A brainstem integrator for self-location memory and positional homeostasis in zebrafish.

To track and control self-location, animals integrate their movements through space. Representations of self-location are observed in the mammalian hippocampal formation, but it is unknown if positional representations exist in more ancient brain regions, how they arise from integrated self-motion, and by what pathways they control locomotion. Here, in a head-fixed, fictive-swimming, virtual-reality preparation, we exposed larval zebrafish to a variety of involuntary displacements. They tracked these displacements and, many seconds later, moved toward their earlier location through corrective swimming ("positional homeostasis"). Whole-brain functional imaging revealed a network in the medulla that stores a memory of location and induces an error signal in the inferior olive to drive future corrective swimming. Optogenetically manipulating medullary integrator cells evoked displacement-memory behavior. Ablating them, or downstream olivary neurons, abolished displacement corrections. These results reveal a multiregional hindbrain circuit in vertebrates that integrates self-motion and stores self-location to control locomotor behavior.

From Whole-Brain Data to Functional Circuit Models: The Zebrafish Optomotor Response.

Detailed descriptions of brain-scale sensorimotor circuits underlying vertebrate behavior remain elusive. Recent advances in zebrafish neuroscience offer new opportunities to dissect such circuits via whole-brain imaging, behavioral analysis, functional perturbations, and network modeling. Here, we harness these tools to generate a brain-scale circuit model of the optomotor response, an orienting behavior evoked by visual motion. We show that such motion is processed by diverse neural response types distributed across multiple brain regions. To transform sensory input into action, these regions sequentially integrate eye- and direction-specific sensory streams, refine representations via interhemispheric inhibition, and demix locomotor instructions to independently drive turning and forward swimming. While experiments revealed many neural response types throughout the brain, modeling identified the dimensions of functional connectivity most critical for the behavior. We thus reveal how distributed neurons collaborate to generate behavior and illustrate a paradigm for distilling functional circuit models from whole-brain data.

Reward expectations direct learning and drive operant matching in Drosophila.

Foraging animals must use decision-making strategies that dynamically adapt to the changing availability of rewards in the environment. A wide diversity of animals do this by distributing their choices in proportion to the rewards received from each option, Herrnstein's operant matching law. Theoretical work suggests an elegant mechanistic explanation for this ubiquitous behavior, as operant matching follows automatically from simple synaptic plasticity rules acting within behaviorally relevant neural circuits. However, no past work has mapped operant matching onto plasticity mechanisms in the brain, leaving the biological relevance of the theory unclear. Here, we discovered operant matching in Drosophila and showed that it requires synaptic plasticity that acts in the mushroom body and incorporates the expectation of reward. We began by developing a dynamic foraging paradigm to measure choices from individual flies as they learn to associate odor cues with probabilistic rewards. We then built a model of the fly mushroom body to explain each fly's sequential choice behavior using a family of biologically realistic synaptic plasticity rules. As predicted by past theoretical work, we found that synaptic plasticity rules could explain fly matching behavior by incorporating stimulus expectations, reward expectations, or both. However, by optogenetically bypassing the representation of reward expectation, we abolished matching behavior and showed that the plasticity rule must specifically incorporate reward expectations. Altogether, these results reveal the first synapse-level mechanisms of operant matching and provide compelling evidence for the role of reward expectation signals in the fly brain.

Closed-loop parameter optimization for patient-specific phrenic nerve stimulation.

BACKGROUND: Ventilator-induced diaphragm dysfunction occurs rapidly following the onset of mechanical ventilation and has significant clinical consequences. Phrenic nerve stimulation has shown promise in maintaining diaphragm function by inducing diaphragm contractions. Non-invasive stimulation is an attractive option as it minimizes the procedural risks associated with invasive approaches. However, this method is limited by sensitivity to electrode position and inter-individual variability in stimulation thresholds. This makes clinical application challenging due to potentially time-consuming calibration processes to achieve reliable stimulation. METHODS: We applied non-invasive electrical stimulation to the phrenic nerve in the neck in healthy volunteers. A closed-loop system recorded the respiratory flow produced by stimulation and automatically adjusted the electrode position and stimulation amplitude based on the respiratory response. By iterating over electrodes, the optimal electrode was selected. A binary search method over stimulation amplitudes was then employed to determine an individualized stimulation threshold. Pulse trains above this threshold were delivered to produce diaphragm contraction. RESULTS: Nine healthy volunteers were recruited. Mean threshold stimulation amplitude was 36.17 ± 14.34 mA (range 19.38-59.06 mA). The threshold amplitude for reliable nerve capture was moderately correlated with BMI (Pearson's r = 0.66, p = 0.049). Repeating threshold measurements within subjects demonstrated low intra-subject variability of 2.15 ± 1.61 mA between maximum and minimum thresholds on repeated trials. Bilateral stimulation with individually optimized parameters generated reliable diaphragm contraction, resulting in significant inhaled volumes following stimulation. CONCLUSION: We demonstrate the feasibility of a system for automatic optimization of electrode position and stimulation parameters using a closed-loop system. This opens the possibility of easily deployable individualized stimulation in the intensive care setting to reduce ventilator-induced diaphragm dysfunction.

