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Structure and unusual binding mechanism of the hyaluronan receptor LYVE-1 mediating leucocyte entry to lymphatics
Get PDFImmune surveillance involves the continual migration of antigen-scavenging immune cells from the tissues to downstream lymph nodes via lymphatic vessels. To enable such passage, cells first dock with the lymphatic entry receptor LYVE-1 on the outer surface of endothelium, using their endogenous hyaluronan glycocalyx, anchored by a second hyaluronan receptor, CD44. Why the process should require two different hyaluronan receptors and by which specific mechanism the LYVE-1•hyaluronan interaction enables lymphatic entry is however unknown. Here we describe the crystal structures and binding mechanics of murine and human LYVE-1•hyaluronan complexes. These reveal a highly unusual, sliding mode of ligand interaction, quite unlike the conventional sticking mode of CD44, in which the receptor grabs free hyaluronan chain-ends and winds them in through conformational re-arrangements in a deep binding cleft, lubricated by a layer of structured waters. Our findings explain the mode of action of a dedicated lymphatic entry receptor and define a distinct, low tack adhesive interaction that enables migrating immune cells to slide through endothelial junctions with minimal resistance, while clinging onto their hyaluronan glycocalyx for essential downstream functions
Gendered impacts of climate change on integrated crop-dairy goat farming in Kenya
Get PDFAgriculture is the economic engine of Kenyan economy since it contributes to about 24% of the real GDP. However, its contribution has significantly reduced due to climate change that has impacted negatively crop production, pasture, and animals. A cross-sectional survey was undertaken among 201 households in Endo ward, Elgeyo Marakwet County to understand the effects of climate change and feed diversity. Climate change has profoundly affected individuals along the integrated value chain, with unreliable rainfall being the most significant issue, reported by 99.5% of respondents. Contrastingly, floods during the rainy season were experienced by 15.9%, while pests and diseases were reported by only 1.5% of respondents. The findings highlight a significant gender disparity in the impact of climate change along the integrated value chain resulting in shifts and challenges that impact women, men, and youth in distinct ways. Women, particularly those over 35 years, face severe consequences such as food shortages and malnutrition (56.2%), and loss of lives due to environmental disasters (39.8%). Young females bear increased domestic responsibilities, including fetching water (86.6%), which intensifies during periods of climate stress. Men over 35 years reported substantial economic losses and the impact on agricultural productivity due to pests and diseases. Although younger males are affected, their experiences are less severe compared to older males and females. In the context of dairy goat farming, there is a gender-based specialization of tasks. Men over 35 years predominantly handle activities such as shed construction (60%), marketing (54.2%), pest and disease control (57.2%), enterprise decision-making (58.7%), breeding (58.7%), and slaughtering (64.7%). Younger males, those under 35 years, are primarily responsible for transportation (62.2%). On the other hand, women under 35 are actively involved in feeding the goats (62.7%), cleaning the sheds (57.7%), and providing water (56.7%), with a notable focus on this younger age group of women. The study underscores the need for gender-sensitive adaptation strategies to address the differentiated impacts of climate change. By understanding the specific challenges faced by various demographic groups, policymakers and development practitioners can design more effective interventions to build resilience, and ensure equitable outcomes along the integrated farming system
Challenges for people with depression in using online mental health communities (OMHCs) in Saudi Arabia
Get PDFDepression is one of the most prevalent mental health illnesses and a significant public health concern in Saudi Arabia. Due to misconceptions about mental health diseases, such as depression, in Saudi Arabia, there is widespread stigma. Many people with depression, therefore, seek health information via social
media such as blogs, microblogs, and online communities. Online mental health communities (OMHCs) have been developed only recently in the country. This study explores the challenges people experience when engaging in OMHCs. A sample of 1,422 posts was generated from two OMHCs and analyzed using inductive thematic analysis. Three main themes were identified: misinformation, triggering vulnerability, and judgment. Findings from this study will be shared with the OMHCs and will help administrators to develop strategies and policies to enhance the experience of people with depression in using OMHCs
Gender inequality and cultural values in explaining gender differences in positive and negative emotions: a comparison of 24 countries during the COVID-19 pandemic
Get PDFThe coronavirus pandemic posed a major challenge to mental health. Existing evidence shows that COVID-19 is related to poor emotional well-being, particularly among women. However, most work on the subject uses single-country samples, limiting the ability to generalize the disparity or explain it as a function of societal variables. The present study investigates the expression of positive and negative emotions during the pandemic as a function of gender and across 24 countries (N = 49,637). Strong gender differences emerged across countries, with women reporting more negative emotions (anxious, depressed, nervous, exhausted) and less positive emotions (calm, content, relaxed, energetic) than men. The gender gap in positive emotions was significantly wider in countries higher in individualism and narrower in countries higher in power distance. For instance, differences in emotions were larger in Western countries high in individualism, such as the USA, the UK, Italy, and France, and smaller in countries with higher collectivism and power distance, such as China, Malaysia, and South Korea, with a few exceptions like Japan and Brazil. These gender differences across countries were not explained by country-level gender inequalities indicators (GGGI and GII). Interestingly, the national severity of the pandemic, an epidemiological factor, reduced gender differences in positive emotions. These results underscore the importance of considering cultural and national factors when assessing gender differences in well-being
Assessing the value for money, from a policy maker perspective, of 24 randomised controlled trial designs for an online weight maintenance guided self-help intervention: an expected value of sample information analysis
Get PDFObjective
To analyse whether conducting a randomised controlled trial (RCT) to evaluate an online weight maintenance guided self-help intervention (Supporting Weight Management (SWiM)) would offer good value for money in the United Kingdom.
