Distribution theories for genetic line of least resistance and evolvability measures.

Quantitative genetic theory on multivariate character evolution predicts that a population's response to directional selection is biased toward the major axis of the genetic covariance matrix G-the so-called genetic line of least resistance. Inferences on the genetic constraints in this sense have traditionally been made by measuring the angle of deviation of evolutionary trajectories from the major axis, or more recently by calculating the amount of genetic variance-the Hansen-Houle evolvability-available along the trajectories. However, there have not been clear practical guidelines on how these quantities can be interpreted, especially in a high-dimensional space. This study summarizes pertinent distribution theories for relevant quantities, pointing out that they can be written as ratios of quadratic forms in evolutionary trajectory vectors by taking G as a parameter. For example, a beta distribution with appropriate parameters can be used as a null distribution for squared cosine of the angle of deviation from a major axis or subspace. More general cases can be handled with the probability distribution of ratios of quadratic forms in normal variables. Apart from its use in hypothesis-testing, this latter approach could potentially be used as a heuristic tool for looking into various selection scenarios like directional and/or correlated selection as parameterized with mean and covariance of selection gradients.

Rapid Compensation for Noisy Voluntary Movements in Adults with Primary Tic Disorders.

BACKGROUND: It has been proposed that tics and premonitory urges in primary tic disorders (PTD), like Tourette syndrome, are a manifestation of sensorimotor noise. However, patients with tics show no obvious movement imprecision in everyday life. One reason could be that patients have strategies to compensate for noise that disrupts performance (ie, noise that is task-relevant). OBJECTIVES: Our goal was to unmask effects of elevated sensorimotor noise on the variability of voluntary movements in patients with PTD. METHODS: We tested 30 adult patients with PTD (23 male) and 30 matched controls in a reaching task designed to unmask latent noise. Subjects reached to targets whose shape allowed for variability either in movement direction or extent. This enabled us to decompose variability into task-relevant versus less task-relevant components, where the latter should be less affected by compensatory strategies than the former. In alternating blocks, the task-relevant target dimension switched, allowing us to explore the temporal dynamics with which participants adjusted movement variability to changes in task demands. RESULTS: Both groups accurately reached to targets, and adjusted movement precision based on target shape. However, when task-relevant dimensions of the target changed, patients initially produced movements that were more variable than controls, before regaining precision after several reaches. This effect persisted across repeated changes in the task-relevant dimension across the experiment, and therefore did not reflect an effect of novelty, or differences in learning. CONCLUSIONS: Our results suggest that patients with PTD generate noisier voluntary movements compared with controls, but rapidly compensate according to current task demands. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

SWAT model applications: From hydrological processes to ecosystem services.

Ecosystem services in bolstering human well-being and steering environmental management garnered increasing recognition. In this realm, the Soil and Water Assessment Tool (SWAT) rose as an instrumental tool in ecosystem services. The heterogeneous applications of SWAT across diverse studies underscore an imperative for bibliometric analysis to decipher these evolving trends. This study endeavors to execute a comprehensive analysis of SWAT's application for ecosystem services, delineating key thematic development and exploring its utilization in ecosystem services. We conducted a comprehensive literature review by searching the Web of Science database, retrieving a total of 534 articles. The CiteSpace facilitated our co-citation analysis, enabling the identification of seminal publications and burgeoning themes within SWAT. Our analysis delineated thematic development in SWAT pertaining to ecosystem services. Initially concentrated on hydrological processes, the focus progressively broadened to encompass comprehensive ecosystem services evaluations. We examined 81 peer-reviewed publications directly related to ecosystem services, and most of them addressed certain ecosystem services, such as water yield, soil retention, regulation of water flow, food, and carbon storage. SWAT holds a unique advantage in quantifying water-related processes. Future studies should focus more on ecosystem service flows based on SWAT, which contributes to elucidating the relationship between nature and humans, facilitating comprehensive ecosystem management.

Orthogonal multimodality integration and clustering in single-cell data.