Evaluation of 3D C-Arm Fluoroscopy versus Diagnostic CT for Deep Brain Stimulation Stereotactic Registration and Post-Operative Lead Localization.

INTRODUCTION: DBS efficacy depends on accuracy. CT-MRI fusion is established for both stereotactic registration and electrode placement verification. The desire to streamline DBS workflows, reduce operative time, and minimize patient transfers has increased interest in portable imaging modalities such as the Medtronic O-arm® and mobile CT. However, these remain expensive and bulky. 3D C-arm fluoroscopy (3DXT) units are a smaller and less costly alternative, albeit incompatible with traditional frame-based localization and without useful soft tissue resolution. We aimed to compare fusion of 3DXT and CT with pre-operative MRI to evaluate if 3DXT-MRI fusion alone is sufficient for accurate registration and reliable targeting verification. We further assess DBS targeting accuracy using a 3DXT workflow and compare radiation dosimetry between modalities. METHODS: Patients underwent robot-assisted DBS implantation using a workflow incorporating 3DXT which we describe. Two intra-operative 3DXT spins were performed for registration and accuracy verification followed by conventional CT post-operatively. Post-operative 3DXT and CT images were independently fused to the same pre-operative MRI sequence and co-ordinates generated for comparison. Registration accuracy was compared to 15 consecutive controls who underwent CT-based registration. Radial targeting accuracy was calculated and radiation dosimetry recorded. RESULTS: Data were obtained from 29 leads in 15 consecutive patients. 3DXT registration accuracy was significantly superior to CT with mean error 0.22 ± 0.03 mm (p < 0.0001). Mean Euclidean electrode tip position variation for CT to MRI versus 3DXT to MRI fusion was 0.62 ± 0.40 mm (range 0.0 mm-1.7 mm). In comparison, direct CT to 3DXT fusion showed electrode tip Euclidean variance of 0.23 ± 0.09 mm. Mean radial targeting accuracy assessed on 3DXT was 0.97 ± 0.54 mm versus 1.15 ± 0.55 mm on CT with differences insignificant (p = 0.30). Mean patient radiation doses were around 80% lower with 3DXT versus CT (p < 0.0001). DISCUSSION: Mobile 3D C-arm fluoroscopy can be safely incorporated into DBS workflows for both registration and lead verification. For registration, the limited field of view requires the use of frameless transient fiducials and is highly accurate. For lead position verification based on MRI co-registration, we estimate there is around a 0.4 mm discrepancy between lead position seen on 3DXT versus CT when corrected for brain shift. This is similar to that described in O-arm® or mobile CT series. For units where logistical or financial considerations preclude the acquisition of a cone beam CT or mobile CT scanner, our data support portable 3D C-arm fluoroscopy as an acceptable alternative with significantly lower radiation exposure.

A mixed-methods SWOT analysis of a medical student Balint group programme.

BACKGROUND: Balint groups use case-based discussions to explore, reflect on, and enhance the clinician-patient relationship. They facilitate the development of empathy and reflective practice and reduce burnout. This study aimed to explore how the benefits of a traditional Balint group format can be accessed and optimised for medical students during a one-year pilot programme. METHODS: Eight medical student Balint groups ran for six weeks during 2022-2023, with 90 students participating. Themes were identified from student feedback using qualitative content analysis. Group leaders kept reflective session notes and used these alongside student feedback to undertake a strengths, weaknesses, opportunities, and threats analysis. RESULTS: Strengths of the programme were emotional containment, learning to reflect, and community identity. Weaknesses were themed as strange situations, dragging along, and facilitator as an object. Opportunities were identified in expanding the scope and sharpening focus. Psychological defences and the engagement dilemma threatened the future success of the Balint group programme. DISCUSSION: Medical student Balint groups provide a unique space to combine learning and emotional support with personal, professional and community development. However, the traditional Balint group format may need adapting to be widely accessible to undergraduate learners. Sustainably integrating Balint groups into the medical school curriculum requires ongoing engagement work at both an individual and organisational level.

