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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.

Abstract Background With most mental health problems established during childhood/adolescence, young people must be a key focus of public mental health approaches. Despite the range of factors known to influence mental health, evidence for effective interventions is lacking for this age group. This study aimed to define priorities for future public health intervention-focused research to support youth mental health by engaging with transdisciplinary stakeholder groups. Methods Our coproduction approach involved priority-setting workshops with young people, researchers, practitioners and policy-makers. Each workshop focused on three thematic areas: social connections and relationships; schools and other education settings; and key groups at greater risk of mental ill-health, specifically LGBTQ+ and care-experienced young people. Workshop outputs were synthesized to define research priorities. Results This paper presents the research priorities that were defined through the priority-setting workshops, and our reflections on the coproduction approach to guide future similar activities undertaken by others. Ten priorities for youth public mental health research were defined, covering the following areas: building supportive relationships; whole system approaches; social media; support at times of transition; improving links between different services; development and training for those who support young people; staff mental health; engaging with families; awareness of and access to services; and out-of-school and community settings. Conclusions These research priorities can inform future intervention development to support youth public mental health. Our transdisciplinary approach means the identified research priorities are likely to be relevant to young people’s experiences and needs, and to fit with the needs of those working in practice and policy to support young people.

The extent of how mobile devices, such as smartphones and tablets, are seamlessly incorporated into the personal day-to-day life is not often considered by University instructors. Unfocused incorporation of mobile technologies into the classroom can de-emphasize intended learning objectives if students struggle to use the technology itself or by acting as a distraction. The effective inclusion of mobile technology is not a simple process as the intervention needs to be purposeful and have the potential to improve the student learning environment while working alongside more traditional face-to-face learning. This paper presents a pathway to help instructors address both pedagogical and technological considerations of incorporating mobile learning into the curriculum. The pathway developed through the adaptation of the iPAC framework, feedback from international practitioners and tested with worked examples. In all cases, the instructors' reflective responses to the eight pathway questions indicate a clear structured activity, engaged students and considers equal access, prior experience and contingency planning. This pathway indicates an effective methodology for instructors to assess whether the mobile learning intervention is appropriate and adds value to their teaching. Further external evaluation of the pathway with additional teaching examples will enhance the effectiveness of the methodology.

Abstract Background Patients with generalized myasthenia gravis (MG) often experience debilitating exacerbations, with the possibility of life-threatening respiratory crises requiring hospitalization. Long-term longitudinal studies are needed to understand the burden of MG, including in patients whose disease is refractory to conventional treatment. Methods A retrospective, longitudinal, cohort study was conducted of patients in England aged ≥ 18 years with treatment-refractory or non-refractory MG, using data recorded during 1997–2016 in the Clinical Practice Research Datalink and the Hospital Episode Statistics databases. A control cohort of patients without MG, matched to the patients in the treatment-refractory MG cohort, was also identified. Outcome measures included myasthenic crises, MG exacerbations, MG-related hospitalizations, comorbidities, and all-cause mortality. Descriptive statistics were calculated for the overall MG population. For continuous variables, between-cohort comparisons were made using t tests for normally distributed data and Mann–Whitney U tests for non-normally distributed data. For categorical data, the comparisons were made by chi-squared tests. Differences in clinical outcomes between cohorts were modeled using negative binomial regression. Results A total of 1149 patients with MG were included. Overall, 18.4% of patients experienced myasthenic crises, 24.6% experienced exacerbations, and 38.6% underwent MG-related hospitalizations. Most of these events occurred within 2–3 years of diagnosis. Patients with MG refractory to conventional treatment (n = 66) experienced more exacerbations and MG-related hospitalizations than patients with non-refractory disease (n = 1083). Patients with refractory MG experienced a higher frequency of renal disease and hypertension compared with patients with non-refractory MG, and with matched patients without MG. They were also more likely to have diabetes and congestive heart failure than the matched controls. Rates of all-cause mortality during the follow-up period did not differ between patients with refractory MG and non-refractory MG. Conclusions These results show that conventional treatments for MG are not adequately managing patients’ symptoms and that patients with refractory MG are more likely to experience certain comorbidities than those with non-refractory MG or matched controls without MG. Future research should focus on the impact of newer targeted therapies on long-term clinical outcomes and comorbid conditions.