Multimodal integration combines information from different sources or modalities to gain a more comprehensive understanding of a phenomenon. The challenges in multi-omics data analysis lie in the complexity, high dimensionality, and heterogeneity of the data, which demands sophisticated computational tools and visualization methods for proper interpretation and visualization of multi-omics data. In this paper, we propose a novel method, termed Orthogonal Multimodality Integration and Clustering (OMIC), for analyzing CITE-seq. Our approach enables researchers to integrate multiple sources of information while accounting for the dependence among them. We demonstrate the effectiveness of our approach using CITE-seq data sets for cell clustering. Our results show that our approach outperforms existing methods in terms of accuracy, computational efficiency, and interpretability. We conclude that our proposed OMIC method provides a powerful tool for multimodal data analysis that greatly improves the feasibility and reliability of integrated data.

The emergence and regression of political priority for refugee integration into the Jordanian health system: an analysis using the Kingdon's multiple streams model.

BACKGROUND: The prolonged presence of Syrian refugees in Jordan has highlighted the need for sustainable health service delivery models for refugees. In 2012, the Jordanian government adopted a policy that granted Syrian refugees access, free of charge, to the national health system. However since 2012, successive policy revisions have limited refugee access. This paper seeks to understand factors that initially put refugee integration into the health system on the policy agenda, as well as how these same factors later affected commitment to sustain the policy. METHODS: This paper draws on data from a document review of 197 peer-reviewed and grey literature publications, a media analysis of newspaper articles retrieved from four officially recognized newspapers in Jordan, and 33 semi-structured key informant interviews. We used Kingdon's Multiple Streams Model - a well-established tool for analyzing policy adoption - to understand how political priority developed for integration of refugees into the health system. RESULTS: We find that several factors helped bring attention to the issue, namely concerns over infectious disease transmission to host communities, high rates of chronic conditions among the refugee population and the increasingly urban and dispersed nature of refugees. At the outset of the conflict, the national mood was receptive to refugees. Politicians and government officials quickly recognized the crisis as an opportunity to secure material and technical support from the international humanitarian community. At the same time, global pressures for integrating refugees into national health systems helped move the integration agenda forward in Jordan and the region more broadly. Since 2012, there were several modifications to the policy that signal profound changes in national views around the continued presence of Syrian refugees in the country, as well as reduced external financial support which has undermined the sustainability of the policy. CONCLUSION: This case study underscores the dynamic nature of policymaking and the challenge of sustaining government commitment to the right to health among refugees. Our analysis has important implications for advocates seeking to advance and maintain momentum for the integration of refugees into national health systems.

How integration of refugees into national health systems became a global priority: a qualitative policy analysis.

BACKGROUND: Despite a long history of political discourse around refugee integration, it wasn't until 2016 that this issue emerged as a global political priority. Limited research has examined the evolution of policies of global actors around health service provision to refugees and how refugee integration into health systems came onto the global agenda. This study seeks to fill this gap. METHODS: Drawing on a document review of 20 peer-reviewed articles, 46 global policies and reports, and 18 semi-structured interviews with actors representing various bilateral, multilateral and non-governmental organizations involved with refugee health policy and funding, we analyze factors that have shaped the global policy priority of integration. We use the Shiffman and Smith Policy Framework on determinants of political priority to organize our findings. RESULTS: Several important factors generated global priority for refugee integration into national health systems. Employing the above-mentioned framework, actor power increased due to network expansion through collaborations between humanitarian and development actors. Ideas took hold through the framing of integration as a human rights and responsibility sharing. While political context was influenced through several global movements, it was ultimately the influx of Syrian refugees into Europe and the increasing securitization of the refugee crisis that led to key policies, and critically, global funding to support integration within refugee hosting nations. Finally, issue characteristics, namely the magnitude of the global refugee crisis, its protractedness and the increasing urbanicity of refugee inflows, led integration to emerge as a manageable solution. CONCLUSION: The past decade has seen a substantial reframing of refugee integration, along with increased financing sources and increased collaboration, explains this shift towards their integration into health systems. However, despite the emergence of integration as a global political priority, the extent to which efforts around integration have translated into action at the national level remains uncertain.

'We get to learn as we move': effects and feasibility of lesson-integrated physical activity in a Swedish primary school.