Seeing Is Believing: Photon Counting Computed Tomography Clearly Images Directional Deep Brain Stimulation Lead Segments and Markers After Implantation.

BACKGROUND AND OBJECTIVES: Directional deep brain stimulation (DBS) electrodes are increasingly used, but conventional computed tomography (CT) is unable to directly image segmented contacts owing to physics-based resolution constraints. Postoperative electrode segment orientation assessment is necessary because of the possibility of significant deviation during or immediately after insertion. Photon-counting detector (PCD) CT is a relatively novel technology that enables high resolution imaging while addressing several limitations intrinsic to CT. We show how PCD CT can enable clear in vivo imaging of DBS electrodes, including segmented contacts and markers for all major lead manufacturers. MATERIALS AND METHODS: We describe postoperative imaging and reconstruction protocols we have developed to enable optimal lead visualization. PCD CT images were obtained of directional leads from the three major manufacturers and fused with preoperative 3T magnetic resonance imaging (MRI). Radiation dosimetry also was evaluated and compared with conventional imaging controls. Orientation estimates from directly imaged leads were compared with validated software-based reconstructions (derived from standard CT imaging artifact analysis) to quantify congruence in alignment and directional orientation. RESULTS: High-fidelity images were obtained for 15 patients, clearly indicating the segmented contacts and directional markers both on CT alone and when fused to MRI. Our routine imaging protocol is described. Ionizing radiation doses were significantly lower than with conventional CT. For most leads, the directly imaged lead orientations and depths corresponded closely to those predicted by CT artifact-based reconstructions. However, unlike direct imaging, the software reconstructions were susceptible to 180° error in orientation assessment. CONCLUSIONS: High-resolution photon-counting CT can very clearly image segmented DBS electrode contacts and directional markers and unambiguously determine lead orientation, with lower radiation than in conventional imaging. This obviates the need for further imaging and may facilitate anatomically tailored directional programming.

The Neurostimulation Appropriateness Consensus Committee (NACC)®: Recommendations for Spinal Cord Stimulation Long-term Outcome Optimization and Salvage Therapy.

INTRODUCTION: The International Neuromodulation Society (INS) has recognized a need to establish best practices for optimizing implantable devices and salvage when ideal outcomes are not realized. This group has established the Neurostimulation Appropriateness Consensus Committee (NACC)® to offer guidance on matters needed for both our members and the broader community of those affected by neuromodulation devices. MATERIALS AND METHODS: The executive committee of the INS nominated faculty for this NACC® publication on the basis of expertise, publications, and career work on the issue. In addition, the faculty was chosen in consideration of diversity and inclusion of different career paths and demographic categories. Once chosen, the faculty was asked to grade current evidence and along with expert opinion create consensus recommendations to address the lapses in information on this topic. RESULTS: The NACC® group established informative and authoritative recommendations on the salvage and optimization of care for those with indwelling devices. The recommendations are based on evidence and expert opinion and will be expected to evolve as new data are generated for each topic. CONCLUSIONS: NACC® guidance should be considered for any patient with less-than-optimal outcomes with a stimulation device implanted for treating chronic pain. Consideration should be given to these consensus points to salvage a potentially failed device before explant.

Surface viscosities of lipid bilayers determined from equilibrium molecular dynamics simulations.

Lipid membrane viscosity is critical to biological function. Bacterial cells grown in different environments alter their lipid composition in order to maintain a specific viscosity, and membrane viscosity has been linked to the rate of cellular respiration. To understand the factors that determine the viscosity of a membrane, we ran equilibrium all-atom simulations of single component lipid bilayers and calculated their viscosities. The viscosity was calculated via a Green-Kubo relation, with the stress-tensor autocorrelation function modeled by a stretched exponential function. By simulating a series of lipids at different temperatures, we establish the dependence of viscosity on several aspects of lipid chemistry, including hydrocarbon chain length, unsaturation, and backbone structure. Sphingomyelin is found to have a remarkably high viscosity, roughly 20 times that of DPPC. Furthermore, we find that inclusion of the entire range of the dispersion interaction increases viscosity by up to 140%. The simulated viscosities are similar to experimental values obtained from the rotational dynamics of small chromophores and from the diffusion of integral membrane proteins but significantly lower than recent measurements based on the deformation of giant vesicles.

Mortality rates and proximal causes of death in patients with Lewy body dementia versus Alzheimer's disease: A longitudinal study using secondary care mental health records.

