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# Background Many people with disabilities in low-income settings, such as Sierra Leone, do not have access to the assistive technology (AT) they need, yet research to measure and address this issue remains limited. This paper presents a case study of the Assistive Technology 2030 (AT2030) funded Country Investment project in Sierra Leone. The research explored the nature and strength of the AT stakeholder network in Sierra Leone over the course of one year, presenting a snapshot of the network before and after a targeted systems level investment. # Methods Mixed-method surveys were distributed via the Qualtrics software twice, in December 2021 and September 2022 to n=20 and n=16 participants (respectively). Qualitative data was analyzed thematically, while quantitative data was analyzed with the NodeXL software and MS Excel to generate descriptive statistics, visualizations, and specific metrics related to indegree, betweenness and closeness centrality of organizations grouped by type. # Results Findings suggest the one-year intervention did stimulate change within the AT network in Sierra Leone, increasing the number of connections within the AT network and strengthening existing relationships within the network. Findings are also consistent with existing data suggesting cost is a key barrier to AT access for both organizations providing AT and people with disabilities to obtain AT. # Conclusion While this paper is the first to demonstrate that a targeted investment in AT systems and policies at the national level can have a resulting impact on the nature and strength of the AT, it only measures outcomes at one-year after investment. Further longitudinal impact evaluation would be desirable. Nonetheless, the results support the potential for systemic investments which leverage inter-organizational relationships and prioritize financial accessibility of AT, as one means of contributing towards increased access to AT for all, particularly in low-income settings.

Introduction Assistive technology (AT) is important for the achievement of the sustainable development goals (SDGs) for persons with disabilities (PWD). Increasingly, studies suggest a significant gap between the need for and demand for and provisions of AT for PWD in low-income and middle-income settings. Evidence from high income countries highlights the importance of robust AT policies to the achievement of the recommendations of the World Health Assembly on AT. In Malawi, there is no standalone AT policy. The objectives of the Assistive Product List Implementation Creating Enablement of inclusive SDGs (APPLICABLE) project, are to propose and facilitate the development of a framework for creating effective national AT policy and specify a system capable of implementing such policies in low-income countries such as Malawi.Method and analysis We propose an action research process with stakeholders in AT in Malawi. APPLICABLE will adopt an action research paradigm, through developing a shared research agenda with stakeholders and including users of AT. This involves the formation of an Action Research Group that will specify the priorities for practice—and policy-based evidence, in order to facilitate the development of contextually realistic and achievable policy aspirations on AT in Malawi and provide system strengthening recommendations that will ensure that the policy is implementable for their realisation. We will undertake an evaluation of this policy by measuring supply and support for specific AT prior to, and following the implementation of the policy recommendations.Ethics and dissemination The study protocol was approved by Maynooth University Research Ethics Committee (SRESC-2019-2378566) and University of Malawi Research Ethics Committee (P.01/20/10). Findings from the study will be disseminated by publication in peer-reviewed journals, presentations to stakeholders in Malawi, Ireland and international audiences at international conferences.

To aid preclinical development of novel therapeutics for myeloma, an in vivo model which recapitulates the human condition is required. An important feature of such a model is the interaction of myeloma cells with the bone marrow microenvironment, as this interaction modulates tumour activity and protects against drug-induced apoptosis. Therefore NOD/SCIDγc(null) mice were injected intra-tibially with luciferase-tagged myeloma cells. Disease progression was monitored by weekly bioluminescent imaging (BLI) and measurement of paraprotein levels. Results were compared with magnetic resonance imaging (MRI) and histology. Assessment of model suitability for preclinical drug testing was investigated using bortezomib, melphalan and two novel agents. Cells engrafted at week 3, with a significant increase in BLI radiance occurring between weeks 5 and 7. This was accompanied by an increase in paraprotein secretion, MRI-derived tumour volume and CD138 positive cells within the bone marrow. Treatment with known anti-myeloma agents or novel agents significantly attenuated the increase in all disease markers. In addition, intra-tibial implantation of primary patient plasma cells resulted in development of myeloma within bone marrow. In conclusion, using both myeloma cell lines and primary patient cells, we have developed a model which recapitulates human myeloma by ensuring the key interaction of tumour cells with the microenvironment.