BACKGROUND: Physical activity (PA) promotes health in adults as well as children. At the same time, a large proportion of children do not meet the recommendations for PA, and more school-based efforts to increase PA are needed. This study investigates the effectiveness and feasibility of lesson-integrated PA in a Swedish primary school. METHODS: We evaluate a new method called 'Physical Activity and Lesson in Combination' (abbreviated FALK in Swedish) using a mixed methods approach; a quasi-experimental study followed by qualitative interviews. Two schools participated in the study, one constituting the intervention group (I-school, n = 83) and the other the control group (C-school, n = 81). In addition to regular physical education, the I-school had three 30-minute FALK lessons each week. A total of 164 students aged 7-9 years wore pedometers for a whole week, four times over two semesters, and the number of steps per day (SPD) and the proportion of students with < 10,000 SPD were compared. Statistical differences between the schools were tested with ANOVA, Chi2, t-tests, and ANCOVA. Interviews with students (n = 17), parents (n = 9) and teachers (n = 9) were conducted and analysed using qualitative content analysis. RESULTS: The results show that FALK led to the I-school getting more SPD and fewer students with < 10,000 SPD. Also, FALK was experienced as a positive, clear, and flexible method, simultaneously encouraging PA and learning. Challenges experienced concerned the teachers' work situation, time, finding suitable learning activities, outdoor school environment changes, and extreme weather conditions. CONCLUSIONS: This study indicates that FALK has the desired effects on PA and is a feasible method of integrating PA into theoretical teaching. We conclude that FALK is worth testing at more schools, given that implementation and sustainment of FALK considers both general enablers and barriers, as well as context-specific factors at the individual school.

Metabolic and inflammatory perturbation of diabetes associated gut dysbiosis in people living with and without HIV infection.

BACKGROUND: Gut dysbiosis has been linked with both HIV infection and diabetes, but its interplay with metabolic and inflammatory responses in diabetes, particularly in the context of HIV infection, remains unclear. METHODS: We first conducted a cross-sectional association analysis to characterize the gut microbial, circulating metabolite, and immune/inflammatory protein features associated with diabetes in up to 493 women (~ 146 with prevalent diabetes with 69.9% HIV +) of the Women's Interagency HIV Study. Prospective analyses were then conducted to determine associations of identified metabolites with incident diabetes over 12 years of follow-up in 694 participants (391 women from WIHS and 303 men from the Multicenter AIDS Cohort Study; 166 incident cases were recorded) with and without HIV infection. Mediation analyses were conducted to explore whether gut bacteria-diabetes associations are explained by altered metabolites and proteins. RESULTS: Seven gut bacterial genera were identified to be associated with diabetes (FDR-q < 0.1), with positive associations for Shigella, Escherichia, Megasphaera, and Lactobacillus, and inverse associations for Adlercreutzia, Ruminococcus, and Intestinibacter. Importantly, the associations of most species, especially Adlercreutzia and Ruminococcus, were largely independent of antidiabetic medications use. Meanwhile, 18 proteins and 76 metabolites, including 3 microbially derived metabolites (trimethylamine N-oxide, phenylacetylglutamine (PAGln), imidazolepropionic acid (IMP)), 50 lipids (e.g., diradylglycerols (DGs) and triradylglycerols (TGs)) and 23 non-lipid metabolites, were associated with diabetes (FDR-q < 0.1), with the majority showing positive associations and more than half of them (59/76) associated with incident diabetes. In mediation analyses, several proteins, especially interleukin-18 receptor 1 and osteoprotegerin, IMP and PAGln partially mediate the observed bacterial genera-diabetes associations, particularly for those of Adlercreutzia and Escherichia. Many diabetes-associated metabolites and proteins were altered in HIV, but no effect modification on their associations with diabetes was observed by HIV. CONCLUSION: Among individuals with and without HIV, multiple gut bacterial genera, blood metabolites, and proinflammatory proteins were associated with diabetes. The observed mediated effects by metabolites and proteins in genera-diabetes associations highlighted the potential involvement of inflammatory and metabolic perturbations in the link between gut dysbiosis and diabetes in the context of HIV infection.

