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A recent genome-wide association study (GWAS) identified 12 independent loci significantly associated with attention-deficit/hyperactivity disorder (ADHD). Polygenic risk scores (PRS), derived from the GWAS, can be used to assess genetic overlap between ADHD and other traits. Using ADHD samples from several international sites, we derived PRS for ADHD from the recent GWAS to test whether genetic variants that contribute to ADHD also influence two cognitive functions that show strong association with ADHD: attention regulation and response inhibition, captured by reaction time variability (RTV) and commission errors (CE).
The discovery GWAS included 19 099 ADHD cases and 34 194 control participants. The combined target sample included 845 people with ADHD (age: 8–40 years). RTV and CE were available from reaction time and response inhibition tasks. ADHD PRS were calculated from the GWAS using a leave-one-study-out approach. Regression analyses were run to investigate whether ADHD PRS were associated with CE and RTV. Results across sites were combined via random effect meta-analyses.
When combining the studies in meta-analyses, results were significant for RTV (R2 = 0.011, β = 0.088, p = 0.02) but not for CE (R2 = 0.011, β = 0.013, p = 0.732). No significant association was found between ADHD PRS and RTV or CE in any sample individually (p > 0.10).
We detected a significant association between PRS for ADHD and RTV (but not CE) in individuals with ADHD, suggesting that common genetic risk variants for ADHD influence attention regulation.
More than 250 Pleistocene vertebrate trace fossil sites have been identified on the Cape south coast of South Africa in aeolianites and cemented foreshore deposits. These discoveries, representing the epifaunal tracks of animals that moved over these sand substrates, complement traditional body fossil studies, and contribute to palaeo-environmental reconstruction. Not described in detail until now, but also important faunal components, are the infaunal traces of animals that moved within these sandy substrates. Six golden mole burrow trace sites (Family Chrysochloridae) have been identified on the Cape south coast. In addition, three sites, including one on the Cape southeast coast, have been identified that show evidence of sand-swimming, probably by a golden mole with a means of locomotion similar to that of the extant Eremitalpa genus. Such traces have not been described in detail in the global ichnology record, and merit the erection of a new ichnogenus Natatorichnus, with two ichnospecies, N. subarenosa ichnosp. nov and N. sulcatus ichnosp. nov. Care is required in the identification of such traces, and the orientation of the trace fossil surface needs to be determined, to avoid confusion with hatchling turtle tracks. Substantial regional Pleistocene dune environments are inferred from these sand-swimming traces.
In this paper, we derive and analyse mean-field models for the dynamics of groups of individuals undergoing a random walk. The random motion of individuals is only influenced by the perceived densities of the different groups present as well as the available space. All individuals have the tendency to stay within their own group and avoid the others. These interactions lead to the formation of aggregates in case of a single species and to segregation in the case of multiple species. We derive two different mean-field models, which are based on these interactions and weigh local and non-local effects differently. We discuss existence and stability properties of solutions for both models and illustrate the rich dynamics with numerical simulations.
To compare cognitive phenotypes of participants with subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI), estimate progression to MCI/dementia by phenotype and assess classification error with machine learning.
Dataset consisted of 163 participants with SCD and 282 participants with aMCI from the Czech Brain Aging Study. Cognitive assessment included the Uniform Data Set battery and additional tests to ascertain executive function, language, immediate and delayed memory, visuospatial skills, and processing speed. Latent profile analyses were used to develop cognitive profiles, and Cox proportional hazards models were used to estimate risk of progression. Random forest machine learning algorithms reported cognitive phenotype classification error.
Latent profile analysis identified three phenotypes for SCD, with one phenotype performing worse across all domains but not progressing more quickly to MCI/dementia after controlling for age, sex, and education. Three aMCI phenotypes were characterized by mild deficits, memory and language impairment (dysnomic aMCI), and severe multi-domain aMCI (i.e., deficits across all domains). A dose–response relationship between baseline level of impairment and subsequent risk of progression to dementia was evident for aMCI profiles after controlling for age, sex, and education. Machine learning more easily classified participants with aMCI in comparison to SCD (8% vs. 21% misclassified).
