Research priorities for mitochondrial disorders: Current landscape and patient and professional views

Primary mitochondrial disorders encompass a wide range of clinical presentations and a spectrum of severity. They currently lack effective disease-modifying therapies and have a high mortality and morbidity rate. It is therefore essential to know that competitively-funded research designed by academics meets core needs of people with mitochondrial disorders and their clinicians. The Priority Setting Partnerships are an established collaborative methodology that brings patients, carers and families, charity representatives and clinicians together to try to establish the most pressing and unanswered research priorities for a particular disease. We developed a web-based questionnaire, requesting all patients affected by primary mitochondrial disease, their carers, and clinicians to pose their research questions. This yielded 709 questions from 147 participants. These were grouped into overarching themes including basic biology, causation, health services, clinical management, social impacts, prognosis, prevention, symptoms, treatment, and psychological impact. Following the removal of 'answered questions' the process resulted in a list of 42 discrete, answerable questions. This was further refined by web-based ranking by the community to 24 questions. These were debated at a face-to-face workshop attended by a diverse range of patients, carers, charity representatives and clinicians to create a definitive 'Top Ten of unanswered research questions for primary mitochondrial disorders'. These Top Ten questions related to understanding biological processes, including triggers of disease onset, mechanisms underlying progression and reasons for differential symptoms between individuals with identical genetic mutations; new treatments; biomarker discovery; psychological support; and optimal management of stroke-like episodes and fatigue

Research priorities for mitochondrial disorders: current landscape and patient and professional views

Primary mitochondrial disorders encompass a wide range of clinical presentations and a spectrum of severity. They currently lack effective disease-modifying therapies and have a high mortality and morbidity rate. It is therefore essential to know that competitively-funded research designed by academics meets core needs of people with mitochondrial disorders and their clinicians. The Priority Setting Partnerships are an established collaborative methodology that brings patients, carers and families, charity representatives and clinicians together to try to establish the most pressing and unanswered research priorities for a particular disease. We developed a web-based questionnaire, requesting all patients affected by primary mitochondrial disease, their carers, and clinicians to pose their research questions. This yielded 709 questions from 147 participants. These were grouped into overarching themes including basic biology, causation, health services, clinical management, social impacts, prognosis, prevention, symptoms, treatment, and psychological impact. Following the removal of ‘answered questions’ the process resulted in a list of 42 discrete, answerable questions. This was further refined by web-based ranking by the community to 24 questions. These were debated at a face-to-face workshop attended by a diverse range of patients, carers, charity representatives and clinicians to create a definitive ‘Top Ten of unanswered research questions for primary mitochondrial disorders’. These Top Ten questions related to understanding biological processes, including triggers of disease onset, mechanisms underlying progression and reasons for differential symptoms between individuals with identical genetic mutations; new treatments; biomarker discovery; psychological support; and optimal management of stroke-like episodes and fatigue

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The Words of the Wise and Polemical Theology*

Multiple studies have explored polemic theology, or the apologetic adaptation of extrabiblical material in Scripture. However, a less-explored potential application is the use of foreign wisdom literature in a section of Proverbs often termed The Words to the Wise [Ones] (Proverbs 22:17-24:22). Among these sayings is Proverbs 23:17-18, which alludes to the idea of a distinctly Israelite afterlife in which all injustice will be set right. This project analyzes the prevalence of this concept in both Proverbs and the ancient Near East and investigates the applicability of polemic theology in this passage

Ngā Kaupapa Wawata me Uara: A narrative review exploring Tiriti o Waitangi-centred population health programmes in Aotearoa New Zealand

Globally, Indigenous Peoples experience widespread health inequities. Treaties provide a potential framework to uphold Indigenous rights and progress health equity. Te Tiriti o Waitangi (Māori language version of the Treaty of Waitangi) established the relationship between Māori, the Indigenous people of Aotearoa (New Zealand), and the British Crown. Grounded in Kaupapa Māori theory, this literature review used an Indigeneity-Grounded Analysis (IGA) policy lens to identify four characteristics of Tiriti-centred population health programmes: whanaungatanga (relationships), pro-equity actions, Te Ao Māori (Māori worldviews), and accountability. Although the evidence-base is emergent, a rights-based approach identifies the centrality of Indigenous self-determination, structural and system transformation, and freedom from discrimination. Indigenous knowledge provides the foundation for treaty-centered policy supportive of Indigenous rights and health equity

Indexed Concatenation Notation: A Novel Way to Summarize Networks and Other Complex Systems

The indexed concatenation notation presented in this paper extends the concept of concatenation in a way similar to the extension of addition to the indexed sum, allowing compact representations of strings, lists, matrices, etc., having internal repetitive or describable structure. In particular, it allows the edge difference set list of any graphical network with a visible pattern to be summarized in an extremely compact and lossless way. Examples highlight the information compression of the technique and showcase its ability to represent complicated, infinite patterns in closed form

Protocol for the Tessa Jowell BRAIN MATRIX Platform Study

INTRODUCTION: Gliomas are the most common primary tumour of the central nervous system (CNS), with an estimated annual incidence of 6.6 per 100 000 individuals in the USA and around 14 deaths per day from brain tumours in the UK. The genomic and biological landscape of brain tumours has been increasingly defined and, since 2016, the WHO classification of tumours of the CNS incorporates molecular data, along with morphology, to define tumour subtypes more accurately. The Tessa Jowell BRAIN MATRIX Platform (TJBM) study aims to create a transformative clinical research infrastructure that leverages UK National Health Service resources to support research that is patient centric and attractive to both academic and commercial investors. METHODS AND ANALYSIS: The TJBM study is a programme of work with the principal purpose to improve the knowledge of glioma and treatment for patients with glioma. The programme includes a platform study and subsequent interventional clinical trials (as separate protocols). The platform study described here is the backbone data-repository of disease, treatment and outcome data from clinical, imaging and pathology data being collected in patients with glioma from secondary care hospitals. The primary outcome measure of the platform is time from biopsy to integrated histological–molecular diagnosis using whole-genome sequencing and epigenomic classification. Secondary outcome measures include those that are process centred, patient centred and framework based. Target recruitment for the study is 1000 patients with interim analyses at 100 and 500 patients. ETHICS AND DISSEMINATION: The study will be performed in accordance with the recommendations guiding physicians in biomedical research involving human subjects, adopted by the 18th World Medical Association General Assembly, Helsinki, Finland and stated in the respective participating countries’ laws governing human research, and Good Clinical Practice. The protocol was initially approved on 18 February 2020 by West Midlands – Edgbaston Research Ethics Committee; the current protocol (v3.0) was approved on 15 June 2022. Participants will be required to provide written informed consent. A meeting will be held after the end of the study to allow discussion of the main results among the collaborators prior to publication. The results of this study will be disseminated through national and international presentations and peer-reviewed publications. Manuscripts will be prepared by the Study Management Group and authorship will be determined by mutual agreement. TRIAL REGISTRATION NUMBER: NCT04274283, 18-Feb-2020; ISRCTN14218060, 03-Feb-2020