Children at the Crossroads of Opportunities and Constraints: The relationship between school and family from the children’s viewpoint: their perspectives, their positions. Bertelsmann Stiftung Summary Research Report 2 August 2020.

What do primary-school students have to say about formal meetings between parents and teachers? How do they feel about more informal exchanges? What do children think of these interactions and which role do they themselves adopt? Those are the questions addressed by the second research report Children at the Crossroads of Opportunities and Constraints,1 authored by Tanja Betz of Johannes Gutenberg University Mainz and her team as part of a project jointly carried out with the Bertelsmann Stiftung. The report focuses on children – actors previously neglected in the academic and policy debates – by investigating their feelings about what makes a “good” educational partnership between families and schools. During group discussions and individual interviews, the researchers spoke with students in the third and fourth grades at five mainstream primary schools in the states of Hesse and Rhineland–Palatinate. Their goal was to learn more about how the family-school relationship is shaped. As the findings clearly show: Children have more than just one perspective and are not a homogenous group – the same way parents and educational professionals are not. Some want to be informed and involved when their parents interact with teachers or others at school. As they see it, they benefit from a close connection between their family and school. They are pleased when their mother or father comes to school and they themselves can have a say – for example, during parent-teacher-student conferences. The findings suggest, however, that this applies more to children from socially advantaged families. Other children, in contrast, attempt to keep the worlds of family and school as separate as possible. One child explained that in his free time he is “a different person than at school” and that this “free-time me” or “at-home me” should remain unknown at school as much as possible. Some children, however, do not succeed in controlling the flow of information between their parents and school on topics they consider “private.” Parents divulge “secrets” instead, or parents and teachers exchange photographs against the child’s will. As a result, these children try to avoid situations where their parents and teachers meet, which they perceive as unpleasant and threatening. In some cases, such meetings are even a source of fear. Other children, however, unquestioningly accept parent-teacher meetings and the role they themselves are assigned. Yet in these situations they sometimes feel incapacitated and powerless. From the perspective of many children, an educational partnership is therefore not seen as ideal, when all participants – teachers, parents, students – come together as equals, work closely together and discuss all manner of topics. The findings point to a range of ambivalent feelings instead. Children, moreover, are not the only ones who feel ambivalent, as other studies and publications have shown, including those released as part of this research project. Teachers, too, struggle to fulfill their role as school representatives – i.e. to teach, evaluate and, especially in the German context, recommend the best type of secondary school – while also interacting with parents and children as trusting, equal partners. Like children, parents exhibit considerable diversity in terms of how much they want to – or an – get involved in educational institutions. Against this background, we feel it is crucial to take a second look at the idealized concept of educational partnerships – an ideal very present in the educational and policy fields in many countries – and to consider it from a much broader viewpoint. We want to use this study to stimulate discussion about alternative forms, possibilities and goals when it comes to cooperation between parents, teachers and children. All levels – schools, educational administrators and policymakers – should develop and test a variety of cooperative methods. Moreover, they should do more to involve children in shaping the family-school relationship. To that end, student representatives should be systematically queried and included right from the start. Another key aspect is that the ambivalent feelings outlined above need to be acknowledged and considered. So, too, should the power structures and inequalities among adults and children, parents and educational professionals, and families from different social backgrounds. Ultimately, that is the only way to pinpoint and address the limits and risks of cooperation in its various forms, especially as it pertains to the educational opportunities and constraints certain children face. This is an important, challenging task which everyone involved must address. It can only be successfully undertaken if the necessary framework conditions are discussed – i.e. the time, personnel, training and settings required for effectively shaping the family-school relationship – and if adequate resources are made available

Neural hypersensitivity to pleasant touch in women remitted from anorexia nervosa.

Interoception, or the sensing and integration of bodily state signals, has been implicated in anorexia nervosa (AN), given that the hallmark symptoms involve food restriction and body image disturbance. Here we focus on brain response to the anticipation and experience of affective interoceptive stimuli. Women remitted from AN (RAN; N = 18) and healthy comparison women (CW; N = 26) underwent a pleasant affective touch paradigm consisting of gentle strokes with a soft brush administered to the forearm or palm during functional neuroimaging. RAN had a lower brain response relative to CW during anticipation of touch, but a greater response when experiencing touch in the right ventral mid-insula. In RAN, this reduced anticipatory response was associated with higher levels of harm avoidance. Exploratory analyses in RAN also suggested that lower response during touch anticipation was associated with greater body dissatisfaction and higher perceived touch intensity ratings. This reduced responsivity to the anticipation of pleasant affective interoceptive stimuli in association with higher harm avoidance, along with an elevated response to the experience of touch, suggests an impaired ability in AN to predict and interpret incoming physiological stimuli. Impaired interoception may thus impact one's sense of self, thereby supporting observations of disturbed body image and avoidance of affective and social stimuli. Therapeutic approaches that help AN to better anticipate and interpret salient affective stimuli or improve tolerance of interoceptive experiences may be an important addition to current interventions

