Arabidopsis immune responses triggered by cellulose- and mixed-linked glucan-derived oligosaccharides require a group of leucine-rich repeat malectin receptor kinases.

The plant immune system perceives a diversity of carbohydrate ligands from plant and microbial cell walls through the extracellular ectodomains (ECDs) of pattern recognition receptors (PRRs), which activate pattern-triggered immunity (PTI). Among these ligands are oligosaccharides derived from mixed-linked ß-1,3/ß-1,4-glucans (MLGs; e.g. ß-1,4-D-(Glc)2 -ß-1,3-D-Glc, MLG43) and cellulose (e.g. ß-1,4-D-(Glc)3 , CEL3). The mechanisms behind carbohydrate perception in plants are poorly characterized except for fungal chitin oligosaccharides (e.g. ß-1,4-d-(GlcNAc)6 , CHI6), which involve several receptor kinase proteins (RKs) with LysM-ECDs. Here, we describe the isolation and characterization of Arabidopsis thaliana mutants impaired in glycan perception (igp) that are defective in PTI activation mediated by MLG43 and CEL3, but not by CHI6. igp1-igp4 are altered in three RKs - AT1G56145 (IGP1), AT1G56130 (IGP2/IGP3) and AT1G56140 (IGP4) - with leucine-rich-repeat (LRR) and malectin (MAL) domains in their ECDs. igp1 harbors point mutation E906K and igp2 and igp3 harbor point mutation G773E in their kinase domains, whereas igp4 is a T-DNA insertional loss-of-function mutant. Notably, isothermal titration calorimetry (ITC) assays with purified ECD-RKs of IGP1 and IGP3 showed that IGP1 binds with high affinity to CEL3 (with dissociation constant KD  = 1.19 ± 0.03 µm) and cellopentaose (KD  = 1.40 ± 0.01 µM), but not to MLG43, supporting its function as a plant PRR for cellulose-derived oligosaccharides. Our data suggest that these LRR-MAL RKs are components of a recognition mechanism for both cellulose- and MLG-derived oligosaccharide perception and downstream PTI activation in Arabidopsis.

Motor cortical inactivation impairs corrective submovements in mice performing a hold-still center-out reach task.

Holding still and aiming reaches to spatial targets may depend on distinct neural circuits. Using automated homecage training and a sensitive joystick, we trained freely-moving mice to contact a joystick, hold their forelimb still, and then reach to rewarded target locations. Mice learned the task by initiating forelimb sequences with clearly resolved submillimeter-scale micromovements followed by millimeter-scale reaches to learned spatial targets. Hundreds of thousands of trajectories were decomposed into millions of kinematic submovements, while photoinhibition was used to test roles of motor cortical areas. Inactivation of both caudal and rostral forelimb areas preserved the ability to produce aimed reaches, but reduced reach speed. Inactivation specifically of contralateral caudal forelimb area (CFA) additionally impaired the ability to aim corrective submovements to remembered locations following target undershoots. Our findings show that motor cortical inactivations reduce the gain of forelimb movements but that inactivation specifically of contralateral CFA impairs corrective movements important for reaching a target location.

Influence of gaze, vision, and memory on hand kinematics in a placement task.

People usually reach for objects to place them in some position and orientation, but the placement component of this sequence is often ignored. For example, reaches are influenced by gaze position, visual feedback, and memory delays, but their influence on object placement is unclear. Here, we tested these factors in a task where participants placed and oriented a trapezoidal block against two-dimensional (2-D) visual templates displayed on a frontally located computer screen. In experiment 1, participants matched the block to three possible orientations: 0° (horizontal), +45° and -45°, with gaze fixated 10° to the left/right. The hand and template either remained illuminated (closed-loop), or visual feedback was removed (open-loop). Here, hand location consistently overshot the template relative to gaze, especially in the open-loop task; likewise, orientation was influenced by gaze position (depending on template orientation and visual feedback). In experiment 2, a memory delay was added, and participants sometimes performed saccades (toward, away from, or across the template). In this task, the influence of gaze on orientation vanished, but location errors were influenced by both template orientation and final gaze position. Contrary to our expectations, the previous saccade metrics also impacted placement overshoot. Overall, hand orientation was influenced by template orientation in a nonlinear fashion. These results demonstrate interactions between gaze and orientation signals in the planning and execution of hand placement and suggest different neural mechanisms for closed-loop, open-loop, and memory delay placement.NEW & NOTEWORTHY Eye-hand coordination studies usually focus on object acquisition, but placement is equally important. We investigated how gaze position influences object placement toward a 2-D template with different levels of visual feedback. Like reach, placement overestimated goal location relative to gaze and was influenced by previous saccade metrics. Gaze also modulated hand orientation, depending on template orientation and level of visual feedback. Gaze influence was feedback-dependent, with location errors having no significant effect after a memory delay.