BACKGROUND: Previous studies have shown reduced survival in Lewy body dementia (LBD) compared to Alzheimer's disease (AD), but the reasons for this are not known. We identified cause of death categories accounting for the reduced survival in LBD. METHODS: We linked cohorts of patients with dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD) and AD, with proximal cause of death data. We examined mortality by dementia group and hazard ratios for each death category by dementia group in males and females separately. In a specific focus on the dementia group with the highest mortality rate versus reference, we examined cumulative incidence to identify the main causes of death accounting for the excess deaths. RESULTS: Hazard ratios for death were higher in PDD and DLB compared to AD, for both males and females. PDD males had the highest hazard ratio for death across the dementia comparison groups (HR 2.7, 95% CI 2.2-3.3). Compared with AD, hazard ratios for "nervous system" causes of death were significantly elevated in all LBD groups. Additional significant cause-of-death categories included aspiration pneumonia, genitourinary causes, other respiratory causes, circulatory and a "symptoms and signs" category in PDD males; other respiratory causes in DLB males; mental disorders in PDD females; and aspiration pneumonia, genitourinary and other respiratory causes in DLB females. CONCLUSION: Further research and cohort development is required to investigate differences by age group, to extend cohort follow-up to the whole population and to investigate the risk-balance of interventions which may differ by dementia group.

[Recommendations for the development of resilient health systems in the AmericasRecomendações para o desenvolvimento de sistemas de saúde resilientes nas Américas]. / Recomendaciones para el desarrollo de sistemas de salud resilientes en las Américas.

This article offers opinion and analysis outlining strategic lines of action to build resilient health systems while promoting recovery in the post-COVID-19 pandemic period, with a view to maintaining and protecting public health gains. It contextualizes the challenges and opportunities in the Region of the Americas and offers recommendations for implementation of the strategic lines.It is urgent to promote the development of resilient health systems through the implementation of four lines of action defined in the strategy adopted by the Member States of the Pan American Health Organization in September 2021. The transformation of health systems must be based on the adoption of an integrated model of primary health care, a priority focus on the essential public health functions, strengthening of integrated health service networks, and increased public funding, especially for the first level of care. Implementation of these lines of action is focused not only on consolidating immediate crisis response; it is also framed within efforts toward the recovery and sustainable development of health systems, reducing their structural vulnerabilities to better prepare the response to future crises.

Este artigo de opinião e análise descreve linhas de ação estratégicas para desenvolver sistemas de saúde resilientes ao mesmo tempo em que se promove a recuperação pós-pandemia de COVID-19 a fim de manter e proteger os ganhos em saúde pública. Além disso, apresenta uma contextualização dos desafios e oportunidades na região das Américas e oferece recomendações para sua implementação. Há uma necessidade urgente de promover o desenvolvimento de sistemas de saúde resilientes por meio da implementação das quatro linhas de ação definidas na estratégia adotada pelos Estados Membros da Organização Pan-Americana da Saúde em setembro de 2021. A transformação dos sistemas de saúde deve se basear na adoção de um modelo integral de atenção primária à saúde; na priorização das funções essenciais de saúde pública; no fortalecimento de redes integrais de serviços de saúde; e no aumento do financiamento público, especialmente para o primeiro nível de atenção. A implementação dessas linhas de ação busca não apenas consolidar a resposta imediata à crise, mas também enquadrá-la nos esforços de recuperação e desenvolvimento sustentável dos sistemas de saúde, reduzindo suas vulnerabilidades estruturais para que fiquem mais bem preparados para responder a futuras crises.

Using mixed methods to understand and tackle barriers to accessing health services.

This report describes the experience and lessons learnt from designing and implementing a combined quantitative and qualitative method to assess barriers to accessing health services. This approach was developed to study barriers to access in five dimensions: availability; geographical, financial, and organizational accessibility; acceptability; contact; and effective coverage. The study design was used in six countries in the World Health Organization Region of the Americas. The findings highlight the importance of having a well defined analysis framework and the benefits of adopting a mixed-methods approach. Using existing data and contextualizing findings according to specific population groups and geographical areas were essential for relevance and utilization of the study outcomes. The findings demonstrate the feasibility of using mixed methods to understand the complexity of access problems faced by different subpopulations. By involving decision-makers from the beginning and allowing flexibility for sustained discussions, the analysis and findings had an impact. The engagement of health authorities and key stakeholders facilitated the use of the findings for collaborative identification of policy options to eliminate access barriers. Lessons learnt from the study emphasized the need for active participation of decision-makers, flexibility in the process, and sustained opportunities for discussion to ensure impact. Giving consideration to local priorities and adapting the methods accordingly were important for the relevance and use of the findings. Future efforts could consider incorporating mixed methods into national and local monitoring and evaluation systems.

