive functioning and less presence of CSVD and cognitive impairment. This suggests that, in middle-aged individuals, motivation to engage in cognitively stimulating activities may be an opportunity to improve brain health.
Late-life depression has been associated with volume changes of the hippocampus. However, little is known about its association with specific hippocampal subfields over time.
Aims
We investigated whether hippocampal subfield volumes were associated with prevalence, course and incidence of depressive symptoms.
Method
We extracted 12 hippocampal subfield volumes per hemisphere with FreeSurfer v6.0 using T1-weighted and fluid-attenuated inversion recovery 3T magnetic resonance images. Depressive symptoms were assessed at baseline and annually over 7 years of follow-up (9-item Patient Health Questionnaire). We used negative binominal, logistic, and Cox regression analyses, corrected for multiple comparisons, and adjusted for demographic, cardiovascular and lifestyle factors.
Results
A total of n = 4174 participants were included (mean age 60.0 years, s.d. = 8.6, 51.8% female). Larger right hippocampal fissure volume was associated with prevalent depressive symptoms (odds ratio (OR) = 1.26, 95% CI 1.08–1.48). Larger bilateral hippocampal fissure (OR = 1.37–1.40, 95% CI 1.14–1.71), larger right molecular layer (OR = 1.51, 95% CI 1.14–2.00) and smaller right cornu ammonis (CA)3 volumes (OR = 0.61, 95% CI 0.48–0.79) were associated with prevalent depressive symptoms with a chronic course. No associations of hippocampal subfield volumes with incident depressive symptoms were found. Yet, lower left hippocampal amygdala transition area (HATA) volume was associated with incident depressive symptoms with chronic course (hazard ratio = 0.70, 95% CI 0.55–0.89).
Conclusions
Differences in hippocampal fissure, molecular layer and CA volumes might co-occur or follow the onset of depressive symptoms, in particular with a chronic course. Smaller HATA was associated with an increased risk of incident (chronic) depression. Our results could capture a biological foundation for the development of chronic depressive symptoms, and stresses the need to discriminate subtypes of depression to unravel its biological underpinnings.
We carried out a comparative analysis between the bacterial microbiota composition of zoo-housed western lowland gorillas and their wild counterparts through 16S rRNA gene amplicon sequencing. In addition, we characterised the carbohydrate-active and methanogenic potential of the zoo-housed gorilla (ZHG) microbiome through shotgun metagenomics and RNA sequencing. The ZHG microbiota showed increased alpha diversity in terms of bacterial species richness and a distinct composition from that of the wild gorilla microbiota, including a loss of abundant fibre-degrading and hydrogenic Chloroflexi. Metagenomic analysis of the CAZyome indicated predominant oligosaccharide-degrading activity, while RNA sequencing revealed diverse cellulase and hemi-cellulase activities in the ZHG gut, contributing to a total of 268 identified carbohydrate-active enzymes. Metatranscriptome analysis revealed a substantial contribution of 38% of the transcripts from anaerobic fungi and archaea to the gorilla microbiome. This activity originates from cellulose-degrading and hydrogenic fungal species belonging to the class Neocallimastigomycetes, as well as from methylotrophic and hydrogenotrophic methanogenic archaea belonging to the classes Thermoplasmata and Methanobacteria, respectively. Our study shows the added value of RNA sequencing in a multiomics approach and highlights the contribution of eukaryotic and archaeal activities to the gut microbiome of gorillas.
The question under which circumstances an undertaking is liable for its own competition law infringement – not to mention the liability for infringements committed by an affiliated undertaking – is of invaluable practical importance. From the early days of European competition law, there has been an interesting legal relationship between the single economic entity as the addressee of EU competition law and the respective entities under national corporate laws. Legend has it, businesses in some European jurisdictions can avoid fines by way of corporate restructuring, whilst in other jurisdictions this is not an option. The present contribution traces the developments in the EU and in Germany during recent years with special regard to the so-called German sausage gap – a once well-known and much-exploited lacuna that helped shelter companies from liability through specific corporate restructuring.
Randomised controlled trials (RCTs) have provided considerable evidence for the short-term efficacy of cognitive behavioural therapy (CBT) in children and adolescents with depressive and anxiety disorders. However, the effectiveness and long-term stability of treatment effects under routine care conditions remain unproven.
Aims:
This observational study investigates the effectiveness and stability of CBT under routine care conditions within a large sample of clinically referred youth with depressive and anxiety disorders.
Method:
Two hundred and twenty former patients (age 6–18 years at start of treatment) underwent a follow-up assessment (follow-up interval: M=5.3 years, SD=2.47). Parent and self-ratings of behavioural and emotional problems were obtained at the beginning and end of treatment and at follow-up. Additionally, at follow-up, a telephone interview and questionnaires exploring other mental symptoms and life satisfaction were administered.
Results:
A repeated measures ANOVA yielded statistically significant, medium to large pre– post symptom reductions (ηp2=.15 to ηp²=.47) and small to medium post-follow-up symptom reductions (ηp²=.03 to ηp²=.19). At follow-up, between 57 and 70% of the sample reported a decrease in different emotional symptoms since the end of treatment, and 80% reported improved life satisfaction.