Abstract Background Rare diseases (RDs) are often complex, serious, chronic and multi-systemic conditions, associated with physical, sensory and intellectual disability. Patients require follow-up management from multiple medical specialists and health and social care professionals involving a high level of integrated care, service coordination and specified care pathways. Methods and objectives This pilot study aimed to explore the best approach for developing national RD care pathways in the Irish healthcare system in the context of a lack of agreed methodology. Irish clinical specialists and patient/lived experience experts were asked to map existing practice against evidence-based clinical practice guidelines (CPGs) and best practice recommendations from the European Reference Networks (ERNs) to develop optimal care pathways. The study focused on the more prevalent, multisystemic rare conditions that require multidisciplinary care, services, supports and therapeutic interventions. Results 29 rare conditions were selected across 18 ERNs, for care pathway development. Multidisciplinary input from multiple specialisms was relevant for all pathways. A high level of engagement was experienced from clinical leads and patient organisations. CPGs were identified for 26 of the conditions. Nurse specialist, Psychology, Medical Social Work and Database Manager roles were deemed essential for all care pathways. Access to the therapeutic Health Service Professionals: Physiotherapy, Occupational Therapy, and Speech and Language Therapy were seen as key requirements for holistic care. Genetic counselling was highlighted as a core discipline in 27 pathways demonstrating the importance of access to Clinical Genetics services for many people with RDs. Conclusions This study proposes a methodology for Irish RD care pathway development, in collaboration with patient/service user advocates. Common RD patient needs and health care professional interventions across all pathways were identified. Key RD stakeholders have endorsed this national care pathway initiative. Future research focused on the implementation of such care pathways is a priority.

Abstract Background While family caregivers provide 70-90% of care for people living in the community and assist with 10-30% of the care in congregate living, most healthcare providers do not meaningfully involve family caregivers as partners in care. Recent research recommends that the healthcare workforce receive competency-based education to identify, assess, support, and partner with family caregivers across the care trajectory. Objective This paper reports a mixed-methods evaluation of a person-centered competency-based education program on Caregiver-Centered Care for the healthcare workforce. Methods This foundational education was designed for all healthcare providers and trainees who work with family caregivers and is offered free online (caregivercare.ca). Healthcare providers from five healthcare settings (primary, acute, home, supportive living, long-term care) and trainees in medicine, nursing, and allied health were recruited via email and social media. We used the Kirkpatrick-Barr health workforce training evaluation framework to evaluate the education program, measuring various healthcare providers’ learner satisfaction with the content (Level 1), pre-post changes in knowledge and confidence when working with family caregivers (Level 2), and changes in behaviors in practice (Level 3). Results Participants were primarily healthcare employees (68.9%) and trainees (21.7%) and represented 5 healthcare settings. Evaluation of the first 161 learners completing the program indicated that on a 5-point Likert scale, the majority were satisfied with the overall quality of the education (Mean(M) = 4.69; SD = .60). Paired T-tests indicated that out of a score of 50, post-education changes in knowledge and confidence to work with family caregivers was significantly higher than pre-education scores (pre M = 38.90, SD = 6.90; post M = 46.60, SD = 4.10; t(150) = − 16.75, p

We report the reversible transformation between a singly stapled dynamic α‐helical peptide and a doubly stapled quasi‐static one through redox‐triggered dithiol/disulfide conversions of a stapling moiety. This process allows the rate of interconversion between the right‐handed (P) and left‐handed (M) α‐helices to be altered by a factor of approximately 103 before and after the transformation. An as‐obtained doubly stapled α‐helical peptide, which is composed of an achiral peptide having an l‐valine carboxylic acid residue at the C‐terminus, a disulfide‐based reversible staple, and a biphenyl‐based fixed staple, adopts an (M)‐rich form as a kinetically trapped state. The (M)‐rich helix was subsequently transformed into the thermodynamically stable (P)‐rich form in 1,1,2,2‐tetrachloroethane with the half‐life time (t1/2) of approximately 44 days at 25 °C. Reduction of the doubly stapled peptide with tri‐n‐butylphosphine in tetrahydrofuran/water (10/1, v/v) produced the corresponding singly stapled dynamic α‐helical peptide bearing two thiol groups at the side chains, which underwent solvent‐induced reversible helicity inversion. The resulting dithiol of the singly stapled peptide could be reoxidized to form the original doubly stapled form using 4,4'‐dithiodipyridine. Furthermore, the P/M interconversion of a doubly stapled peptide with two flexible hydrocarbon‐based staples is considerably more rapid than that with more rigid staples. [ABSTRACT FROM AUTHOR]

