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The purpose of this paper is to consider the following two notions; (1) that the use of 'informal education pedagogies' within teaching and learning in the 'academy' can both support the learning process within the 'classroom' but also transcend to society via students; and (2) that synergies exist between informal education and social pedagogical concepts. The discussions are situated from the perspective of an experienced practitioner and academic who is currently teaching youth related degree courses within a Higher Education Institution. This experiential learning has informed knowledge acquisition, understanding and skills application from professional practice to the teaching environment. An experiential learning perspective will be the primary method adopted; the value of this paper lies in its potential to re-affirm that degree courses which embed a 'practice the practice' approach in their teaching methodology support the embedding of core values of the said discipline. The paper argues that the ethically value-based principles and practice of informal education pedagogy, and social pedagogy, are relevant for the current and post COVID-19 pandemic environment.

Myelofibrosis is a chronic myeloproliferative disorder characterized by bone marrow fibrosis, splenomegaly, anemia, and constitutional symptoms, with a median survival of ≈6 years from diagnosis. While currently approved Janus kinase (JAK) inhibitors (ruxolitinib, fedratinib) improve splenomegaly and symptoms, most can exacerbate myelofibrosis‐related anemia, a negative prognostic factor for survival. Momelotinib is a novel JAK1/JAK2/activin A receptor type 1 (ACVR1) inhibitor approved in the US, European Union, and the UK and is the first JAK inhibitor indicated specifically for patients with myelofibrosis with anemia. Momelotinib not only addresses the splenomegaly and symptoms associated with myelofibrosis by suppressing the hyperactive JAK–STAT (signal transducer and activator of transcription) pathway but also improves anemia and reduces transfusion dependency through ACVR1 inhibition. The recommended dose of momelotinib is 200 mg orally once daily, which was established after review of safety, efficacy, pharmacokinetic, and pharmacodynamic data. Momelotinib is metabolized primarily by CYP3A4 and excreted as metabolites in feces and urine. Steady‐state maximum concentration is 479 ng/mL (CV%, 61%), with a mean AUCtau of 3288 ng.h/mL (CV%, 60%); its major metabolite, M21, is active (≈40% of pharmacological activity of parent), with a metabolite‐to‐parent AUC ratio of 1.4–2.1. This review describes momelotinib's mechanism of action, detailing how the JAK–STAT pathway is involved in myelofibrosis pathogenesis and ACVR1 inhibition decreases hepcidin, leading to improved erythropoiesis. Additionally, it summarizes the pivotal studies and data that informed the recommended dosage and risk/benefit assessment. [ABSTRACT FROM AUTHOR]

Understandings of disability are situated within social, political and economic circumstances. Internationally, medical conceptualisations of disability prevail, influencing policy and practice, creating a discourse which encourages categorisation, diagnosis and prescribed ways of understanding behaviour. This body of knowledge has a profound influence, providing powerful explanatory models of disability. Such discourse excludes other ways of knowing, with little attention paid to competences and the construction of worlds especially from the perspectives of disabled children themselves. This article draws upon a small number of UK qualitative studies which have examined disabled child abuse and included the experiences of disabled children. These studies have highlighted how medicalised notions of disability have led to both medicalised and psychiatrised responses to abuse, which have ill-served disabled children. It could be argued that medicalisation has led to disabled children being labelled as either 'too disabled' to be abused or 'not disabled enough' to receive an appropriate response which meets their needs; they are also sometimes regarded as showing signs of mental ill health when such signs are more likely to be an understandable manifestation of the trauma of abuse. Evidence collected indicate that much can be learnt from understanding the construction of disabled childhoods and how our current limited exploration of this affects how society prevents, identifies and responds to disabled child abuse and associated trauma. Drawing upon disabled children's recommendations to 'see me, hear me and understand me', this article will argue that in order to protect disabled children and support them to recover from abuse, we need to move away from a tick-box culture of medicalising, categorising, psychiatrising and 'othering' to a greater understanding of disabled children's worlds, and to a rights-based model of disabled child protection whereby we challenge the increased barriers to support faced by disabled children who have experienced abuse.