Cognitive performance follows distinct patterns, especially within aMCI. The patterns map onto risk of progression to dementia.
In many domains of linguistics, theoretical differences have led to entrenchment and a certain degree of fragmentation. Morphology seems to be different. Theoretical positions differ substantially, but the differences never get in the way of informing oneself about the reasons for adhering to a different framework, making use of it. In this volume, the following frameworks are discussed: a-morphous morphology (Anderson 1992), word and paradigm morphology (Blevins 2016), paradigm function morphology (Stump 2001, 2016), onomasiological approaches (Dokulil 1962, Štekauer 1998), construction morphology (Booij 2010), lexical semantic framework (Lieber 2004, 2016), and neo-constructionist approaches (Hale & Keyser 2002) such as distributed morphology (Embick 2015). This volume thus contains a wealth of theoretical approaches, methodologies, and descriptive issues: a fitting tribute to a linguist who made it his hallmark to serve the linguistic community with a broad range of textbooks, monographs, and research articles.
Research into the experiences of those with a diagnosis of young onset dementia is extremely limited and the research that does exist tends to be loss orientated.
This paper will focus on a doctoral study which aimed to explore the full spectrum of lived experience of those with young onset dementia, whilst considering the unique impact of diagnosis at a younger age and the possibility of personal growth.
Five individuals took part in semi-structured interviews within which they were invited to bring along artefacts that helped them to share their experiences. Transcribed interviews were analysed using Interpretative Phenomenological Analysis and superordinate and subordinate themes were identified.
Four superordinate themes emerged: ‘Fear’, ‘Anger’, ‘Sadness’, ‘Contentment’ with thirteen subordinate themes. The findings indicated that participants experienced feelings of fear and vulnerability in response to their diagnosis. Participants felt angry that they did not have a voice, not enough was being done for those with dementia and they were being stereotyped. Participants spoke of a depressive state of mind in which they grieved for their past self, experienced isolation and loneliness, and feelings of hopelessness and despair. Finally, participants spoke of a sense of contentment in relation to a preserved self, a sense of living alongside their dementia and a desire to live in the present; making the most of the here and now.
The findings highlight the transitory nature of participants’ experiences as a result of multiple and repeated challenges to psychological equanimity. It suggested that these experiences could best be understood using lenses of lifespan development, bereavement and grief. The findings suggest that approaches to dementia care that focus on developing present-mindedness, acceptance and compassion may be particularly helpful.
In young patients, the cause of ischemic stroke (IS) remains often cryptogenic despite presence of traditional vascular risk factors (VRFs). Since arterial hypertension (AH) is considered the most important one, we aimed to evaluate the impact of AH and blood pressure (BP) levels after discharge on risk of recurrent IS (RIS) in young patients.
The study set consisted of acute IS patients < 50 years of age enrolled in the prospective Heart and Ischemic STrOke Relationship studY registered on ClinicalTrials.gov (NCT01541163). Cause of IS was assessed according to the ASCOD classification.
Out of 319 enrolled patients <50 years of age (179 males, mean age 41.1 ± 7.8 years), AH was present in 120 (37.6%) of them. No difference was found in the rates of etiological subtypes of IS between patients with and without AH. Patients with AH were older, had more VRF, used more frequently antiplatelets prior IS, and had more RIS (10 vs. 1%, p = 0.002) during a follow-up (FUP) with median of 25 months. Multivariate logistic regression stepwise model showed the prior use of antiplatelets as only predictor of RIS (p = 0.011, OR: 6.125; 95% CI: 1.510–24.837). Patients with elevated BP levels on BP Holter 1 month after discharge did not have increased rate of RIS during FUP (3.8 vs. 1.7%, p = 1.000).
AH occurred in 37.6% of young IS patients. Patients with AH had more frequently RIS. Prior use of antiplatelets was found only predictor of RIS in young IS patients with AH.