Conclusions:
These findings provide evidence for the effectiveness and stability of treatment effects of CBT in youth with depressive and anxiety disorders under routine care conditions. Due to the lack of a direct control condition and a substantial proportion of missing data, the results must be interpreted with caution.
Current psychiatric diagnoses, although heritable, have not been clearly mapped onto distinct underlying pathogenic processes. The same symptoms often occur in multiple disorders, and a substantial proportion of both genetic and environmental risk factors are shared across disorders. However, the relationship between shared symptoms and shared genetic liability is still poorly understood.
Aims
Well-characterised, cross-disorder samples are needed to investigate this matter, but few currently exist. Our aim is to develop procedures to purposely curate and aggregate genotypic and phenotypic data in psychiatric research.
Method
As part of the Cardiff MRC Mental Health Data Pathfinder initiative, we have curated and harmonised phenotypic and genetic information from 15 studies to create a new data repository, DRAGON-Data. To date, DRAGON-Data includes over 45 000 individuals: adults and children with neurodevelopmental or psychiatric diagnoses, affected probands within collected families and individuals who carry a known neurodevelopmental risk copy number variant.
Results
We have processed the available phenotype information to derive core variables that can be reliably analysed across groups. In addition, all data-sets with genotype information have undergone rigorous quality control, imputation, copy number variant calling and polygenic score generation.
Conclusions
DRAGON-Data combines genetic and non-genetic information, and is available as a resource for research across traditional psychiatric diagnostic categories. Algorithms and pipelines used for data harmonisation are currently publicly available for the scientific community, and an appropriate data-sharing protocol will be developed as part of ongoing projects (DATAMIND) in partnership with Health Data Research UK.
Future mass loss projections of the Greenland ice sheet require understanding of the processes at a glacier terminus, especially of iceberg calving. We present detailed and high-rate terrestrial radar interferometer observations of Eqip Sermia and Bowdoin Glacier, two outlet glaciers in Greenland with comparable dimensions and investigate iceberg calving, surface elevation, velocity, strain rates and their links to air temperature, tides and topography. The results reveal that the two glaciers exhibit very different flow and calving behaviour on different timescales. Ice flow driven by a steep surface slope with several topographic steps leads to high velocities, areas of extension and intense crevassing, which triggers frequent but small calving events independent of local velocity gradients. In contrast, ice flow under smooth surface slopes leaves the ice relatively intact, such that sporadic large-scale calving events dominate, which initiate in areas with high shearing. Flow acceleration caused by enhanced meltwater input and tidal velocity variations were observed for terminus sections close to floatation. Firmly grounded terminus sections showed no tidal signal and a weak short-term reaction to air temperature. These results demonstrate reaction timescales to external forcings from hours to months, which are, however, strongly dependent on local terminus geometry.
In 2017, a point-prevalence survey was conducted with 12,931 patients in 96 hospitals across Switzerland as part of the national strategy to prevent healthcare-associated infections (HAIs). We present novel statistical methods to assess incidence proportions of HAI and attributable length-of-stay (LOS) in point-prevalence surveys.
Methods:
Follow-up data were collected for a subsample of patients and were used to impute follow-up data for all remaining patients. We used weights to correct length bias in logistic regression and multistate analyses. Methods were also tested in simulation studies.
Results:
The estimated incidence proportion of HAIs during hospital stay and not present at admission was 2.3% (95% confidence intervals [CI], 2.1–2.6), the most common type being lower respiratory tract infections (0.8%; 95% CI, 0.6–1.0). Incidence proportion was highest in patients with a rapidly fatal McCabe score (7.8%; 95% CI, 5.7–10.4). The attributable LOS for all HAI was 6.4 days (95% CI, 5.6–7.3) and highest for surgical site infections (7.1 days, 95% CI, 5.2–9.0). It was longest in the age group of 18–44 years (9.0 days; 95% CI, 5.4–12.6). Risk-factor analysis revealed that McCabe score had no effect on the discharge hazard after infection (hazard ratio [HR], 1.21; 95% CI, 0.89–1.63). Instead, it only influenced the infection hazard (HR, 1.84; 95% CI, 1.39–2.43) and the discharge hazard prior to infection (HR, 0.73; 95% CI, 0.66–0.82).
Conclusions:
In point-prevalence surveys with limited follow-up data, imputation and weighting can be used to estimate incidence proportions and attributable LOS that would otherwise require complete follow-up data.
Substantial progress has been made in the standardization of nomenclature for paediatric and congenital cardiac care. In 1936, Maude Abbott published her Atlas of Congenital Cardiac Disease, which was the first formal attempt to classify congenital heart disease. The International Paediatric and Congenital Cardiac Code (IPCCC) is now utilized worldwide and has most recently become the paediatric and congenital cardiac component of the Eleventh Revision of the International Classification of Diseases (ICD-11). The most recent publication of the IPCCC was in 2017. This manuscript provides an updated 2021 version of the IPCCC.