Momelotinib—approved for treatment of myelofibrosis in adults with anemia—and its major active metabolite, M21, were assessed as drug–drug interaction (DDI) victims with a strong cytochrome P450 (CYP) 3A4 inhibitor (multiple‐dose ritonavir), an organic anion transporting polypeptide (OATP) 1B1/1B3 inhibitor (single‐dose rifampin), and a strong CYP3A4 inducer (multiple‐dose rifampin). Momelotinib DDI perpetrator potential (multiple‐dose) was evaluated with CYP3A4 and breast cancer resistance protein (BCRP) substrates (midazolam and rosuvastatin, respectively). DDI was assessed from changes in maximum plasma concentration (Cmax), area under the concentration–time curve (AUC), time to reach Cmax, and half‐life. The increase in momelotinib (23% Cmax, 14% AUC) or M21 (30% Cmax, 24% AUC) exposure with ritonavir coadministration was not clinically relevant. A moderate increase in momelotinib (40% Cmax, 57% AUC) and minimal change in M21 was observed with single‐dose rifampin. A moderate decrease in momelotinib (29% Cmax, 46% AUC) and increase in M21 (31% Cmax, 15% AUC) were observed with multiple‐dose rifampin compared with single‐dose rifampin. Due to potentially counteracting effects of OATP1B1/1B3 inhibition and CYP3A4 induction, multiple‐dose rifampin did not significantly change momelotinib pharmacokinetics compared with momelotinib alone (Cmax no change, 15% AUC decrease). Momelotinib did not alter the pharmacokinetics of midazolam (8% Cmax, 16% AUC decreases) or 1′‐hydroxymidazolam (14% Cmax, 16% AUC decreases) but increased rosuvastatin Cmax by 220% and AUC by 170%. Safety findings were mild in this short‐term study in healthy volunteers. This analysis suggests that momelotinib interactions with OATP1B1/1B3 inhibitors and BCRP substrates may warrant monitoring for adverse reactions or dose adjustments. [ABSTRACT FROM AUTHOR]

Through the creation of safe spaces in which to explore and challenge dominant negative views of disabled children and young people, this co‐written paper presents unique insight into the meaning and impact upon disabled young people's lives of medical lenses and deficit models of disability. Bodies of work and dominant debates in medical sociology, disability studies and childhood studies have so far largely overlooked the experiences and positioning of disabled children and young people and have rarely involved them in the development or discussion of theory. Drawing on empirical data, and through a series of creative, reflective workshops with a UK‐based disabled young researchers' collective (RIP:STARS), this paper discusses areas of theoretical importance identified by the disabled young researcher collective—the validation of their lives, negotiation of their identity and acceptance in society. The implications, and possibilities, of platforming disabled children and young people's voices in theoretical debates are deliberated and are achieved through the yielding of privileged academic voice and the development of a symbiotic, genuine partnership which resonates with disabled young people and recognises them as experts in their own lives. [ABSTRACT FROM AUTHOR]

In 2009 the National Society for the Protection of Cruelty to Children published "Partner Exploitation and Violence in Teenage Intimate Relationships". This publication reports on the first major study in the United Kingdom to systematically document the incidence rates and dynamics of intimate partner violence in the lives of young people. It also highlights the UK research communities' lack of attention to the issue of young people and partner violence; much of what is known about young people's experiences of violence within their intimate relationships has been informed by research undertaken in the USA. In this article we contribute to the growing body of research in the United Kingdom and present findings from a qualitative study that explored pregnant teenagers and young mothers' experience of power, control and domestic violence in their familial and intimate relationships. Our study highlights the complexities and contradictions relating to the notion of family support, with young women respondents sometimes identifying this "support" as controlling. Our findings also show how young mothers, like older adult women, are subject to a range of violent behaviours in their intimate relationships. We conclude that any attempt to minimise the "risks" this group face needs to recognise how familial and intimate relationships can negatively impact on the health and well-being of pregnant teenagers, of young mothers and that of their child/children.

Molibresib (GSK525762) is an investigational orally bioavailable small‐molecule bromodomain and extraterminal (BET) protein inhibitor for the treatment of advanced solid tumors. In the first‐time‐in‐human BET115521 study of molibresib in patients with solid tumors, thrombocytopenia was the most frequent treatment‐related adverse event (AE), QT prolongation was an AE of special interest based on preclinical signals, and gastrointestinal (GI) AEs (nausea, vomiting, diarrhea, and dysgeusia) were often observed. The aims of this analysis were the following: (i) develop a population pharmacokinetic (PK)/pharmacodynamic (PD) model capable of predicting platelet time courses in individual patients after administration of molibresib and identify covariates of clinical interest; (ii) evaluate the effects of molibresib (and/or its two active metabolites [GSK3529246]) exposure on cardiac repolarization by applying a systematic modeling approach using high‐quality, intensive, PK time‐matched 12‐lead electrocardiogram measurements; (iii) evaluate the exposure–response (ER) relationship between molibresib and/or GSK3529246 exposures and the occurrence of Grade 2 or higher GI AEs. Overall, the PK/PD model (including a maximal drug effect model and molibresib concentration) adequately described platelet counts following molibresib treatment and was used to simulate the impact of molibresib dosing on thrombocytopenia at different doses and regimens. ER analyses showed no clinically meaningful QT interval prolongation with molibresib at up to 100 mg q.d., and no strong correlation between molibresib exposure and the occurrence of Grade 2 or higher GI AEs. The models described here can aid dosing/schedule and drug combination strategies and may support a thorough QT study waiver request for molibresib. [ABSTRACT FROM AUTHOR]