Background Assistive technology is central to the realization of the rights of persons with disabilities. However, there remains limited access to assistive technology throughout much of the world, with particularly poor access in lower- and middle-income countries. Evaluating stakeholder engagement in assistive technology networks has been used as a successful strategy to understand and address gaps in the assistive technology ecosystem. Objective The objective of this research was to provide an overview of the Kenyan Assistive Technology Ecosystem, including available assistive products and related services, and an understanding of the nature and strength of relationships between stakeholders Methods In this study, we employed an online qualitative stakeholder survey (2021) with representatives of organizations involved in assistive technology in Kenya. Results The assistive technology network in Kenya is distributed, with Government Ministries and Agencies and Organizations of persons with disabilities central to the network. The strength of relationships is concentrated on awareness and communication, with fewer organizations actively collaborating. Innovation training organizations are not yet well integrated into the network. Conclusions Improving access to assistive technology in Kenya will benefit from greater collaboration amongst all assistive technology stakeholders.

Summary: Studies have reported increased intestinal permeability in multiple sclerosis (MS) patients and its mouse model experimental autoimmune encephalomyelitis (EAE). However, the mechanisms driving increased intestinal permeability that in turn exacerbate neuroinflammation during EAE remain unclear. Here we showed that vancomycin preserved the integrity of the intestinal barrier, while also suppressing gut trypsin activity, enhancing the relative abundance of specific Lactobacilli and ameliorating disease during EAE. Furthermore, Lactobacilli enriched in the gut of vancomycin-treated EAE mice at day 3 post immunization negatively correlated with gut trypsin activity and EAE severity. In untreated EAE mice, we observed increased intestinal permeability and increased intestinal protease activated receptor 2 (PAR2) expression at day 3 post immunization. Prior studies have shown that trypsin increases intestinal permeability by activating PAR2. Our results suggest that the interaction between intestinal PAR2 and trypsin may be a key modulator of intestinal permeability and disease severity during EAE.

Abstract Background The gut microbiome plays an important role in autoimmunity including multiple sclerosis and its mouse model called experimental autoimmune encephalomyelitis (EAE). Prior studies have demonstrated that the multiple sclerosis gut microbiota can contribute to disease, hence making it a potential therapeutic target. In addition, antibiotic treatment has been shown to ameliorate disease in the EAE mouse model of multiple sclerosis. Yet, to this date, the mechanisms mediating these antibiotic effects are not understood. Furthermore, there is no consensus on the gut-derived bacterial strains that drive neuroinflammation in multiple sclerosis. Results Here, we characterized the gut microbiome of untreated and vancomycin-treated EAE mice over time to identify bacteria with neuroimmunomodulatory potential. We observed alterations in the gut microbiota composition following EAE induction. We found that vancomycin treatment ameliorates EAE, and that this protective effect is mediated via the microbiota. Notably, we observed increased abundance of bacteria known to be strong inducers of regulatory T cells, including members of Clostridium clusters XIVa and XVIII in vancomycin-treated mice during the presymptomatic phase of EAE, as well as at disease peak. We identified 50 bacterial taxa that correlate with EAE severity. Interestingly, several of these taxa exist in the human gut, and some of them have been implicated in multiple sclerosis including Anaerotruncus colihominis, a butyrate producer, which had a positive correlation with disease severity. We found that Anaerotruncus colihominis ameliorates EAE, and this is associated with induction of RORγt+ regulatory T cells in the mesenteric lymph nodes. Conclusions We identified vancomycin as a potent modulator of the gut-brain axis by promoting the proliferation of bacterial species that induce regulatory T cells. In addition, our findings reveal 50 gut commensals as regulator of the gut-brain axis that can be used to further characterize pathogenic and beneficial host-microbiota interactions in multiple sclerosis patients. Our findings suggest that elevated Anaerotruncus colihominis in multiple sclerosis patients may represent a protective mechanism associated with recovery from the disease. Video Abstract