Personality systems interactions theory: an integrative framework complementing the study of the motivational and volitional dynamics underlying adjustment to chronic pain.

In the endeavor to advance our understanding of interindividual differences in dealing with chronic pain, numerous motivational theories have been invoked in the past decade. As they focus on relevant, yet different aspects of the dynamic, multilevel processes involved in human voluntary action control, research findings seem fragmented and inconsistent. Here we present Personality Systems Interactions theory as an integrative meta-framework elucidating how different motivational and volitional processes work in concert under varying contextual conditions. PSI theory explains experience and behavior by the relative activation of four cognitive systems that take over different psychological functions during goal pursuit. In this way, it may complement existing content-related explanations of clinical phenomena by introducing a functional, third-person perspective on flexible goal management, pain acceptance and goal maintenance despite pain. In line with emerging evidence on the central role of emotion regulation in chronic pain, PSI theory delineates how the self-regulation of positive and negative affect impacts whether behavior is determined by rigid stimulus-response associations (i.e., habits) or by more abstract motives and values which afford more behavioral flexibility. Along with testable hypotheses, multimodal interventions expected to address intuitive emotion regulation as a central process mediating successful adaptation to chronic pain are discussed.

Bayesian Regression Facilitates Quantitative Modeling of Cell Metabolism.

This paper presents Maud, a command-line application that implements Bayesian statistical inference for kinetic models of biochemical metabolic reaction networks. Maud takes into account quantitative information from omics experiments and background knowledge as well as structural information about kinetic mechanisms, regulatory interactions, and enzyme knockouts. Our paper reviews the existing options in this area, presents a case study illustrating how Maud can be used to analyze a metabolic network, and explains the biological, statistical, and computational design decisions underpinning Maud.

Tagging the tjp1a Gene in Zebrafish with Monomeric Red Fluorescent Protein Using Biotin Homology Arms.

Tjp1a and other tight junction and adherens proteins play important roles in cell-cell adhesion, scaffolding, and forming seals between cells in epithelial and endothelial tissues. In this study, we labeled Tjp1a of zebrafish with the monomeric red fluorescent protein (mRFP) using CRISPR/Cas9-mediated targeted integration of biotin-labeled polymerase chain reaction (PCR) generated templates. Labeling Tjp1a with RFP allowed us to follow membrane and junctional dynamics of epithelial and endothelial cells throughout zebrafish embryo development. For targeted integration, we used short 35 bp homology arms on each side of the Cas9 genomic target site at the C-terminal of the coding sequence in tjp1a. Through PCR using 5' biotinylated primers containing the homology arms, we generated a double-stranded template for homology directed repair containing a flexible linker followed by RFP. Cas9 protein was complexed with the tjp1a gRNA before mixing with the repair template and microinjected into one-cell zebrafish embryos. We confirmed and recovered a precise integration allele at the desired site at the tjp1a C-terminus. Examination of fluorescence reveals RFP cell-cell junctional labeling using confocal imaging. We are currently using this stable tjp1a-mRFPis86 line to examine the behavior and interactions between cells during vascular formation in zebrafish.

Psychological and physical factors related to social integration of older adults in Ghana.

BACKGROUND: Globally, older adults aged 60 years and over are outnumbering children under 5 and young people aged 15-24. Much evidence exists on the importance of high social integration and positive quality of life and health outcomes. However, evidence on how older adults are socially integrated in Ghanaian communities is limited. This study examined how self-reported well-being and quality of life (psychological and physical (psycho-physical) factors) predict the social integration of older adults in Ghana. METHODS: A secondary analysis of longitudinal survey data of the 2014/15 Study on Global Ageing and Adult Health (SAGE Wave 2) conducted by the World Health Organization was applied. Older adults aged 60 years and older (n = 1,927) were included in this study. Multilevel logistic regression analyses were used to examine psycho-physical factors associated with high social integration among older adults. The output was reported as odds ratios (OR). RESULTS: In general, social integration varied based on older adults' demographic characteristics. Those in rural communities had lower odds of having high social integration (OR = 0.76, 95% CI = 0.56,1.03) when compared with older adults in urban areas. Having high physical and psychological well-being was associated with high social integration (OR = 1.90, 95% CI = 1.41, 2.57), (OR = 2.05, 95% CI = 1.56, 2.69). However, older adults with high levels of emotional and spiritual well-being were 9% and 7% (respectively) less likely to experience a high level of social integration (OR = 0.94, 95% CI = 0.71,1.24), (OR = 0.79, 95% CI = 0.60,1.04). CONCLUSION: The higher the level of self-reported psychological and physical well-being, the higher the social integration for older adults aged 60 years and over. However, the higher the level of self-reported emotional well-being and spiritual well-being, the less likely to have high social integration. Improved social integration or participation in society for older adults with high emotional and spiritual well-being is needed. The findings of this study highlight the need for policymakers and stakeholders to consider psycho-physical factors as an important public health tool and metric to encourage more research on the well-being of older adults in Ghana.