In this paper, we are concerned with efficiently solving the sequences of regularized linear least-squares problems associated with employing Tikhonov-type regularization with regularization operators designed to enforce edge recovery. An optimal regularization parameter, which balances the fidelity to the data with the edge-enforcing constraint term, is typically not known a priori. This adds to the total number of regularized linear least-squares problems that must be solved before the final image can be recovered. Therefore, in this paper, we determine effective multigrid preconditioners for these sequences of systems. We focus our approach on the sequences that arise as a result of the edge-preserving method introduced in [S. Gazzola et al., Inverse Problems, 36 (2020), 124004], where we can exploit an interpretation of the regularization term as a diffusion operator; however, our methods are also applicable in other edge-preserving settings, such as iteratively reweighted least-squares problems. Particular attention is paid to the selection of components of the multigrid preconditioner in order to achieve robustness for different ranges of the regularization parameter value. In addition, we present a parameter trimming approach that, when used with the L-curve heuristic, reduces the total number of solves required. We demonstrate our preconditioning and parameter trimming routines on examples in computed tomography and image deblurring. [ABSTRACT FROM AUTHOR]

Clustering is a commonplace problem in many areas of data science, with applications in biology and bioinformatics, understanding chemical structure, image segmentation, building recommender systems, and many more fields. While there are many different clustering variants (based on given distance or graph structure, probability distributions, or data density), we consider here the problem of clustering nodes in a graph, motivated by the problem of aggregating discrete degrees of freedom in multigrid and domain decomposition methods for solving sparse linear systems. Specifically, we consider the challenge of forming balanced clusters in the graph of a sparse matrix for use in algebraic multigrid, although the algorithm has general applicability. Based on an extension of the Bellman--Ford algorithm, we generalize Lloyd's algorithm for partitioning subsets of ℝn to balance the number of nodes in each cluster; this is accompanied by a rebalancing algorithm that reduces the overall energy in the system. The algorithm provides control over the number of clusters and leads to "well centered" partitions of the graph. Theoretical results are provided to establish linear complexity and numerical results in the context of algebraic multigrid highlight the benefits of improved clustering. [ABSTRACT FROM AUTHOR]

The objectives of this research study were to examine local level factors shaping the implementation of a blended pedagogical approach for geospatial- and information-literacy, and to understand implementer satisfaction. As such, we addressed the following research questions: What local-level factors shape the implementation of the blended learning model? and How satisfied are implementers (faculty, administrators and library instructional/support staff) with the new blended learning model for geospatial and information fluency? Focus groups (n = 7) plus one interview (total n = 22) were conducted with key stakeholders (e.g., staff, faculty, administrators) to better understand facilitators, barriers, and/or issues related to module development, in addition to perceptions about how the modules are utilized by teaching assistants (TAs), instructional assistants (IAs), and instructors. Participants were identified according to their status as either discipline-specific instructional staff (i.e., instructor, TA, IA) or staff who supported the development of modules (i.e., library instructional staff, library management, administrators). From an ontological standpoint that privileges an individual perspective on the nature of reality, while epistemologically seeking to understand the relationship between the "knower" and what can be known, we adopted a theory of constructivism to support this inquiry. Transcripts were imported into a qualitative analysis software package (NVivo 8.0) for organization, coding and analysis. Instructors found value in the online modules, particularly in a blended learning setting. Instructors felt that having the material in advance, in-class time could be better focused on interaction, assignments, and assessments and resulted in reduced anxiety in busy lab environments. Several key themes emerged, including: (a) instructor expectations (time constraints, sustainability, and collaborative nature of development process) and assessment (student grades and performance); (b) implementation benefits (course content consistency, more lab time devoted to instructor support, provision of additional course resources, and opportunities for student reflection; (c) implementation challenges (inadequate support for information literacy, perceptions of an increase in student workload, and definitional issues surrounding blended learning); (d) course-tailored modules (dichotomy of needs--course tailored vs. generic modules, value in a quiz component, and changing context of lab environment); and (e) key areas for improvement. Focus group respondents illustrated the importance of engaging students in the process of blended learning model development. Future iterations of blended learning modules should explicitly incorporate student feedback through focus groups during their development.