En este informe se describen la experiencia y las enseñanzas extraídas a partir del diseño y la aplicación de un método que combina elementos cuantitativos y cualitativos para evaluar los obstáculos que dificultan el acceso a los servicios de salud. Este enfoque se ideó para poder analizar estos obstáculos mediante cinco dimensiones: disponibilidad; accesibilidad geográfica, económica y organizativa; aceptabilidad; contacto; y cobertura efectiva. El diseño del estudio se utilizó en seis países de la Región de las Américas de la Organización Mundial de la Salud. Los resultados pusieron de relieve la importancia de contar con un marco de análisis bien definido, así como las ventajas de adoptar un enfoque basado en métodos mixtos. El uso de los datos existentes y la contextualización de los resultados en función de grupos poblacionales y áreas geográficas específicos fueron aspectos esenciales para el interés y la aplicación de los resultados del estudio. Los resultados demuestran la viabilidad del uso de métodos mixtos para comprender la complejidad de los problemas de acceso que afrontan los diferentes subgrupos poblacionales. La involucración desde un primer momento de las personas responsables de la toma de decisiones y la flexibilidad para llevar a cabo deliberaciones prolongadas propiciaron una mayor repercusión del análisis y sus conclusiones. La participación de las autoridades de salud y de las principales partes interesadas favoreció la aplicación de los resultados para determinar, en un marco de colaboración, las opciones políticas necesarias para eliminar los obstáculos que dificultan el acceso. Las enseñanzas extraídas de este estudio subrayan la necesidad de una participación activa de las autoridades responsables de la toma de decisiones, de que el proceso sea flexible y de la existencia de oportunidades permanentes de deliberación para asegurar su eficacia. El hecho de tener en cuenta las prioridades locales y adaptar los métodos en consecuencia fue un elemento importante para el interés y la aplicación de los resultados. Las iniciativas futuras podrían considerar la incorporación de métodos mixtos a los sistemas nacionales y locales de seguimiento y evaluación.

Este relatório descreve a experiência e as lições aprendidas com o delineamento e implementação de um método combinado (quantitativo e qualitativo) para avaliar barreiras de acesso aos serviços de saúde. Essa abordagem foi desenvolvida para estudar barreiras de acesso em cinco dimensões: disponibilidade; acessibilidade geográfica, financeira e organizacional; aceitabilidade; contato; e cobertura efetiva. O desenho do estudo foi usado em seis países da Região das Américas da Organização Mundial da Saúde. Os achados destacam a importância de ter uma estrutura de análise bem definida e os benefícios de adotar uma abordagem de métodos mistos. O uso de dados existentes e a contextualização dos achados de acordo com grupos populacionais e áreas geográficas específicas foram essenciais para a relevância e a utilização dos resultados do estudo. Os achados demonstram a viabilidade de usar métodos mistos para entender a complexidade dos problemas de acesso enfrentados por diferentes subpopulações. O envolvimento de tomadores de decisão desde o início e a flexibilidade para discussões contínuas permitiram que a análise e os achados tivessem impacto. O envolvimento das autoridades sanitárias e das principais partes interessadas facilitou a utilização dos achados na identificação colaborativa de opções de políticas para eliminar as barreiras de acesso. As lições aprendidas com o estudo enfatizaram a necessidade de participação ativa dos tomadores de decisão, flexibilidade no processo e oportunidades contínuas de discussão para assegurar seu impacto. Foi importante levar em consideração as prioridades locais e adaptar os métodos de acordo com essas prioridades para garantir a relevância e o uso dos achados. Futuros esforços podem considerar a incorporação de métodos mistos em sistemas nacionais e locais de monitoramento e avaliação.

[The importance of a gender focus in building resilient, equitable, and universal health systemsA importância da abordagem de gênero no desenvolvimento de sistemas de saúde resilientes, equitativos e universais]. / La importancia del enfoque de género en la construcción de sistemas de salud resilientes, equitativos y universales.

The coronavirus disease 2019 (COVID-19) pandemic demonstrated the need to strengthen the focus on gender from an integrative and multisectoral perspective to address health care problems. This article seeks to highlight the importance of incorporating and strengthening the gender focus in policies for building resilient, equitable, and universal health care systems. With this objective in mind, the role of women in the health sector is addressed from two directions. The first examines women's conditions of access to health systems in the Region of the Americas and highlights the need to overcome the obstacles that prevent the full realization of their right to health care. The second discusses the preponderant role of women in the health labor market, and the need to expand their leadership in decision-making in the sector. Finally, an appeal is made for progress in the implementation of recommendations to strengthen the focus on gender and the role of women in health policies and systems.