Housing and health for people from refugee and asylum-seeking backgrounds: findings from an Australian qualitative longitudinal study.

BACKGROUND: For people from asylum-seeking and refugee backgrounds, housing and the re-establishment of home are key social determinants of health. Research highlights the inequities faced by asylum seekers and refugees in the housing markets of high-income resettlement countries, resulting in their overrepresentation in precarious housing. There is also emerging evidence of the relationship between housing and health for this population relating to lack of affordability, insecurity of tenure, and poor suitability (physical and social). The mechanisms by which housing impacts health for this group within these housing contexts, is however, understudied - especially overtime. This qualitative longitudinal study aimed to address this gap. METHODS: Semi-structured interviews were conducted with 25 people from asylum-seeking and refugee backgrounds in South Australia, recruited through a community survey. Thematic analysis of interview data across three time points over three years identified four material and psychosocial mechanisms through which housing contributed to health outcomes via psychological and physical stressors - physical environment; stability; safety; and social connections, support and services. The study also identified additional health promoting resources, particularly elements of ontological security. The dynamics of these indirect and direct mechanisms were further illuminated by considering the impact of international, national and local contexts and a range of intersecting social factors including gender, country/culture of origin, family circumstances, immigration status, language skills, income, and health status. CONCLUSIONS: Rebuilding a sense of home and ontological security is a key resettlement priority and crucial for wellbeing. More comprehensive strategies to facilitate this for refugees and asylum seekers are required.

Factors influencing integration of mental health screening and treatment at HIV clinic settings in Cameroon: a qualitative study of health providers' perspectives.

BACKGROUND: Mental disorders are common among people with HIV (PWH) and are associated with poor HIV outcomes. Despite high unmet mental health needs among PWH, use of evidence-based mental health screening and treatment protocols remains limited at HIV treatment facilities across low-resource settings. Integrating mental health services into HIV care can reduce this gap. This study's objective was to explore factors that influence integration of mental health screening and treatment into HIV clinics in Cameroon. METHODS: We analyzed 14 in-depth interviews with clinic staff supporting PWH at three urban HIV treatment clinics in Cameroon. Interviews focused on current processes, barriers and facilitators, and types of support needed to integrate mental health care into HIV care. Interviews were recorded and transcribed. French transcripts were translated into English. We used thematic analysis to identify factors that influence integration of mental health screening and treatment into HIV care in these settings. Ethical review boards in the United States and Cameroon approved this study. RESULTS: Respondents discussed a lack of standardized mental health screening processes in HIV treatment facilities and generally felt ill-equipped to conduct mental health screening. Low community awareness about mental disorders, mental health-related stigma, limited physical space, and high clinic volume affected providers' ability to screen clients for mental disorders. Providers indicated that better coordination and communication were needed to support client referral to mental health care. Despite these barriers, providers were motivated to screen clients for mental disorders and believed that mental health service provision could improve quality of HIV care and treatment outcomes. All providers interviewed said they would feel more confident screening for mental disorders with additional training and resources. Providers recommended community sensitization, training or hiring additional staff, improved coordination to manage referrals, and leadership buy-in at multiple levels of the health system to support sustainable integration of mental health screening and treatment into HIV clinics in Cameroon. CONCLUSIONS: Providers reported enthusiasm to integrate mental health services into HIV care but need more support and training to do so in an effective and sustainable manner.