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has impacted all segments of society, but it has posed particular challenges for the inclusion of persons with disabilities, those with chronic illness and older people regarding their participation in daily life. These groups often benefit from assistive technology (AT) and so it is important to understand how use of AT may be affected by or may help to mitigate the impacts of COVID-19. ObjectiveThe objectives of this study were to explore the how AT use and provision have been affected during the initial stages of the COVID-19 pandemic, and how AT policies and systems may be made more resilient based on lessons learned during this global crisis. MethodsThis study was a rapid, international online qualitative survey in the 6 United Nations (UN) languages (English, French, Spanish, Russian, Arabic, Mandarin Chinese) facilitated by extant World Health Organization (WHO) and International Disability Alliance networks. Themes and subthems of the qualitative responses were identified using Braun and Clarke’s 6-phase analysis. ResultsFour primary themes were identified in in the data: Disruption of Services, Insufficient Emergency Preparedness, Limitations in Existing Technology, and Inadequate Policies and Systems. Subthemes were identified within each theme, including subthemes related to developing resilience in AT systems, based on learning from the pandemic. ConclusionCOVID-19 has disrupted the delivery of AT services, primarily due to infection control measures resulting in lack of provider availability and diminished one-to-one services. This study identified a need for stronger user-centred development of funding policies and infrastructures that are more sustainable and resilient, best practices for remote service delivery, robust and accessible tools and systems, and increased capacity of clients, caregivers, and clinicians to respond to pandemic and other crisis situations.

Assistive technologies are critical to supporting the participation and engagement of persons with disabilities and others who experience functional difficulties in daily life. Assistive products have been demonstrated to be related to the achievement of the Sustainable Development Goals (SDGs); however, no previous research has explored the relationship between assistive technology (AT) and the SDGs from the perspective of stakeholder organisations working in the field of AT provision. In this study, we evaluated the relevance of AT and the SDGs to achieving the organisational missions of key stakeholders in AT ecosystem in Malawi. Key stakeholders (n = 36) in the AT field in Malawi were asked to rate the relevance of AT to achieving their organisational missions, and the relevance of AT to each of the 17 SDGs on a 5-point Likert scale. Stakeholders who participated were engaged in consultative meetings with the government and an action research team as part of a larger policy development project, and represented ministries and government agencies, organisations of persons with disabilities, and local and international non-governmental organisations. AT was rated as being relevant to all of the SDGs, albeit to varying degrees, and not surprisingly to achieving AT stakeholders’ organisational missions. The cross-cutting nature of the relevance of AT underscores the importance of cross-ministerial cooperation and shared leadership in provision AT.

Background Assistive technologies promote participation and quality of life for people with disabilities and other functional limitations. There is a global call to develop and implement policies to improve access to assistive technologies. In response, a stakeholder led initiative in Malawi is working towards the development of such a policy. Objective The objective of this study was to assess the existing network of stakeholders, and the strength of relationship between organizations who deliver assistive products and related services. Method We conducted a survey-based network analysis of assistive technology stakeholder organizations in Malawi. Results Stakeholders (n = 19) reported a range of connections, from no awareness to collaboration with organizations within the assistive technology network. No single organization or government ministry was most central to the network. International NGOs were less central to the network than local organizations for disabled people, service providers, and ministries. Conclusion The assistive technology stakeholder network in Malawi is distributed, with a range of responsibility across a variety of stakeholders, including three government ministries. An effective assistive technology policy must engage all stakeholders and may benefit from a collective leadership approach that spans the inter-sectoral need for a cohesive assistive technology system.