Method
We examined 24 RCT designs by varying inclusion criteria (participants completing behavioural weight management, specialist-led weight management, diabetes prevention programme, type 2 diabetes remission, digital weight management, all weight management services), trial duration (1–2 years), and sample size (n = 500 or 2000). Trial benefits were estimated by the method of expected value of sample information analysis using a health economic model. The model examines how the proposed intervention affects weight maintenance over time (with uncertainty), and generates estimated lifetime Quality Adjusted Life Years (QALYs) and National Health Service (NHS) costs. Structured expert elicitation with 4 experts was undertaken to quantify pre-trial uncertainty in the effectiveness of SWiM compared with usual care. All trial designs were simulated to estimate trial benefits: the reduction in the costs of an inefficient decision for future populations over 10 years. Trial designs offer value for money if trial benefits exceed trial costs.
Results
For three inclusion criteria options (groups recently completing ‘diabetes remission’, ‘digital weight management’ or ‘specialist weight management’), the cost of the proposed trials was estimated to exceed the estimated trial benefit (value of the reduction in decision uncertainty) over 10 years. For the other three inclusion criteria options (groups recently completed ‘behavioural weight management’, ‘diabetes prevention programme’, or ‘all weight loss programmes’), 12 trial designs produced greater benefits than costs. The optimal trial design option would include ‘all weight loss programmes’, with 2 years follow-up and sample size n = 2000.
Conclusion
Investment in a large RCT to evaluate the SWiM intervention for patients completing a range of weight loss interventions offers the greatest value to the NHS
Exploring mechanisms of behavior change for healthcare professionals in cough and secretion management in ALS
Get PDFObjectives
To explore healthcare professionals’ experiences managing cough and secretion problems in Amyotrophic Lateral Sclerosis (ALS).
Methods
A qualitative study was completed with 23 individuals participating in four focus groups. Data was analyzed using reflexive thematic analysis and COM-B and theoretical domains framework (TDF) behavior change frameworks.
Results
This study found that roles, responsibilities, and expectations needed to be clearly defined and that building relationships was important to support care delivery. Barriers identified included limited access to specialist care, equipment, and opportunities to gain knowledge and skills. A structured clinical assessment was highlighted to enable good-quality care. Data mapped most commonly to the environmental context/resources, knowledge, skills (TDF), and physical capability (COM-B) behavior change domains.
Conclusion
Cough and secretion management in ALS is complex due to the multifaceted nature of the disease. This study emphasizes the need for future development of clinical interventions to support care
PLS-SEM and reflective constructs: A response to recent criticism and a constructive path forward
Get PDFThis article addresses criticisms asserting that reflective construct measurement and its associated evaluation criteria are unsuitable for partial least squares structural equation modeling (PLS-SEM). More specifically, critics contend that reflective measurement models correspond exclusively to common factor models, a premise that is both inaccurate and misleading. Reflective measurement models represent theoretically grounded and conceptualized constructs. Statistical methods such as common factor model estimation, composite model estimation, and sum score regression enable researchers to estimate method-specific proxies that serve as approximations for theoretically established conceptual constructs in empirical research. These proxies vary depending on the statistical models and assumptions inherent to each method. In this context, it is important to highlight that the use of reflective evaluation criteria is not restricted to common factor models. When applied to composite model estimation, it does not compromise the validity of the results. Moreover, this article advocates for embracing the complementary strengths of diverse SEM methods within a multimethod approach, rather than positioning one method in opposition to another. We believe that this contribution provides critical insights and guidance, fostering advancements in SEM methodology, and its practical applications
Electro-mechanical insights into the mixing of conductive and non-conductive sands at an interface
Get PDFThis paper investigates the electrical behaviour of an electrically conductive sand particle when mixed with non-conductive silica sand, commonly used in the railway industry. Laboratory tests and numerical simulations are conducted to assess the effect of mixing on the electrical conduction properties at the metal-to-metal interface under mechanical loading. Results from compression tests demonstrate that mixing with even 5 % mass of conductive particles can significantly reduce electrical resistance at the interface; however, the decrease in electrical resistance gradually slows down when the mixing ratio of conductive particles exceeds 10 %. Discrete element modelling of high pressure torsion tests – enhanced with a newly proposed electro-mechanical contact model – reveal that fine conductive particles are more effective than coarse particles in reducing interfacial electrical resistance at equal mixing ratios. A heatmap is proposed to estimate the percentage of conductive particles required to bring the resistance of the interface below the critical threshold of 10 Ω for track circuit, which links the resistivity of various conductive particles with their required mixing ratio
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