Multimodal convergence in the pedunculopontine tegmental nucleus: Motor, sensory and theta-frequency inputs influence activity of single neurons.

The pedunculopontine tegmental nucleus of the brainstem (PPTg) has extensive interconnections and neuronal-behavioural correlates. It is implicated in movement control and sensorimotor integration. We investigated whether single neuron activity in freely moving rats is correlated with components of skilled forelimb movement, and whether individual neurons respond to both motor and sensory events. We found that individual PPTg neurons showed changes in firing rate at different times during the reach. This type of temporally specific modulation is like activity seen elsewhere in voluntary movement control circuits, such as the motor cortex, and suggests that PPTg neural activity is related to different specific events occurring during the reach. In particular, many neuronal modulations were time-locked to the end of the extension phase of the reach, when fine distal movements related to food grasping occur, indicating strong engagement of PPTg in this phase of skilled individual forelimb movements. In addition, some neurons showed brief periods of apparent oscillatory firing in the theta range at specific phases of the reach-to-grasp movement. When movement-related neurons were tested with tone stimuli, many also responded to this auditory input, allowing for sensorimotor integration at the cellular level. Together, these data extend the concept of the PPTg as an integrative structure in generation of complex movements, by showing that this function extends to the highly coordinated control of the forelimb during skilled reach to grasp movement, and that sensory and motor-related information converges on single neurons, allowing for direct integration at the cellular level.

Ramucirumab for advanced hepatocellular carcinoma in the current real world: a Japanese single-arm study post-REACH-2 (The R-evolution study).

This study aimed to complement the results of the REACH-2 study by prospectively evaluating the safety and efficacy of ramucirumab in advanced hepatocellular carcinoma (HCC) in a real-world setting. This was an open-label, nonrandomized, multicenter, prospective study conducted at 13 institutions in Japan (jRCTs031190236). The study included Child-Pugh Class A patients with advanced HCC who had received pretreatment with atezolizumab plus bevacizumab (Atez/Bev) or lenvatinib. Ramucirumab was introduced as a second-line treatment after Atez/Bev or lenvatinib and as a third-line treatment after Atez/Bev and lenvatinib. Between May 2020 and July 2022, we enrolled 19 patients, including 17 who received ramucirumab. Additionally, seven patients received lenvatinib, another seven patients received Atez/Bev, and three patients received Atez/Bev followed by lenvatinib as prior treatment. The primary endpoint was a 6-month progression-free survival (PFS) rate, which was 14.3%. The median PFS and overall survival were 3.7 and 12.0 months, respectively. The most common grade ≥ 3 adverse events (AEs) were hypertension (23.5%), proteinuria (17.6%), and neutropenia (11.8%). The discontinuation rate due to AEs was 29.4%. Six patients progressed from Child-Pugh A to B after treatment with ramucirumab. Thirteen patients were eligible for post-ramucirumab treatment, including systemic therapy. Despite the limited number of patients, the efficacy of ramucirumab was comparable to that observed in the REACH-2 study when used after lenvatinib and Atez/Bev. However, the incidence of AEs was higher than that in the REACH-2 study.

Distinct Inhibitory-Control Processes Underlie Children's Judgments of Fairness.

We examined how 5- to 8-year-olds (N = 51; Mage = 83 months; 27 female, 24 male; 69% White, 12% Black/African American, 8% Asian/Asian American, 6% Hispanic, 6% not reported) and adults (N = 18; Mage = 20.13 years; 11 female, 7 male) accepted or rejected different distributions of resources between themselves and others. We used a reach-tracking method to track finger movement in 3D space over time. This allowed us to dissociate two inhibitory processes. One involved pausing motor responses to detect conflict between observed information and how participants thought resources should be divided; the other involved resolving the conflict between the response and the alternative. Reasoning about disadvantageous inequities involved more of the first system, and this was stable across development. Reasoning about advantageous inequities involved more of the second system and showed more of a developmental progression. Generally, reach tracking offers an on-line measure of inhibitory control for the study of cognition.

Grouping approaches based on structure alone are insufficient to conclude about toxicological properties-the example of monoamine-based chelates.