The principal aim of this study was to optimize the diagnosis of canine neuroangiostrongyliasis (NA). In total, 92 cases were seen between 2010 and 2020. Dogs were aged from 7 weeks to 14 years (median 5 months), with 73/90 (81%) less than 6 months and 1.7 times as many males as females. The disease became more common over the study period. Most cases (86%) were seen between March and July. Cerebrospinal fluid (CSF) was obtained from the cisterna magna in 77 dogs, the lumbar cistern in f5, and both sites in 3. Nucleated cell counts for 84 specimens ranged from 1 to 146 150 cells μL−1 (median 4500). Percentage eosinophils varied from 0 to 98% (median 83%). When both cisternal and lumbar CSF were collected, inflammation was more severe caudally. Seventy-three CSF specimens were subjected to enzyme-linked immunosorbent assay (ELISA) testing for antibodies against A. cantonensis; 61 (84%) tested positive, titres ranging from <100 to ⩾12 800 (median 1600). Sixty-one CSF specimens were subjected to real-time quantitative polymerase chain reaction (qPCR) testing using a new protocol targeting a bioinformatically-informed repetitive genetic target; 53/61 samples (87%) tested positive, CT values ranging from 23.4 to 39.5 (median 30.0). For 57 dogs, it was possible to compare CSF ELISA serology and qPCR. ELISA and qPCR were both positive in 40 dogs, in 5 dogs the ELISA was positive while the qPCR was negative, in 9 dogs the qPCR was positive but the ELISA was negative, while in 3 dogs both the ELISA and qPCR were negative. NA is an emerging infectious disease of dogs in Sydney, Australia.
Quantitative comparative social scientists have long worried about the performance of multilevel models when the number of upper-level units is small. Adding to these concerns, an influential Monte Carlo study by Stegmueller (2013) suggests that standard maximum-likelihood (ML) methods yield biased point estimates and severely anti-conservative inference with few upper-level units. In this article, the authors seek to rectify this negative assessment. First, they show that ML estimators of coefficients are unbiased in linear multilevel models. The apparent bias in coefficient estimates found by Stegmueller can be attributed to Monte Carlo Error and a flaw in the design of his simulation study. Secondly, they demonstrate how inferential problems can be overcome by using restricted ML estimators for variance parameters and a t-distribution with appropriate degrees of freedom for statistical inference. Thus, accurate multilevel analysis is possible within the framework that most practitioners are familiar with, even if there are only a few upper-level units.
Key features and applications of a unique atomic force microscope (AFM), the LiteScope™, which can be integrated into a scanning electron microscope (SEM) is reported. Using the AFM-in-SEM as one tool combines the capabilities of both systems in a very efficient way. The LiteScope design features advanced Correlative Probe and Electron Microscopy (CPEM)™ imaging technology that allows simultaneous acquisition of multiple AFM and SEM signals and their precise in-time correlation into a 3D CPEM view. AFM-in-SEM advantages are presented using several examples of applications and AFM measurement modes including CPEM, material electrical and mechanical properties together with nanoindentation, and focused ion beam (FIB) applications.
Antipsychotic medications may reduce hostile and aggressive behavior in schizophrenia. This study compared the effectiveness of antipsychotics in the treatment of aggression.
The Intercontinental Schizophrenia Outpatient Health Outcomes (IC-SOHO) study compares the effectiveness of antipsychotic treatments in practice setting. Schizophrenia outpatients who initiated or changed to a new antipsychotic are followed in this non-interventional, prospective observational study for up to 3 years, with 6-months data now available on the entire cohort (N = 7655). The presence or absence of verbal or physical hostility/aggression was assessed retrospectively for the period of 6 months before enrollment, and prospectively in the period of 6 months after enrollment (the study treatment period). At baseline, patients in five monotherapy treatment groups (combined N = 3135) were prescribed one of the treatments: clozapine, olanzapine, quetiapine, risperidone, or haloperidol, and had complete data.
