A Novel Type I Receptor Serine-Threonine Kinase Predominantly Expressed in the Adult Central Nervous System*

Receptor serine-threonine kinases (RSTK) mediate inhibitory as well as stimulatory signals for growth and differentiation by binding to members of the transforming growth factor-beta (TGF-beta) superfamily. Over 12 different RSTKs have been isolated so far, displaying wide expression in peripheral tissues and in the nervous system. Here we report the isolation and characterization of a novel type I RSTK termed activin receptor-like kinase-7 (ALK-7) that, unlike other members of this receptor family, is predominantly expressed in the adult central nervous system. The ALK-7 gene encodes a 55-kDa cell-surface protein that exhibits up to 78% amino acid sequence identity in the kinase domain to previously isolated type I receptors for TGF-beta and activin. In the extracellular domain, however, ALK-7 is more divergent, displaying comparable similarities with all members of the ALK subfamily. RNase protection and in situ hybridization studies demonstrated a highly specific mRNA distribution restricted to neurons in several regions of the adult rat central nervous system, including cerebellum, hippocampus, and nuclei of the brainstem. Receptor reconstitution and cross-linking experiments indicated that ALK-7 can form complexes with type II RSTKs for TGF-beta and activin in a ligand-dependent manner, although direct binding of ALK-7 to ligand in these complexes could not be demonstrated. The specific expression pattern of ALK-7, restricted to the postnatal central nervous system, indicates that this receptor may play an important role in the maturation and maintenance of several neuronal subpopulations

Perception, cognition, and linguistic structure: The effect of linguistic modularity and cognitive style on sociolinguistic processing

The Interface Principle posits that morphosyntactic variation does not elicit the same kinds of perceptual reactions as phonetic variables because “members of the speech community evaluate the surface form of language but not more abstract structural features” (Labov, 1993:4). This article examines the effect of linguistic modularity on listeners’ social evaluations. Our point of departure is the sociolinguistic monitor, a hypothesized cognitive mechanism that governs frequency-linked perceptual awareness (Labov, Ash, Ravindranath, Weldon, & Nagy, 2011). Results indicate that “higher level” structural variables are available to the sociolinguistic monitor. Moreover, listeners’ reactions are conditioned by independent effects of region of provenance and individual cognitive style. Overall, our findings support the claim that sociolinguistic processing is influenced by a range of social and psychological constraints (Campbell-Kibler, 2011; Preston, 2010; Wagner & Hesson, 2014) while also demonstrating the need for models of sociolinguistic cognition to include patterns of grammatical variation (Meyerhoff & Walker, 2013; Walker, 2010)

Randomized trials fit for the 21st century. A joint opinion from the European Society of Cardiology, American Heart Association, American College of Cardiology, and the World Heart Federation

© The Author(s) 2022. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. When citing this article, a citation from any of the journals listed is appropriate. For commercial re-use, please contact [email protected] controlled trials are the cornerstone for reliably evaluating therapeutic strategies. However, during the past 25 years, the rules and regulations governing randomized trials and their interpretation have become increasingly burdensome, and the cost and complexity of trials has become prohibitive. The present model is unsustainable, and the development of potentially effective treatments is often stopped prematurely on financial grounds, while existing drug treatments or non-drug interventions (such as screening strategies or management tools) may not be assessed reliably. The current ‘best regulatory practice’ environment, and a lack of consensus on what that requires, too often makes it unduly difficult to undertake efficient randomized trials able to provide reliable evidence about the safety and efficacy of potentially valuable interventions. Inclusion of underrepresented population groups and lack of diversity also remain among the challenges.info:eu-repo/semantics/publishedVersio

Children's participation in preschool : A qualitative study with preschool teachers

Delaktighet är centralt begrepp i förskolan där förskollärare skall ansvara för att barnen blir delaktiga samt upplever delaktighet. Studiens syfte var att undersöka förskollärares beskrivningar, upplevelser och erfarenheter kring barns delaktighet i förskolan. I studien dras kopplingar i förhållande till det sociokulturella perspektivet där samspel och samarbete samt språk och kommunikation mellan människor ses som centrala. En kvalitativ forskningsansats har använts i studien där två fokusgruppintervjuer har utförts med tre verksamma förskollärare i respektive grupp. Urvalet utfördes utifrån ett bekvämlighetsurval vilket i studien innebär att forskarna har en tidigare koppling till rektorn för den enhet samt de förskolor de deltagande förskollärarna är verksamma i. Resultatets analys har inspirerats utifrån en fenomenografisk ansats. För att skapa förutsättningar för barns delaktighet i förskolan framkom det ur studiens resultat att förskollärarna ansåg det som centralt att skapa relationer och gemenskap med barnen och i barngruppen, att använda sig av dokumentation, att dela barngruppen i mindre grupper, att ha en god kommunikation och samsyn i arbetslaget samt att förskollärarnas barnsyn har en inverkan på huruvida delaktighet kommer till uttryck i förskolan