Impact of the Histidine‐Containing Phosphocarrier Protein HPr on Carbon Metabolism and Virulence in Staphylococcus aureus

Carbon catabolite repression (CCR) is a common mechanism pathogenic bacteria use to link central metabolism with virulence factor synthesis. In gram‐positive bacteria, catabolite control protein A (CcpA) and the histidine‐containing phosphocarrier protein HPr (encoded by ptsH) are the predominant mediators of CCR. In addition to modulating CcpA activity, HPr is essential for glucose import via the phosphotransferase system. While the regulatory functions of CcpA in Staphylococcus aureus are largely known, little is known about the function of HPr in CCR and infectivity. To address this knowledge gap, ptsH mutants were created in S. aureus that either lack the open reading frame or harbor a ptsH variant carrying a thymidine to guanosine mutation at position 136, and the effects of these mutations on growth and metabolism were assessed. Inactivation of ptsH altered bacterial physiology and decreased the ability of S. aureus to form a biofilm and cause infections in mice. These data demonstrate that HPr affects central metabolism and virulence in S. aureus independent of its influence on CcpA regulation

Interventions infirmières favorisant l'adhérence des parents à la vaccination de leurs enfants contre la rougeole dans le domaine de la santé publique: revue de littérature

La thématique de ce travail de Bachelor repose sur les interventions des soignants afin d'améliorer la couverture vaccinale contre la rougeole. But : Déterminer les interventions infirmières permettant de favoriser l’adhérence des parents à la vaccination contre la rougeole et augmenter la couverture vaccinale

Fosmetpantotenate Randomized Controlled Trial in Pantothenate Kinase–Associated Neurodegeneration

Fosmetpantotenate; Randomized controlled trialFosmetpantotenato; Ensayo controlado aleatorizadoFosmetpantotenat; Assaig controlat aleatoritzatBackground Pantothenate kinase–associated neurodegeneration (PKAN) currently has no approved treatments. Objectives The Fosmetpantotenate Replacement Therapy pivotal trial examined whether treatment with fosmetpantotenate improves PKAN symptoms and stabilizes disease progression. Methods This randomized, double-blind, placebo-controlled, multicenter study evaluated fosmetpantotenate, 300 mg oral dose three times daily, versus placebo over a 24-week double-blind period. Patients with pathogenic variants of PANK2, aged 6 to 65 years, with a score ≥6 on the PKAN-Activities of Daily Living (PKAN-ADL) scale were enrolled. Patients were randomized to active (fosmetpantotenate) or placebo treatment, stratified by weight and age. The primary efficacy endpoint was change from baseline at week 24 in PKAN-ADL. Results Between July 23, 2017, and December 18, 2018, 84 patients were randomized (fosmetpantotenate: n = 41; placebo: n = 43); all 84 patients were included in the analyses. Six patients in the placebo group discontinued treatment; two had worsening dystonia, two had poor compliance, and two died of PKAN-related complications (aspiration during feeding and disease progression with respiratory failure, respectively). Fosmetpantotenate and placebo group PKAN-ADL mean (standard deviation) scores were 28.2 (11.4) and 27.4 (11.5) at baseline, respectively, and were 26.9 (12.5) and 24.5 (11.8) at week 24, respectively. The difference in least square mean (95% confidence interval) at week 24 between fosmetpantotenate and placebo was −0.09 (−1.69 to 1.51; P = 0.9115). The overall incidence of treatment-emergent serious adverse events was similar in the fosmetpantotenate (8/41; 19.5%) and placebo (6/43; 14.0%) groups. Conclusions Treatment with fosmetpantotenate was safe but did not improve function assessed by the PKAN-ADL in patients with PKAN.The FORT trial was supported by Retrophin, Inc

Propranolol treatment of infantile hemangioma endothelial cells: A molecular analysis