Abstract Background Equity and inclusion are important principles in policy development and implementation. The aim of this study is to explore the extent to which equity and inclusion were considered in the development of Malawi’s National Disability Mainstreaming Strategy and Implementation Plan. Methods We applied an analytical methodology to review the Malawi’s National Disability Mainstreaming Strategy and Implementation Plan using the EquIPP (Equity and Inclusion in Policy Processes) tool. The EquIPP tool assesses 17 Key Actions to explore the extent of equity and inclusion. Results The development of the Malawi National Disability Mainstreaming Strategy and Implementation Plan was informed by a desire to promote the rights, opportunities and wellbeing of persons with disability in Malawi. The majority (58%) of the Key Actions received a rating of three, indicating evidence of clear, but incomplete or only partial engagement of persons with disabilities in the policy process. Three (18%) of the Key Actions received a rating of four indicating that all reasonable steps to engage in the policy development process were observed. Four (23%) of the Key Actions received a score five indicating a reference to Key Action in the core documents in the policy development process. Conclusions The development of disability policies and associated implementation strategies requires equitable and inclusive processes that consider input from all stakeholders especially those whose wellbeing depend on such policies. It is pivotal for government and organisations in the process of policy or strategy development and implementation, to involve stakeholders in a virtuous process of co-production – co-implementation – co-evaluation, which may strengthen both the sense of inclusion and the effectiveness of the policy life-cycle.

Diamond-Blackfan anemia (DBA) is an inherited bone marrow failure disorder in which pure red blood cell aplasia is associated with physical malformations and a predisposition to cancer. Twentyfive percent of patients with DBA have mutations in a gene encoding ribosomal protein S19 (RPS19). Our previous proof-of-concept studies demonstrated that DBA phenotype could be successfully treated using lentiviral vectors in Rps19-deficient DBA mice. In our present study, we developed a clinically applicable single gene, self-inactivating lentiviral vector, containing the human RPS19 cDNA driven by the human elongation factor 1a short promoter, which can be used for clinical gene therapy development for RPS19-deficient DBA. We examined the efficacy and safety of the vector in a Rps19-deficient DBA mouse model and in human primary RPS19-deficient CD34+ cord blood cells. We observed that transduced Rps19-deficient bone marrow cells could reconstitute mice long-term and rescue the bone marrow failure and severe anemia observed in Rps19-deficient mice, with a low risk of mutagenesis and a highly polyclonal insertion site pattern. More importantly, the vector can also rescue impaired erythroid differentiation in human primary RPS19-deficient CD34+ cord blood hematopoietic stem cells. Collectively, our results demonstrate the efficacy and safety of using a clinically applicable lentiviral vector for the successful treatment of Rps19-deficient DBA in a mouse model and in human primary CD34+ cord blood cells. These findings show that this vector can be used to develop clinical gene therapy for RPS19-deficient DBA patients.

Importance: Powered wheelchairs provide independence for people with mobility impairments; however, current training practices may not meet the needs of those with cognitive impairments. Shared-control teleoperation may have utility in a clinical setting when developing training suited to this population., Objective: To explore the clinical utility of a shared-control teleoperation device for powered wheelchair assessment and training., Design: In this qualitative study, we used two sequential semistructured interviews conducted a minimum of 2 wk apart. Thematic analyses were used with member checking, reflexive journaling, and triangulation of researchers to establish trustworthiness of the data., Setting: Rehabilitation center and residential care and community settings., Participants: Using purposive sampling, we recruited occupational therapists and physical therapists who were mostly female and who had a range of practice experience., Results: Fifteen participants were interviewed, and two primary themes were identified: (1) "A big enabler" described how shared control provides opportunities to train people who may otherwise be denied powered mobility, and (2) "changing the learner experience" described how shared control may promote success in skill development through an alternative learning experience., Conclusions and Relevance: Shared-control technology may have the potential to broaden the scope of therapeutic intervention by reducing risk to the driver and others in the environment and by facilitating alternative training approaches., What This Article Adds: Technological advances that allow more control over a powered wheelchair by a clinician, known as shared control, may provide learning opportunities for people who are otherwise denied access to powered mobility. Shared control may also allow the use of new instructional techniques, increase safety in the training process, and reduce anxiety associated with learning., (Copyright © 2019 by the American Occupational Therapy Association, Inc.)