Aminocarboxylic acid (monoamine-based) chelating agents such as GLDA, MGDA, NTA, and EDG are widely used in a variety of products and processes. In the European Union, based on the Green Deal and the Chemicals Strategy for Sustainability (CSS), there is an increasing tendency to speed up chemical hazard evaluation and to regulate chemicals by grouping substances based on molecular structure similarity. Recently, it was proposed to group polycarboxylic acid monoamines, hydroxy derivatives and their salts with monovalent cations, and to consider all group members as potential carcinogens based on the official CLP classification of one group member, viz. NTA, which is classified as suspected carcinogen Cat. 2. In this review, we show that a grouping approach for harmonized classification and labeling based on molecular structure alone, disregarding existing animal test data as well as current scientific and regulatory knowledge, would result in incorrect classification. Using such a simplistic, although considered pragmatic approach, classification of all group members upfront would not improve protection of human health. Instead, it could not only lead to unnecessary additional vertebrate animal testing but also to onerous and disproportionate restrictions being placed on the use of these valuable substances; some of these even being considered as green chemicals.

Identifying and characterizing high-risk populations in pilot malaria elimination districts in Madagascar: a mixed-methods study.

BACKGROUND: In Madagascar, the districts of Antsirabe II, Faratsiho and Antsiranana I have relatively low malaria incidence rates and have been selected by the National Malaria Control Programme for pilot elimination strategies. The districts have residual transmission despite increasing coverage and quality of malaria services. This study sought to identify priority subpopulations at highest risk for malaria and collect information on intervention preferences and methods that will inform subnational tailoring of malaria service delivery. METHODS: This mixed methods study employed (i) a quantitative malaria risk factor assessment in Antsirabe II and Faratsiho comprising a test-negative frequency matched case-control study and a qualitative risk factor assessment in Antsiranana I; and (ii) a qualitative formative assessment in all three districts. For the case-control study, a mixed effects logistic regression was used with age, sex and district included as fixed effects and health facility included as a random effect. The qualitative risk factor assessment used semi-structured interview guides and key informant interviews. For the qualitative formative assessment in the three districts, a summary report was generated following semi-structured interviews and focus group discussions with high-risk populations (HRPs) and stakeholders. RESULTS: In Antsirabe II and Faratsiho districts, rice agriculture workers, outdoor/manual workers, particularly miners, and those with jobs that required travel or overnight stays, especially itinerant vendors, had higher odds of malaria infection compared to other (non-rice) agricultural workers. In Antsiranana I, respondents identified non-rice farmers, mobile vendors, and students as HRPs. Risk factors among these groups included overnight stays and travel patterns combined with a lack of malaria prevention tools. HRPs reported treatment cost and distance to the health facility as barriers to care and expressed interest in presumptive treatment and involvement of gatekeepers or people who have influence over intervention access or participation. CONCLUSIONS: The study results illustrate the value of in-depth assessments of risk behaviours, access to services and prevention tools, surveillance and prevention strategies, and the involvement of gatekeepers in shaping subnational tailoring to reach previously unreached populations and address residual transmission in elimination settings.

Post-error adjustments occur in both reaching and grasping.

Post-error slowing (PES), the tendency to slow down a behavioral response after a previous error, has typically been investigated during simple cognitive tasks using response time as a measure of PES magnitude. More recently, PES was investigated during a single reach-to-grasp task to determine where post-error adjustments are employed in a more ecological setting. Kinematic analyses in the previous study detected PES during pre-movement planning and within the grasping component of movement execution. In the current study (N = 22), we increased the cognitive demands of a reach-to-grasp task by adding a choice between target and distractor locations to further explore PES, and other post-error adjustments, under different task conditions. We observed a significant main effect of task condition on overall reaction time (RT); however, it did not significantly impact PES or other post-error adjustments. Nonetheless, the results of this study suggest post-error adjustment is a flexible process that can be observed during pre-movement planning and within the onset and magnitude of the reaching component, as well as in the magnitudes of the grasping component. Considering the sum of the results in the context of existing literature, we conclude that the findings add support to a functional account of error reactivity, such that post-error adjustments are implemented intentionally to improve performance.

Findings from the Promoting Independence in Dementia App (PRIDE-app) Study a Reach, Effectiveness, Adoption, Implementation, and Maintenance Framework Discussion.