Infantile hemangiomas (IHs) are non-malignant, largely cutaneous vascular tumors affecting approximately 5–10% of children to varying degrees. During the first year of life, these tumors are strongly proliferative, reaching an average size ranging from 2 to 20 cm. These lesions subsequently stabilize, undergo a spontaneous slow involution and are fully regressed by 5 to 10 years of age. Systemic treatment of infants with the non-selective β-adrenergic receptor blocker, propranolol, has demonstrated remarkable efficacy in reducing the size and appearance of IHs. However, the mechanism by which this occurs is largely unknown. In this study, we sought to understand the molecular mechanisms underlying the effectiveness of β blocker treatment in IHs. Our data reveal that propranolol treatment of IH endothelial cells, as well as a panel of normal primary endothelial cells, blocks endothelial cell proliferation, migration, and formation of the actin cytoskeleton coincident with alterations in vascular endothelial growth factor receptor-2 (VEGFR-2), p38 and cofilin signaling. Moreover, propranolol induces major alterations in the protein levels of key cyclins and cyclin-dependent kinase inhibitors, and modulates global gene expression patterns with a particular affect on genes involved in lipid/sterol metabolism, cell cycle regulation, angiogenesis and ubiquitination. Interestingly, the effects of propranolol were endothelial cell-type independent, affecting the properties of IH endothelial cells at similar levels to that observed in neonatal dermal microvascular and coronary artery endothelial cells. This data suggests that while propranolol markedly inhibits hemangioma and normal endothelial cell function, its lack of endothelial cell specificity hints that the efficacy of this drug in the treatment of IHs may be more complex than simply blockage of endothelial function as previously believed

Expression of different L1 isoforms of Mastomys natalensis papillomavirus as mechanism to circumvent adaptive immunity

Although many high-risk mucosal and cutaneous human papillomaviruses (HPVs) theoretically have the potential to synthesize L1 isoforms differing in length, previous seroepidemiological studies only focused on the short L1 variants, co-assembling with L2 to infectious virions. Using the multimammate mouse Mastomys coucha as preclinical model, this is the first study demonstrating seroconversion against different L1 isoforms during the natural course of papillomavirus infection. Intriguingly, positivity with the cutaneous MnPV was accompanied by a strong seroresponse against a longer L1 isoform, but to our surprise, the raised antibodies were non-neutralizing. Only after a delay of around 4 months, protecting antibodies against the short L1 appeared, enabling the virus to successfully establish an infection. This argues for a novel humoral immune escape mechanism that may also have important implications on the interpretation of epidemiological data in terms of seropositivity and protection of PV infections in general.Fil: Fu, Yingying. German Cancer Research Center; AlemaniaFil: Cao, Rui. German Cancer Research Center; AlemaniaFil: Schäfer, Miriam. German Cancer Research Center; AlemaniaFil: Stephan, Sonja. German Cancer Research Center; AlemaniaFil: Braspenning Wesch, Ilona. German Cancer Research Center; AlemaniaFil: Schmitt, Laura. German Cancer Research Center; AlemaniaFil: Bischoff, Ralf. German Cancer Research Center; AlemaniaFil: Müller, Martin. German Cancer Research Center; AlemaniaFil: Schäfer, Kai. German Cancer Research Center; AlemaniaFil: Vinzon, Sabrina Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Rösl, Frank. German Cancer Research Center; AlemaniaFil: Hasche, Daniel. German Cancer Research Center ; Alemani

MADNESS: A Multiresolution, Adaptive Numerical Environment for Scientific Simulation

MADNESS (multiresolution adaptive numerical environment for scientific simulation) is a high-level software environment for solving integral and differential equations in many dimensions that uses adaptive and fast harmonic analysis methods with guaranteed precision based on multiresolution analysis and separated representations. Underpinning the numerical capabilities is a powerful petascale parallel programming environment that aims to increase both programmer productivity and code scalability. This paper describes the features and capabilities of MADNESS and briefly discusses some current applications in chemistry and several areas of physics

Selective inhibitors of the PSEN1–gamma-secretase complex

Clinical development of γ-secretases, a family of intramembrane cleaving proteases, as therapeutic targets for a variety of disorders including cancer and Alzheimer’s disease was aborted because of serious mechanism-based side effects in the phase III trials of unselective inhibitors. Selective inhibition of specific γ-secretase complexes, containing either PSEN1 or PSEN2 as the catalytic subunit and APH1A or APH1B as supporting subunits, does provide a feasible therapeutic window in preclinical models of these disorders. We explore here the pharmacophoric features required for PSEN1 versus PSEN2 selective inhibition. We synthesized a series of brain penetrant 2-azabicyclo[2,2,2]octane sulfonamides and identified a compound with low nanomolar potency and high selectivity (>250-fold) toward the PSEN1–APH1B subcomplex versus PSEN2 subcomplexes. We used modeling and site-directed mutagenesis to identify critical amino acids along the entry part of this inhibitor into the catalytic site of PSEN1. Specific targeting one of the different γ-secretase complexes might provide safer drugs in the future