A pandemia da doença do coronavírus de 2019 (COVID-19) demonstrou a necessidade de fortalecer a abordagem de gênero a partir de uma perspectiva integradora e multissetorial ao tratar das questões de saúde. Este artigo procura ressaltar a importância de incorporar e fortalecer a abordagem de gênero nas políticas para o desenvolvimento de sistemas de saúde resilientes, equitativos e universais. Com esse objetivo, este trabalho aborda o papel das mulheres no setor da saúde a partir de duas perspectivas. A primeira está ligada às condições de acesso das mulheres aos sistemas de saúde na Região das Américas, destacando a necessidade de superar os obstáculos que impedem o pleno exercício de seu direito à saúde. A segunda destaca o papel proeminente das mulheres no mercado de trabalho do setor da saúde e a necessidade de aumentar o seu papel de liderança na tomada de decisões no setor. Por fim, é feito um apelo para avançar com a implementação de recomendações destinadas a fortalecer a abordagem de gênero e o papel das mulheres nas políticas e sistemas de saúde.

Deep Brain Stimulation and Levodopa Affect Gait Variability in Parkinson Disease Differently.

BACKGROUND: Both dopaminergic medication and subthalamic nucleus (STN) deep brain stimulation (DBS) can improve the amplitude and speed of gait in Parkinson disease (PD), but relatively little is known about their comparative effects on gait variability. Gait irregularity has been linked to the degeneration of cholinergic neurons in the pedunculopontine nucleus (PPN). OBJECTIVES: The STN and PPN have reciprocal connections, and we hypothesized that STN DBS might improve gait variability by modulating PPN function. Dopaminergic medication should not do this, and we therefore sought to compare the effects of medication and STN DBS on gait variability. MATERIALS AND METHODS: We studied 11 patients with STN DBS systems on and off with no alteration to their medication, and 15 patients with PD without DBS systems on and off medication. Participants walked for two minutes in each state, wearing six inertial measurement units. Variability has previously often been expressed in terms of SD or coefficient of variation over a testing session, but these measures conflate long-term variability (eg, gradual slowing, which is not necessarily pathological) with short-term variability (true irregularity). We used Poincaré analysis to separate the short- and long-term variability. RESULTS: DBS decreased short-term variability in lower limb gait parameters, whereas medication did not have this effect. In contrast, STN DBS had no effect on arm swing and trunk motion variability, whereas medication increased them, without obvious dyskinesia. CONCLUSIONS: Our results suggest that STN DBS acts through a nondopaminergic mechanism to reduce gait variability. We believe that the most likely explanation is the retrograde activation of cholinergic PPN projection neurons.

Mindfulness-Based Group Therapy for Chronic Pain Management in Older Adults.

OBJECTIVES: There were two quality improvement goals for this project: (1) to evaluate the outcomes of an 8-week geriatric-focused mindfulness-based group therapy program for chronic pain management called "Mindfulness-based Chronic Pain Care" offered at a senior community center affiliated with a geriatric primary care clinic, and (2) to obtain feedback from participants to make relevant modifications for future groups. METHODS: The program consisted of eight 150-minute weekly sessions. Thirteen community-dwelling older adults aged 60 and older participated in the program. The study utilized a non-randomized control-group pretest-posttest design. Participants completed pre- and post-program evaluations measuring pain and related psychosocial outcomes and were also asked to evaluate the importance of the group. Intervention and control groups were compared by t-test, chi-square likelihood ratio, Fischer's exact test, and multivariate analysis of variance with repeated measures. RESULTS: There were statistically significant improvements in three areas: 1) increased activity level, 2) increased "pain willingness," and 3) decreased generalized anxiety symptoms. Qualitative analysis highlighted how this intervention was important to participants. CONCLUSIONS: The results of this pilot program indicate promising outcomes for older adults suffering from chronic pain. CLINICAL IMPLICATIONS: The Mindfulness-based Chronic Pain Care program was a practical, feasible, and acceptable approach for pain management among program participants.

Identifying access barriers faced by rural and dispersed communities to better address their needs: implications and lessons learned for rural proofing for health in the Americas and beyond.

