DNA methylation-based classification of central nervous system tumours.

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology

EEG Data Quality: Determinants and Impact in a Multicenter Study of Children, Adolescents, and Adults with Attention-Deficit/Hyperactivity Disorder (ADHD)

Electroencephalography (EEG) represents a widely established method for assessing altered and typically developing brain function. However, systematic studies on EEG data quality, its correlates, and consequences are scarce. To address this research gap, the current study focused on the percentage of artifact-free segments after standard EEG pre-processing as a data quality index. We analyzed participant-related and methodological influences, and validity by replicating landmark EEG effects. Further, effects of data quality on spectral power analyses beyond participant-related characteristics were explored. EEG data from a multicenter ADHD-cohort (age range 6 to 45 years), and a non-ADHD school-age control group were analyzed (ntotal = 305). Resting-state data during eyes open, and eyes closed conditions, and task-related data during a cued Continuous Performance Task (CPT) were collected. After pre-processing, general linear models, and stepwise regression models were fitted to the data. We found that EEG data quality was strongly related to demographic characteristics, but not to methodological factors. We were able to replicate maturational, task, and ADHD effects reported in the EEG literature, establishing a link with EEG-landmark effects. Furthermore, we showed that poor data quality significantly increases spectral power beyond effects of maturation and symptom severity. Taken together, the current results indicate that with a careful design and systematic quality control, informative large-scale multicenter trials characterizing neurophysiological mechanisms in neurodevelopmental disorders across the lifespan are feasible. Nevertheless, results are restricted to the limitations reported. Future work will clarify predictive value

Clozapine for Treatment-Resistant Bipolar Disorder: A Systematic Review

Objective To evaluate the efficacy and safety of clozapine for treatment-resistant bipolar disorder (TRBD). Methods A systematic review of randomized controlled studies, open-label prospective studies, and retrospective studies of patients with TRBD was carried out. Interventions included clozapine monotherapy or clozapine combined with other medications. Outcome measures were efficacy and adverse drug reactions (ADRs). Results Fifteen clinical trials with a total sample of 1,044 patients met the inclusion criteria. Clozapine monotherapy or clozapine combined with other treatments for TRBD was associated with improvement in: (i) symptoms of mania, depression, rapid cycling, and psychotic symptoms, with many patients with TRBD achieving a remission or response; (ii) the number and duration of hospitalizations, the number of psychotropic co-medications, and the number of hospital visits for somatic reasons for intentional self-harm/overdose; (iii) suicidal ideation and aggressive behavior; and (iv) social functioning. In addition, patients with TRBD showed greater clinical improvement in long-term follow-up when compared with published schizophrenia data. Sedation (12%), constipation (5.0%), sialorrhea (5.2%), weight gain (4%), and body ache/pain (2%) were the commonly reported ADRs; however, these symptoms but did not usually require drug discontinuation. The percentage of severe ADRs reported, such as leukopenia (2%), agranulocytosis (0.3%), and seizure (0.5%), appeared to be lower than those reported in the published schizophrenia literature. Conclusion The limited current evidence supports the concept that clozapine may be both an effective and a relatively safe medication for TRBD

O uso de textos polêmicos em sala de aula: formação e prática docente

O objetivo deste texto é duplo. Primeiro, analisa como Discursos, formas socialmente aceitas de falar/ouvir e escrever/ler sobre sujeitos em grupos sociais específicos (Gee, 2008), podem influenciar o uso ou a censura a textos polêmicos por docentes em sala de aula. Discute o que as pesquisas têm revelado sobre docentes utilizando em suas aulas o tema da diversidade. A partir de exemplo de livro de literatura sobre a temática do racismo, traz sugestões para que os professores possam conduzir discussões que respeitem a diversidade cultural de seus alunos e propiciem a formação de opiniões críticas, fazendo assim do professor da educação básica um sujeito responsivo

Heinrich Schenker’s Essential Voice: Tracing the Concept of an Essential Voice in Johann Sebastian Bach's Works for Solo Melodic Instruments

Heinrich Schenker’s theory of tonal voice leading is widely regarded for its ability to convey unique insight about common-practice tonal structure and composition. While the concept of an essential voice is implicit in Schenker’s theory of voice leading, he never directly addressed it. Without a broad formalization of the concept from Schenker, contemporary theorists provide inconsistent approaches that lead to competing interpretations and widely varying understanding of methodology. This thesis traces the latent concept of an essential voice in Schenker’s writings from Harmonielehre (1906) to Der freie Satz (1935) and provides analytical applications to the works of J. S. Bach—in particular his solo string works—to illustrate the value of the concept for contemporary Schenkerian theory. Chapter 1 lays the groundwork for a discussion of the essential voice concept by considering historical approaches to the idea of compound melody along with those of contemporary theorists. By drawing comparisons between strict and free tonal counterpoint, Chapter 2 develops the concept of identity for an essential voice as expressed by its registral position and ordering within contrapuntal layers. Chapter 3 grounds the concept of continuity for an essential voice in Schenker’s mentally retained note and rehabilitates the status of pedal tones as intermediate prolongational entities, framing essential voices as transformed pedal tones. Chapter 4 establishes the relationship between essential voice analyses and the musical surface foreground by historical analogy to thoroughbass and diminution theory. By differentiating between recursive, non-recursive, and terminating voice leading transformations it locates the essential voice-leading analysis as a late stage in the Schenkerian process of generative analysis. Chapter 5 illustrates the economy and clarity of essential voice-leading analysis through application to the Sarabande from J. S. Bach’s Suite No. 5 in C minor for Solo Cello, BWV 1011. This concluding chapter emphasizes that the essential voice properties of identity and continuity are derived solely and uniquely from the function of essential voices in composing out Stufen

Clearing and Pricing for Network-Aware Local Flexibility Markets using Distributed Optimization

Along with the rising installation of distributed en-ergy resources, the demand for flexibility and the management of such is of growing interest. This paper proposes a network-aware local flexibility market scheme, which is triggered by an upstream flexibility request and orchestrated by the distribution system operator (DSO). The consensus alternating direction method of multipliers (CADMM) is used to clear the market. The flexibility locational marginal price (FLMP) for each EC is derived from the nodal balance constraint. The market mechanism is tested using a ring network with a tie switch. The provision of flexibility and the formation of FLMP is analyzed considering a congested and non-congested state of the network. While no congestion occurs, the FLMP reaches an equilibrium price for all ECs. In case of congestion, the prices in the congested parts of the network drop, alongside an increase in the non-congested parts.</p

Clearing and Pricing for Network-Aware Local Flexibility Markets using Distributed Optimization

Along with the rising installation of distributed en-ergy resources, the demand for flexibility and the management of such is of growing interest. This paper proposes a network-aware local flexibility market scheme, which is triggered by an upstream flexibility request and orchestrated by the distribution system operator (DSO). The consensus alternating direction method of multipliers (CADMM) is used to clear the market. The flexibility locational marginal price (FLMP) for each EC is derived from the nodal balance constraint. The market mechanism is tested using a ring network with a tie switch. The provision of flexibility and the formation of FLMP is analyzed considering a congested and non-congested state of the network. While no congestion occurs, the FLMP reaches an equilibrium price for all ECs. In case of congestion, the prices in the congested parts of the network drop, alongside an increase in the non-congested parts.</p