Classification of Adverse Events Following Surgery in Patients With Diffuse Lower-Grade Gliomas

Background: Recently, the Therapy-Disability-Neurology (TDN) was introduced as a multidimensional reporting system to detect adverse events in neurosurgery. The aim of this study was to compare the novel TDN score with the Landriel–Ibanez classification (LIC) grade in a large cohort of patients with diffuse lower-grade glioma (dLGG). Since the TDN score lacks validation against patient-reported outcomes, we described health-related quality of life (HRQoL) change in relation to TDN scores in a subset of patients. Methods: We screened adult patients with a surgically treated dLGG World Health Organization (WHO) grade 2 and 3 between 2010 and 2020. Up until 2017, it consists of a retrospective cohort (n = 158). From 2017 and onwards, HRQoL was registered using EuroQoL-5-dimension, three levels of response (EQ-5D 3L) questionnaire at baseline and 3 months follow-up, in a prospectively recruited cohort (n = 102). Both the LIC grade and TDN score were used to classify adverse events. Results: In total, 231 patients were included. In 110/231 (47.6%) of the surgical procedures, a postoperative complication was registered. When comparing the TDN score to LIC grades, only a minor shift towards complications of higher order could be observed. EQ-5D 3L was reported for 45 patients. Patients with complications related to surgery had pre- to postoperative changes in EQ-5D 3L index values (n = 27; mean 0.03, 95% CI −0.06 to 0.11) that were comparable to patients without complications (n = 18; mean −0.06, 95% CI −0.21 to 0.08). In contrast, patients with new-onset neurological deficit had a deterioration in HRQoL at follow-up, with a mean change in the EQ-5D 3L index value of 0.11 (n = 13, 95% CI 0.0 to 0.22) compared to −0.06 (n = 32, 95% CI −0.15 to 0.03) for all other patients. Conclusions: In patients with dLGG, TDN scores compared to the standard LIC tend to capture more adverse events of higher order. There was no clear relation between TDN severity and HRQoL. However, new-onset neurological deficit caused impairment in HRQoL. For the TDN score to better align with patient-reported outcomes, more emphasis on neurological deficit and function should be considered

Socioeconomic factors affect treatment delivery for patients with low grade glioma: a Swedish population-based study

Background Despite aspirations to achieve equality in healthcare we know that socioeconomic differences exist and may affect treatment and patient outcome, also in serious diseases such as cancer. We investigated disparities in neurosurgical care and outcome for patients with low-grade glioma (LGG). Methods In this nationwide registry-based study, patients who had undergone surgery for LGG during 2005–2015 were identified (n = 547) through the Swedish Brain Tumor Registry. We linked data to multiple national registries with individual level data on income, education and comorbidity and analyzed the association of disease characteristics, surgical management and outcome, with levels of income, education and sex. Results Patients with either low income, low education or female gender showed worse pre-operative performance status. Patients with low income or education also had more comorbidities and those with low education endured longer waiting times for surgery. Median time from radiological imaging to surgery was 51 days (Q1–3 27–191) for patients with low education, compared to 32 days (Q1–3 20–80) for patients with high education (p = 0.006). Differences in waiting time over educational levels remained significant after stratification for age, comorbidity, preoperative performance status, and tumor size. Overall survival was better for patients with high income or high education, but income- and education-related survival differences were not significant after adjustment for age and comorbidity. The type of surgical procedure or complications did not differ over socioeconomic groups or sex.Conclusion The neurosurgical care for LGG in Sweden, a society with universal healthcare, displays differences that can be related to socioeconomic factors

Psychotropic and anti-epileptic drug use, before and after surgery, among patients with low-grade glioma: a nationwide matched cohort study

Background: Low-grade glioma (LGG) is a relatively rare type of brain tumour. The use of antidepressant, sedative and anti-epileptic drugs can reflect the burden of the disease. While epilepsy is well-described in patients with LGG, less is known about depression and anxiety. Methods: We used nationwide registers to study the use (dispense) of antidepressants, sedatives, and anti-epileptic drugs (AEDs) before and after histopathological LGG diagnosis (WHO grade II). A total of 485 adult patients with a first-time diagnosis and a matched control cohort (n = 2412) were included. Patterns of use were analysed from one year prior to until one year following index date (date of surgery). Logistic regression analysis identified predictors for postoperative use. Results: At one year before index date, patients were dispensed AEDs 4 times more than controls, while antidepressants and sedatives were similar. Sedatives and AED peaked shortly after index date at 25 and 69%, respectively. AEDs then stabilized while sedatives decreased rapidly. For antidepressants, a delayed increase was seen after index date, stabilizing at 12%. At one year after index date, the use of antidepressants, sedatives, and AEDs among patients was 2, 3, and 26 times higher, respectively, compared to controls. Predictor for use of AEDs and sedatives at one year following index was previous use and/or a related diagnosis. Female sex and later index year were additional predictors for antidepressants. Conclusions: Use of antidepressants, sedatives and AEDs is elevated following diagnosis of LGG. Antidepressants were more commonly dispensed to female patients and in recent years