INTRODUCTION: Universal access to health services and universal health coverage are needed to achieve good health for all, yet rural communities face a variety of access barriers. As part of an effort to 'rural proof' health systems, it is therefore imperative to identify and act on the factors limiting access to health services by rural and indigenous communities. This article provides a comprehensive overview of the wide range of access barriers faced by rural and remote communities in two countries where barrier assessments were conducted. It also discusses the potential for barrier assessments to contribute evidence for rural proofing of national health policies, strategies, plans and programs. METHODS: The study applied a concurrent triangulation design to collect and analyze data obtained from narrative-style literature reviews, in-depth interviews with local health authorities, and secondary analyses of existing household data on Guyana and Peru. These two countries were selected because they have some of the largest rural and indigenous populations in Latin America and the Caribbean, and have national policies in place for providing free, essential health services for these communities. Both quantitative and qualitative data were collected separately, and results were interpreted together. The main objective was to corroborate and cross-validate findings looking for convergence between the separate data analyses. RESULTS: Seven dominant themes were identified across the two countries: use of traditional medicine and practice; decision making, gender, and family power dynamics; ethnicity and trust; knowledge and health literacy; geographic accessibility, health personnel and intercultural skills; and financial accessibility. The findings suggest that the interaction between these barriers may be as important as the singular role played by each factor, thereby highlighting the complex and multifactorial nature of accessing services in rural settings. Issues with limited availability of human resources for health were compounded by inadequate supplies and infrastructure. Financial barriers were often linked to the indirect costs of transport and geographic location, and further exacerbated by reduced socioeconomic status of rural communities, a majority of which are indigenous and have a strong preference for traditional medicines. Importantly, rural and indigenous communities experience considerable non-financial barriers related to issues of acceptability, which requires adaptation of health personnel and health service delivery models to the context-specific needs and realities of each rural community. CONCLUSION: This study presented an approach for data collection and analysis that is both feasible and effective for evaluating access barriers in rural and remote communities. While this study explored access barriers through general health services in two rural settings, the issues identified reflect the structural deficiencies of many health systems. These challenges and singularities require adaptive organizational models for the provision of health services that respond to the specific characteristics of rural and indigenous communities. This study indicates the potential relevance of conducting assessments of barriers to health services as part of a wider approach to rural proofing and supports the notion that a mixed-methods approach, linking secondary analysis of existing relevant national survey data with focused key-informant interview data, may be an effective and efficient way to transform data into the knowledge policymakers need to rural proof health policies.

Exact learning dynamics of deep linear networks with prior knowledge.

Learning in deep neural networks is known to depend critically on the knowledge embedded in the initial network weights. However, few theoretical results have precisely linked prior knowledge to learning dynamics. Here we derive exact solutions to the dynamics of learning with rich prior knowledge in deep linear networks by generalising Fukumizu's matrix Riccati solution (Fukumizu 1998 Gen 1 1E-03). We obtain explicit expressions for the evolving network function, hidden representational similarity, and neural tangent kernel over training for a broad class of initialisations and tasks. The expressions reveal a class of task-independent initialisations that radically alter learning dynamics from slow non-linear dynamics to fast exponential trajectories while converging to a global optimum with identical representational similarity, dissociating learning trajectories from the structure of initial internal representations. We characterise how network weights dynamically align with task structure, rigorously justifying why previous solutions successfully described learning from small initial weights without incorporating their fine-scale structure. Finally, we discuss the implications of these findings for continual learning, reversal learning and learning of structured knowledge. Taken together, our results provide a mathematical toolkit for understanding the impact of prior knowledge on deep learning.

Association between antidementia medication use and mortality in people diagnosed with dementia with Lewy bodies in the UK: A retrospective cohort study.