IntroductionAdolescent girls and young women (AGYW) face barriers in accessing clinic-based HIV pre-exposure prophylaxis (PrEP) services and community-based models are a proposed alternative. Evidence from such models, however, is limited. We evaluated PrEP service coverage, uptake, and early persistence among AGYW receiving services through community and hybrid models in Namibia.MethodsWe analyzed routine data for AGYW aged 15-24 who initiated PrEP within HIV prevention programming. PrEP was delivered via three models: community-concierge (fully community-based services with individually-tailored refill locations), community-fixed (community-based initiation and refills delivered by community providers on a set schedule at fixed sites), and hybrid community-clinic (community-based initiation and referral to clinics for refills delivered by clinic providers). We examined proportions of AGYW engaged in services along a programmatic PrEP cascade, overall and by model, and assessed factors associated with PrEP uptake and early persistence (refill within 15-44 days after initiation) using multivariable generalized estimating equations.ResultsOver 10-months, 7593 AGYW participated in HIV prevention programming. Of these, 7516 (99.0%) received PrEP education, 6105 (81.2%) received HIV testing services, 6035 (98.9%) tested HIV-negative, and 2225 (36.9%) initiated PrEP. Of the 2047 AGYW expected for PrEP refill during the study period, 254 (12.4%) persisted with PrEP one-month after initiation. Structural and behavioral HIV risk factors including early school dropout, food insecurity, inconsistent condom use, and transactional sex were associated with PrEP uptake. AGYW who delayed starting PrEP were 2.89 times more likely to persist (95% confidence interval (CI): 1.52-5.46) and those receiving services via the community-concierge model were 8.7 times (95% CI: 5.44-13.9) more likely to persist (compared to the hybrid model).ConclusionCommunity-based models of PrEP service delivery to AGYW can achieve high PrEP education and HIV testing coverage and moderate PrEP uptake. AGYW-centered approaches to delivering PrEP refills can promote higher persistence.

BackgroundIn vitro fertilisation (IVF) is a common mode of conception. Understanding the long-term implications for these children is important. The aim of this study was to determine the causal effect of IVF conception on primary school-age childhood developmental and educational outcomes, compared with outcomes following spontaneous conception.Methods and findingsCausal inference methods were used to analyse observational data in a way that emulates a target randomised clinical trial. The study cohort comprised statewide linked maternal and childhood administrative data. Participants included singleton infants conceived spontaneously or via IVF, born in Victoria, Australia between 2005 and 2014 and who had school-age developmental and educational outcomes assessed. The exposure examined was conception via IVF, with spontaneous conception the control condition. Two outcome measures were assessed. The first, childhood developmental vulnerability at school entry (age 4 to 6), was assessed using the Australian Early Developmental Census (AEDC) (n = 173,200) and defined as scoring ConclusionsIn this analysis, under the given causal assumptions, the school-age developmental and educational outcomes for children conceived by IVF are equivalent to those of spontaneously conceived children. These findings provide important reassurance for current and prospective parents and for clinicians.

An imbalance in the circulatory and organ-specific renin-angiotensin system (RAS) pathways is associated with age-related dysfunction and disease including cardiovascular burden and more recently Alzheimer’s disease (AD). It is currently unclear whether an age-associated imbalance in components of the RAS within the brain precedes the onset of AD or whether a RAS imbalance is associated with the onset of disease pathology and cognitive decline.Angiotensin-converting enzyme-1 (ACE-1) and -2 (ACE-2) protein (ELISA) and enzyme activity (FRET assay), markers of the classical and counter-regulatory RAS axis respectively, and Ang-II and Ang-(1–7) peptide levels (ELISA), were measured in the left cortex across four transgenic AD mouse models of amyloid pathology (5xFAD – 2, 6, and 12 months of age; Apd9 – 3-4, 12, and 18 months of age; Tg2576 – 3-4 and 24 months of age; and PDAPP – 3-4, 7, 11, 15, and 18 months of age) and littermate wild-type (WT) controls.ACE-1 level, and enzyme activity, was unaltered in relation to age in WT mice and across all four models. In contrast, ACE-2 level and enzyme activity, was reduced and Ang-II increased with ageing in both WT animals and disease models. The changes in ACE-2 and Ang-II in AD models mirrored WT mice, except for the 5xFAD model, when the reduction in ACE-2 (and elevated Ang-II) was observed at a younger age.These data indicate an age-related dysregulation of brain RAS is likely to be driven by a reduction in ACE-2. The reduction in ACE-2 occurs at a young age, coinciding with early pathological changes and the initial deposition of Aβ, and preceding neuronal loss and cognitive decline, in the transgenic AD models. However, the age-related loss was mirrored in WT mice suggesting that the change was independent of pathological Aβ deposition.