INTRODUCTION: Self-management is pivotal in helping people with their independence and in managing their health conditions more effectively. The PRIDE-app is a novel online intervention, providing support and information for people living with dementia and their families, aimed at increasing self-management and improving quality of life. Knowledge generated will help inform future developments to the app, with the aim of improving its uptake and implementation in services. METHODS: A mixed-methods approach incorporating the RE-AIM framework. Recruited 25 people living with dementia, of which 17completed the PRIDE-app intervention over 8 weeks with support from a dementia adviser facilitator. Measures exploring mood, physical well-being, and quality of life were collected at baseline, 3 and 6 months and analysed through modelled analysis. Post-intervention interviews were conducted with participants and facilitators and analysed through thematic analysis. RESULTS: Quantitative results did not show significant improvements in participants' scores. Qualitative data showed that the PRIDE-app motivated people to reconnect socially and set individual goals for activities. Participants and facilitators identified areas for improvements to the app interface and delivery format. CONCLUSIONS: This study evaluated the PRIDE-app's reach, effectiveness and adoptability in the independence and quality of life of people living with dementia, as well as how it could be implemented and maintained within services. Pre- and post-intervention scores were inconclusive. Interviews provided positive feedback of the app's influence on peoples' activities and mood.

A comprehensive review on PFAS including survey results from the EFLM Member Societies.

OBJECTIVES: Per- and polyfluoroalkyl substances (PFASs) are a large class of synthetic chemicals widely used for their unique properties. Without PFAS, many medical device and in vitro diagnostic technologies would not be able to perform their intended purposes. Potential health risks associated with exposure to PFAS influence their use in IVD applications. This paper aims to assess the current situation concerning PFAS, including regulations and legislations for their use. It is important to know what happens to (PFAS) at the end of their lives in medical laboratories. METHODS: A survey was conducted in March 2023 to collect information on the potential emission and end-of-life of PFAS-containing medical technologies in the medical laboratories of the EFLM member societies. A series of questions were presented to the EFLM national societies and the results were documented. RESULTS: Eight respondents participated in the survey, representing EFLM member societies in seven different countries including hospital laboratories, university laboratories, and private laboratories. CONCLUSIONS: PFAS uses in MD and IVD are influenced by several factors, including evolving regulations, advances in technology, safety and efficacy of these substances. Advancements in analytical techniques may lead to more sensitive and precise methods for detecting and quantifying PFAS in biological samples, which can be essential for IVD applications related to biomarker analysis and disease diagnosis. Collaboration among regulatory agencies, industry, research institutions, hospitals, and laboratories on a global scale can aid in establishing harmonized guidelines and standards for the use of PFAS, ensuring consistency and safety within their applications.

Reaching the unheard: overcoming challenges in health research with hard-to-reach populations.

PURPOSE: Addressing obstacles such as logistical complexities, social stigma, and the impact of historical traumas is essential for the successful inclusion of underrepresented groups in health research. METHODS: This article reviews engagement and interview techniques used to ethically engage recently settled Afghan refugees in Oklahoma and rural Mexican-born women in Illinois in research. The paper concludes with a reflective discussion on the challenges and lessons learned. RESULTS: Creative strategies to engage hard-to-reach populations in research included considering the participants' socioeconomic and cultural contexts in their interactions and developing community partnerships to establish trust and obtain reliable data. Other engagement strategies were communicating in the participants' preferred language, providing assistance with reading and responding to study questions for those with low literacy, employing research staff from the population of interest, and recruiting in specific locations where the populations of interest live. CONCLUSIONS: Community engagement is essential at all stages of research for building trust in hard-to-reach populations, achieving inclusivity in health research, and ensuring that interventions are culturally sensitive and effective.

The Development and the Assessment of Sampling Methods for Hard-to-Reach Populations in HIV Surveillance.

Due to stigma or legal issues, populations with higher HIV risk are often hard to reach, which impedes accurate population estimation of HIV burden. To better sample hard-to-reach populations (HTRPs) for HIV surveillance, various sampling methods have been designed and/or used since HIV epidemic following the first reported AIDS cases in 1981. This paper describes the development and the assessment (i.e., validity and reproducibility) of approximately eight sampling methods (e.g., convenience sampling, snowball sampling, time location sampling, and respondent-driven sampling) for HTRPs in HIV surveillance, with a focus on respondent-driven sampling (RDS). Compared to other methods, RDS has been greatly assessed. However, current evidence is still inadequate for RDS to be considered the best option for sampling HTRPs. The field must continue to assess RDS and to develop new sampling approaches or modifications to existing approaches.

Management of fetuses with apparent normal growth and abnormal cerebroplacental ratio: A risk-based approach near term.