Hostile/aggressive behavior was reduced during the treatment period. Olanzapine and risperidone were significantly superior to haloperidol and to clozapine in this respect. These results remained essentially unchanged when adjusting for baseline imbalances in age, gender, age of onset, and substance abuse.
As monotherapy, both olanzapine and risperidone were superior to haloperidol and clozapine in reducing aggression. The relative lack of effectiveness of clozapine may be specific to this study population.
Sexual dysfunction in patients with schizophrenia can reduce quality of life and treatment compliance. This report will compare the effects of selected atypical and typical antipsychotics on sexual function in a large, international population of outpatients with schizophrenia who were treated over 1 year.
Subjects and methods
Outpatients with schizophrenia, who initiated or changed antipsychotic treatment, and entered this 3-year, prospective, observational study were classified according to the monotherapy prescribed at baseline: olanzapine (N = 2638), risperidone (N = 860), quetiapine (N = 142) or haloperidol (N = 188).
Based on patient perception, the odds of experiencing sexual dysfunction during 1 year of therapy was significantly lower for patients treated with olanzapine and quetiapine when compared to patients who received risperidone or haloperidol (all P ≤ 0.001). Females on olanzapine (14%) or quetiapine (8%) experienced a lower rate of menstrual irregularities, compared to females on risperidone (23%) or haloperidol (29%). Significant discordance was evident between patient reports and psychiatrist perception of sexual dysfunction, with psychiatrists underestimating sexual dysfunction (P ≤ 0.001).
These findings indicate clinically relevant differences exist in the sexual side effect profiles of these selected antipsychotics. These factors should be considered when selecting the most appropriate treatment for outpatients with schizophrenia.
The Human Brain Project (HBP), an EU Flagship Initiative, is currently building an infrastructure that will allow integration of large amounts of heterogeneous neuroscience data. The ultimate goal of the project is to develop a unified multi-level understanding of the brain and its diseases, and beyond this to emulate the computational capabilities of the brain. Reference atlases of the brain are one of the key components in this infrastructure. Based on a new generation of three-dimensional (3D) reference atlases, new solutions for analyzing and integrating brain data are being developed. HBP will build services for spatial query and analysis of brain data comparable to current online services for geospatial data. The services will provide interactive access to a wide range of data types that have information about anatomical location tied to them. The 3D volumetric nature of the brain, however, introduces a new level of complexity that requires a range of tools for making use of and interacting with the atlases. With such new tools, neuroscience research groups will be able to connect their data to atlas space, share their data through online data systems, and search and find other relevant data through the same systems. This new approach partly replaces earlier attempts to organize research data based only on a set of semantic terminologies describing the brain and its subdivisions.
Here we provide an update of the 2013 report on the Nigerian Twin and Sibling Registry (NTSR). The major aim of the NTSR is to understand genetic and environmental influences and their interplay in psychological and mental health development in Nigerian children and adolescents. Africans have the highest twin birth rates among all human populations, and Nigeria is the most populous country in Africa. Due to its combination of large population and high twin birth rates, Nigeria has one of the largest twin populations in the world. In this article, we provide current updates on the NTSR samples recruited, recruitment procedures, zygosity assessment and findings emerging from the NTSR.
Values—the motivational goals that define what is important to us—guide our decisions and actions every day. Their importance is established in a long line of research investigating their universality across countries and their evolution from childhood to adulthood. In adolescence, value structures are subject to substantial change, as life becomes increasingly social. Value change has thus far been understood to operate independently within each person. However, being embedded in various social systems, adolescents are constantly subject to social influence from peers. Thus, we introduce a framework investigating the emergence and evolution of value priorities in the dynamic context of friendship networks. Drawing on stochastic actor-oriented network models, we analyze 73 friendship networks of adolescents. Regarding the evolution of values, we find that adolescents’ value systems evolve in a continuous cycle of internal validation through the selection and enactment of goals—thereby experiencing both congruence and conflicts—and external validation through social comparison among their friends. Regarding the evolution of friendship networks, we find that demographics are more salient for the initiation of new friendships, whereas values are more relevant for the maintenance of existing friendships.