Psychotropic and anti-epileptic drug use, before and after surgery, among patients with low-grade glioma: a nationwide matched cohort study

Background: Low-grade glioma (LGG) is a relatively rare type of brain tumour. The use of antidepressant, sedative and anti-epileptic drugs can reflect the burden of the disease. While epilepsy is well-described in patients with LGG, less is known about depression and anxiety. Methods: We used nationwide registers to study the use (dispense) of antidepressants, sedatives, and anti-epileptic drugs (AEDs) before and after histopathological LGG diagnosis (WHO grade II). A total of 485 adult patients with a first-time diagnosis and a matched control cohort (n = 2412) were included. Patterns of use were analysed from one year prior to until one year following index date (date of surgery). Logistic regression analysis identified predictors for postoperative use. Results: At one year before index date, patients were dispensed AEDs 4 times more than controls, while antidepressants and sedatives were similar. Sedatives and AED peaked shortly after index date at 25 and 69%, respectively. AEDs then stabilized while sedatives decreased rapidly. For antidepressants, a delayed increase was seen after index date, stabilizing at 12%. At one year after index date, the use of antidepressants, sedatives, and AEDs among patients was 2, 3, and 26 times higher, respectively, compared to controls. Predictor for use of AEDs and sedatives at one year following index was previous use and/or a related diagnosis. Female sex and later index year were additional predictors for antidepressants. Conclusions: Use of antidepressants, sedatives and AEDs is elevated following diagnosis of LGG. Antidepressants were more commonly dispensed to female patients and in recent years

Socioeconomic factors affect treatment delivery for patients with low grade glioma : a Swedish population-based study

Background: Despite aspirations to achieve equality in healthcare we know that socioeconomic differences exist and may affect treatment and patient outcome, also in serious diseases such as cancer. We investigated disparities in neurosurgical care and outcome for patients with low-grade glioma (LGG). Methods: In this nationwide registry-based study, patients who had undergone surgery for LGG during 2005–2015 were identified (n = 547) through the Swedish Brain Tumor Registry. We linked data to multiple national registries with individual level data on income, education and comorbidity and analyzed the association of disease characteristics, surgical management and outcome, with levels of income, education and sex. Results: Patients with either low income, low education or female gender showed worse pre-operative performance status. Patients with low income or education also had more comorbidities and those with low education endured longer waiting times for surgery. Median time from radiological imaging to surgery was 51 days (Q1–3 27–191) for patients with low education, compared to 32 days (Q1–3 20–80) for patients with high education (p = 0.006). Differences in waiting time over educational levels remained significant after stratification for age, comorbidity, preoperative performance status, and tumor size. Overall survival was better for patients with high income or high education, but income- and education-related survival differences were not significant after adjustment for age and comorbidity. The type of surgical procedure or complications did not differ over socioeconomic groups or sex. Conclusion: The neurosurgical care for LGG in Sweden, a society with universal healthcare, displays differences that can be related to socioeconomic factors

Preoperative Patient-Reported Outcomes in Suspected Low-Grade Glioma : Markers of Disease Severity and Correlations with Molecular Subtypes

This prospective study aims to determine the overall health-related quality of life (HRQoL), functioning, fatigue, and psychological distress preoperatively in patients with suspected diffuse low-grade glioma (dLGG). We were particularly interested if these parameters differed by molecular tumor subtypes: oligodendroglioma, IDHmut astrocytoma and IDHwt astrocytoma. Fifty-one patients answered self-assessed questionnaires prior to operation (median age 51 years; range 19-75; 19 females [37%]). Thirty-five (69%) patients had IDH-mutated tumors, of which 17 were 1p/19q codeleted (i.e., oligodendroglioma) and 18 non-1p/19q codeleted (i.e., IDHmut astrocytoma). A lower overall generic HRQoL was associated with a high level of fatigue (rs = -0.49, p < 0.001), visual disorder (rs = -0.5, p < 0.001), motor dysfunction (rs = -0.51, p < 0.001), depression (rs = -0.54, p < 0.001), and reduced functioning. Nearly half of the patients reported high fatigue (23 out of 51 patients) and anxiety (26/51 patients). Patients with IDHwt had worse generic HRQoL, worse functioning, and more severe fatigue, though differences were not statistically significant between the molecular subtypes. In conclusion, fatigue and anxiety are prominent self-assessed symptoms of patients with suspected dLGG in a preoperative setting, but do not seem to be a reliable method to make assumptions of underlying biology or guide treatment decisions