IntroductionDespite the potential for community-based approaches to increase access to pre-exposure prophylaxis (PrEP) for adolescent girls and young women (AGYW), there is limited evidence of whether and how they improve PrEP persistence. We compared PrEP persistence among AGYW receiving services through community and hybrid models in Namibia to facility-based services. We subsequently identify potential mechanisms to explain how and why community and hybrid models achieved (or not) improved persistence to inform further service delivery innovation.MethodsData were collected from PrEP service delivery to AGYW over two-years in Namibia's Khomas Region. We used Kaplan-Meier analysis to estimate survival curves for PrEP persistence beyond three-months after initiation and report the cumulative probability of persistence at one- and three-months. Persistence was defined as any PrEP use within three months after initiation followed by a PrEP refill or previously prescribed supply of at least 30 days at the three-month visit. Interviews were conducted with 28 AGYW and 19 providers and analyzed using a deductive-inductive thematic approach.ResultsFrom October 2017 through September 2019, 372 (18.7%) AGYW received services through a facility model, 302 (15.1%) through a community model, and 1,320 (66.2%) through a hybrid model. PrEP persistence at one- and three-months was 41.2% and 34.9% in the community model and 6.2% and 4.8% in the hybrid model compared to 36.8% and 26.7% in the facility model. Within the community and hybrid models, we identified three potential mechanisms related to PrEP persistence. Individualized service delivery offered convenience and simplicity which enabled AGYW to overcome barriers to obtaining refills but did not work as well for highly mobile AGYW. Consistent interactions and shared experiences fostered social connectedness with providers and with peers, building social networks and support systems for PrEP use. PrEP and HIV-related stigma, however, was widely experienced outside of these networks. Community-to-facility referral for PrEP refill triggered apprehension towards unfamiliar PrEP services and providers in AGYW, which discouraged persistence.ConclusionService delivery approaches that offer convenience and simplicity and foster social connectedness may reduce access barriers and increase social support enabling AGYW to self-manage their PrEP use and achieve improved PrEP persistence.

BackgroundAnaphylaxis is a well-known feature of mastocytosis, particularly in relation to hymenoptera venom stings. It is therefore hypothesized that mastocytosis patients may also be predisposed to severe hypersensitivity reactions to certain medications including non-steroidal anti-inflammatory drugs (NSAIDs). For this reason, these patients are usually discouraged from using these drugs. The current study aimed to determine the prevalence and evaluate the severity of NSAID-related hypersensitivity reactions among patients with mastocytosis.MethodsA retrospective study was conducted among a total of 388 (≥18 years old) consecutive patients from two independent European mastocytosis centers, in Sweden and Italy. Patients underwent a thorough allergy work-up where self-reported NSAID-hypersensitivity reactions were re-evaluated by an allergist in the first cohort (202 patients) and results were validated in the second cohort (186 patients).ResultsOverall frequency of NSAID-hypersensitivity was 11.3% in the total study cohort. Most patients reacted with cutaneous symptoms (89%), whereas severe hypersensitivity reactions were infrequent with only 11 patients (2.8%) experiencing anaphylaxis. All NSAID-related hypersensitivity reactions had occurred before mastocytosis was diagnosed. There was no difference between the groups regarding gender, baseline tryptase levels or presence of atopy, asthma/rhinitis.ConclusionOur study indicates an approximate 4-fold increased prevalence of NSAID hypersensitivity among mastocytosis patients compared to the general population. However, most NSAID reactions were limited to the skin as the prevalence of overall anaphylaxis was infrequent. Our results support that mastocytosis patients with a known tolerance to NSAIDs can continue using these medications without special precautions, whereas those with a prior reaction to NSAIDs should undergo thorough allergy work-up, including drug challenges.

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.