Quantifying soil microbial effects on plant species coexistence: A conceptual synthesis.

Soil microorganisms play a critical role in shaping the biodiversity dynamics of plant communities. These microbial effects can arise through direct mediation of plant fitness by pathogens and mutualists, and over the past two decades, numerous studies have shined a spotlight on the role of dynamic feedbacks between plants and soil microorganisms as key determinants of plant species coexistence. Such feedbacks occur when plants modify the composition of the soil community, which in turn affects plant performance. Stimulated by a theoretical model developed in the 1990s, a bulk of the empirical evidence for microbial controls over plant coexistence comes from experiments that quantify plant growth in soil communities that were previously conditioned by conspecific or heterospecific plants. These studies have revealed that soil microbes can generate strong negative to positive frequency-dependent dynamics among plants. Even as soil microbes have become recognized as a key player in determining plant coexistence outcomes, the past few years have seen a renewed interest in expanding the conceptual foundations of this field. New results include re-interpretations of key metrics from classic two-species models, extensions of plant-soil feedback theory to multispecies communities, and frameworks to integrate plant-soil feedbacks with processes like intra- and interspecific competition. Here, I review the implications of theoretical developments for interpreting existing empirical results and highlight proposed analyses and designs for future experiments that can enable a more complete understanding of microbial regulation of plant community dynamics.

Increased functional integration of emotional control network in late adulthood.

Across the adult lifespan, there are changes in how emotions are perceived and regulated. As individuals age, there is an observed improvement in emotion regulation and overall quicker recovery from negative emotions. While previous studies have shown differences in emotion processing in late adulthood, the corresponding differences in large-scale brain networks remain largely underexplored. By utilizing large-scale datasets such as the Human Connectome Project (HCP-Aging, N=621) and Cambridge Centre for Ageing and Neuroscience (Cam-CAN, N=333), we were able to investigate how emotion regulation networks' functional topography differs across the entire adult lifespan. Based on previous meta-analytic work that identified four large-scale functional brain networks involved in emotion generation and regulation, we found an increase in the functional integration of the emotional control network among older adults. Additionally, confirming through the nonlinear model, individuals around the age of 70 showed a steadier decline in integration of a network mediating emotion generation and regulation via interoception. Furthermore, the analyses revealed a negative association between age and perceived stress and loneliness that could be attributed to differences in large-scale emotion regulation networks. Our study highlights the importance of identifying topological changes in the functional emotion network architecture across the lifespan, as it allows for a better understanding of emotional aging and psychological well-being in late adulthood.

Measurement and spatial correlation analysis of high-quality development Level: A case study of the Yangtze River Delta urban agglomeration in China.

Against the backdrop of slowing economic growth and increasing environmental pressure, the Yangtze River Delta city cluster, as one of the largest city clusters in the world, has become more driven in its pursuit of high-quality development. We constructed a system of 24 evaluation indexes and used entropy-weighted TOPSIS to calculate and study the high-quality development index of urban agglomerations in the region. First, the level of high quality development (HQD) of the Yangtze River Delta city cluster generally improved from 2010 to 2021, with 2017 was the best year, while 2010 was the worst year. Second, in the multidimensional evaluation of HQD, Jiangsu excels in innovation and people's livelihood with 0.524 and 0.534, respectively; Shanghai (0.531) excels in coordinated development; Zhejiang excels in green and economic development with 0.557 and 0.484, respectively; and Anhui lags behind in all aspects. Third, the development process of HQD in the Yangtze River Delta region is uneven, and the level of HQD development varies greatly among the city clusters in the province. The measurement results show that Shanghai (0.511) has the highest score, followed by Zhejiang (0.484), Jiangsu (0.440) and Anhui (0.435). Fourth, spatial correlation analysis shows that Shanghai and Jiangsu are mainly distributed in the double-high region, Zhejiang is distributed in the high-low region, while Anhui is concentrated in the low-low region. The results of this study help us understand more deeply the characteristics and challenges of high-quality development in the Yangtze River Delta urban agglomerations and provide a scientific basis for more precise urban development policies.