The International Society for Nomenclature of Paediatric and Congenital Heart Disease (ISNPCHD), in collaboration with the World Health Organization (WHO), developed the paediatric and congenital cardiac nomenclature that is now within the eleventh version of the International Classification of Diseases (ICD-11). This unification of IPCCC and ICD-11 is the IPCCC ICD-11 Nomenclature and is the first time that the clinical nomenclature for paediatric and congenital cardiac care and the administrative nomenclature for paediatric and congenital cardiac care are harmonized. The resultant congenital cardiac component of ICD-11 was increased from 29 congenital cardiac codes in ICD-9 and 73 congenital cardiac codes in ICD-10 to 318 codes submitted by ISNPCHD through 2018 for incorporation into ICD-11. After these 318 terms were incorporated into ICD-11 in 2018, the WHO ICD-11 team added an additional 49 terms, some of which are acceptable legacy terms from ICD-10, while others provide greater granularity than the ISNPCHD thought was originally acceptable. Thus, the total number of paediatric and congenital cardiac terms in ICD-11 is 367. In this manuscript, we describe and review the terminology, hierarchy, and definitions of the IPCCC ICD-11 Nomenclature. This article, therefore, presents a global system of nomenclature for paediatric and congenital cardiac care that unifies clinical and administrative nomenclature.
The members of ISNPCHD realize that the nomenclature published in this manuscript will continue to evolve. The version of the IPCCC that was published in 2017 has evolved and changed, and it is now replaced by this 2021 version. In the future, ISNPCHD will again publish updated versions of IPCCC, as IPCCC continues to evolve.
The design and first experimental results of Tx and Rx L-band bandpass filters for a high-power satellite diplexer are presented in this paper. Designed in the framework of an ESA ARTES AT project, the filters are based on TM010 mode dielectric resonators. These resonators allow for better results in terms of volume occupation with respect to other dielectric resonators still maintaining high Q-factor values (>2000). Volume saving above 30% is achieved with respect to standard coaxial filters. The filter geometries and materials have been chosen in order to improve the power-handling and to cope with related critical issues for space applications (i.e. avoid any multipactor discharge in the operating RF power range and low-PIM response). Measurements of Tx filter show good correlation with the design in terms of central frequency, BW, and unloaded Q-factor (almost 3000). Measurements of Rx filter show a worse correlation with the design in terms of filter response shape. This is ascribed to size tolerances of one of the filter resonators. Multiple analyses are ongoing to remove this degradation in the final engineering model.
Infant neurodevelopment is a complex process which may be affected by different events during pregnancy, such as hypertensive disorders of pregnancy (HDP). We conducted a prospective cohort study to compare the prevalence of neurodevelopmental disorders in infants born to mothers with and without HDP at six months of age. Participants attended the Health Observatory of Instituto de Desarrollo e Investigaciones Pediátricas “Prof. Dr. Fernando E. Viteri” during 2018 and 2019. Infant neurodevelopment was assessed with the Bayley Scales of Infant and Toddler Development—Third Edition (Bayley-III). Data were analyzed using Chi-square, Student’s t-test and Mann–Whitney test. Of the 132 participating infants, 68 and 64 were born to mothers with and without HDP, respectively. At six months, the prevalence of risk of neurodevelopmental delay was significantly higher in infants born to mothers with than without HDP (27.9% vs. 9.4%; p = 0.008) (odds ratio, 3.71; 95% confidence interval, 1.30; 12.28). In conclusion, infants born to mothers with HDP had three times increased risk of neurodevelopmental delay at six months of age.
Mood plays an important role in our life which is illustrated by the disruptive impact of aberrant mood states in depression. Although vagus nerve stimulation (VNS) has been shown to improve symptoms of depression, the exact mechanism is still elusive, and it is an open question whether non-invasive VNS could be used to swiftly and robustly improve mood.
Methods
Here, we investigated the effect of left- and right-sided transcutaneous auricular VNS (taVNS) v. a sham control condition on mood after the exertion of physical and cognitive effort in 82 healthy participants (randomized cross-over design) using linear mixed-effects and hierarchical Bayesian analyses of mood ratings.
Results
We found that 90 min of either left-sided or right-sided taVNS improved positive mood [b = 5.11, 95% credible interval, CI (1.39–9.01), 9.6% improvement relative to the mood intercept, BF10 = 7.69, pLME = 0.017], yet only during the post-stimulation phase. Moreover, lower baseline scores of positive mood were associated with greater taVNS-induced improvements in motivation [r = −0.42, 95% CI (−0.58 to −0.21), BF10 = 249].
Conclusions
We conclude that taVNS boosts mood after a prolonged period of effort exertion with concurrent stimulation and that acute motivational effects of taVNS are partly dependent on initial mood states. Collectively, our results show that taVNS may help quickly improve affect after a mood challenge, potentially by modulating interoceptive signals contributing to the reappraisal of effortful behavior. This suggests that taVNS could be a useful add-on to current behavioral therapies.