BACKGROUND: Dementia with Lewy bodies (DLBs) is a common cause of dementia but has higher mortality than Alzheimer's disease (AD). The reasons for this are unclear, but antidementia drugs (including acetylcholinesterase inhibitors [AChEIs] and memantine) symptomatically benefit people with DLB and might improve outcomes. We investigated whether AChEIs and/or memantine were associated with reduced hospital admissions and mortality. METHODS AND FINDINGS: We performed a retrospective cohort study of those diagnosed with DLB between 1 January 2005 and 31 December 2019, using data from electronic clinical records of secondary care mental health services in Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), United Kingdom (catchment area population approximately 0.86 million), as well as linked records from national Hospital Episode Statistics (HES) data. Eligible patients were those who started AChEIs or memantine within 3 months of their diagnosis (cases) and those who never used AChEIs or memantine (controls). Outcomes included admission, length of stay, and mortality. Cox proportional hazard and linear regression models were used. Of 592 patients with DLB, 219 never took AChEIs or memantine, 100 took AChEIs only, and 273 took both AChEIs and memantine. The cohorts were followed up for an average of 896 days, 981 days, and 1,004 days, respectively. There were no significant differences in the cohorts' baseline characteristics, except for socioeconomic status that was lower in patients who never took AChEIs or memantine (χ2 = 23.34, P = 0.003). After controlling for confounding by sociodemographic factors (age, sex, marital status, ethnicity, socioeconomic status), antipsychotic use, antidepressant use, cognitive status, physical comorbidity, anticholinergic burden, and global health performance, compared with patients who never took AChEIs or memantine, patients taking AChEIs only or taking both had a significantly lower risk of death (adjusted hazard ratio (HR) = 0.67, 95% CI = 0.48 to 0.93, p = 0.02; adjusted HR = 0.64, 95% CI = 0.50 to 0.83, P = 0.001, respectively). Those taking AChEIs or both AChEIs and memantine had significantly shorter periods of unplanned hospital admission for physical disorders (adjusted coefficient -13.48, 95% CI = [-26.87, -0.09], P = 0.049; adjusted coefficient -14.21, 95% CI = [-24.58, -3.85], P = 0.007, respectively), but no difference in length of stay for planned admissions for physical disorders, or for admissions for mental health disorders. No significant additional associations of memantine on admission, length of stay, and mortality were found (all P > 0.05). The main limitation was that this was a naturalistic study and possible confounds cannot be fully controlled, and there may be selection bias resulting from nonrandom prescription behaviour in clinical practice. However, we mimicked the intention-to-treat design of clinical trials, and the majority of baseline characters were balanced between cohorts. In addition, our series of sensitivity analyses confirmed the consistency of our results. CONCLUSION: In this study, we observed that use of AChEIs with or without memantine in DLB was associated with shorter duration of hospital admissions and decreased risk of mortality. Although our study was naturalistic, it supports further the use of AChEIs in DLB.

Longitudinal Monitoring of Progressive Supranuclear Palsy using Body-Worn Movement Sensors.

BACKGROUND: We have previously shown that wearable technology and machine learning techniques can accurately discriminate between progressive supranuclear palsy (PSP), Parkinson's disease, and healthy controls. To date these techniques have not been applied in longitudinal studies of disease progression in PSP. OBJECTIVES: We aimed to establish whether data collected by a body-worn inertial measurement unit (IMU) network could predict clinical rating scale scores in PSP and whether it could be used to track disease progression. METHODS: We studied gait and postural stability in 17 participants with PSP over five visits at 3-month intervals. Participants performed a 2-minute walk and an assessment of postural stability by standing for 30 seconds with their eyes closed, while wearing an array of six IMUs. RESULTS: Thirty-two gait and posture features were identified, which progressed significantly with time. A simple linear regression model incorporating the three features with the clearest progression pattern was able to detect statistically significant progression 3 months in advance of the clinical scores. A more complex linear regression and a random forest approach did not improve on this. CONCLUSIONS: The reduced variability of the models, in comparison to clinical rating scales, allows a significant change in disease status from baseline to be observed at an earlier stage. The current study sheds light on the individual features that are important in tracking disease progression. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Contributions of the New Framework for Essential Public Health Functions to Addressing the COVID-19 Pandemic.

This article uses a health stewardship perspective to interpret the strengths of and challenges to national health authorities' capacities to respond to the COVID-19 pandemic through the renewed essential public health functions (EPHF) framework. Based on a literature review, this article argues that the institutional capacities required by countries to respond to the COVID-19 pandemic in the Americas included all 4 stages of the new EPHF policy cycle: assessment, policy development, allocation of resources, and access. While health authorities provided these key functions (e.g., data analysis, intersectoral policy dialogues, allocation of additional funds), the interventions implemented depended on each country's own institutional structures. Health authorities faced significant challenges including fragmentation and the lack of institutional and personnel capacities, thus compromising the delivery of an effective and equitable response. In addition, the response to the pandemic has been uneven because of weaknesses in central leadership and coordination capacity, the politicization of the response, and differences in the capacity to respond at subnational levels. Such challenges reflect structural weaknesses that existed before the onset of the pandemic, as well as the low prioritization of public health in agendas for health systems strengthening. A future agenda should prioritize improving structural elements while strengthening the stewardship capacities of health authorities and developing institutional structures that guarantee access to and universal coverage of health services. (Am J Public Health. 2022;112(S6):S615-S620. https://doi.org/10.2105/AJPH.2022.306750).