INTRODUCTION: Cerebroplacental ratio (CPR) has been shown to be an independent predictor of adverse perinatal outcome at term and a marker of failure to reach the growth potential (FRGP) regardless of fetal size, being abnormal in compromised fetuses with birthweight above the 10th centile. The main aim of this study was to propose a risk-based approach for the management of pregnancies with normal estimated fetal weight (EFW) and abnormal CPR near term. MATERIAL AND METHODS: This was a retrospective study of 943 pregnancies, that underwent an ultrasound evaluation of EFW and CPR at or beyond 34 weeks. CPR values were converted into multiples of the median (MoM) and EFW into centiles according to local references. Pregnancies were then divided into four groups: normal fetuses (defined as EFW ≥10th centile and CPR ≥0.6765 MoM), small for gestational age (EFW <10th centile and CPR ≥0.6765 MoM), fetal growth restriction (EFW <10th centile and CPR <0.6765 MoM), and fetuses with apparent normal growth (EFW ≥10th centile) and abnormal CPR (<0.6765 MoM), that present FRGP. Intrapartum fetal compromise (IFC) was defined as an abnormal intrapartum cardiotocogram or pH requiring cesarean delivery. Risk comparisons were performed among the four groups, based on the different frequencies of IFC. The risks of IFC were subsequently extrapolated into a gestational age scale, defining the optimal gestation to plan the birth for each of the four groups. RESULTS: Fetal growth restriction was the group with the highest frequency of IFC followed by FRGP, small for gestational age, and normal groups. The "a priori" risks of the fetal growth restriction and normal groups were used to determine the limits of two scales. One defining the IFC risk and the other defining the appropriate gestational age for delivery. Extrapolation of the risk between both scales placed the optimal gestational age for delivery at 39 weeks of gestation in the case of FRGP and at 40 weeks in the case of small for gestational age. CONCLUSIONS: Fetuses near term may be evaluated according to the CPR and EFW defining four groups that present a progressive risk of IFC. Fetuses in pregnancies complicated by FRGP are likely to benefit from being delivered at 39 weeks of gestation.

Utility of in vivo metabolomics to support read-across for UVCB substances under REACH.

Structure-based grouping of chemicals for targeted testing and read-across is an efficient way to reduce resources and animal usage. For substances of unknown or variable composition, complex reaction products, or biological materials (UVCBs), structure-based grouping is virtually impossible. Biology-based approaches such as metabolomics could provide a solution. Here, 15 steam-cracked distillates, registered in the EU through the Lower Olefins Aromatics Reach Consortium (LOA), as well as six of the major substance constituents, were tested in a 14-day rat oral gavage study, in line with the fundamental elements of the OECD 407 guideline, in combination with plasma metabolomics. Beyond signs of clinical toxicity, reduced body weight (gain), and food consumption, pathological investigations demonstrated the liver, thyroid, kidneys (males only), and hematological system to be the target organs. These targets were confirmed by metabolome pattern recognition, with no additional targets being identified. While classical toxicological parameters did not allow for a clear distinction between the substances, univariate and multivariate statistical analysis of the respective metabolomes allowed for the identification of several subclusters of biologically most similar substances. These groups were partly associated with the dominant (> 50%) constituents of these UVCBs, i.e., indene and dicyclopentadiene. Despite minor differences in clustering results based on the two statistical analyses, a proposal can be made for the grouping of these UVCBs. Both analyses correctly clustered the chemically most similar compounds, increasing the confidence that this biological approach may provide a solution for the grouping of UVCBs.

Hard to reach? Methodological challenges researching vulnerable, gang-involved, young people.

INTRODUCTION: Research with young people (YP) is ethically challenging and bound in a complex maze of issues relating to power, voice and representation. Such sensitivities mean that the challenges raised in researching marginalised YP are often hard to navigate. This paper reports on research carried out with YP to explore links between mental health, school exclusion and involvement in criminal gangs. It aims to provide a practical guide to negotiating some of the methodological and ethical challenges experienced. METHOD: In-depth interviews conducted with 28 YP (aged 14-24 years) who were gang involved or seen to be at risk of gang involvement. Research was conducted in youth clubs, alternative provision and youth justice settings. RESULTS: OBSERVATIONS/REFLECTIONS: We reflect on how navigating ethics can create barriers to involving YP as primary informants in research. We consider why it is important to overcome these hurdles and how public engagement work with recognised gatekeepers and the use of creative interview methods can facilitate meaningful encounters, where YP feel able to share valuable insights into their lives. CONCLUSION: Alongside a number of specific learning points, the paper reflects on theories behind research with YP, including the need for recognition of power imbalances and reflexivity. It concludes with thoughts on the practical realities of achieving meaningful participation or an 'authentic voice' with marginalised groups and the importance of this in informing policy and practice. PATIENT OR PUBLIC CONTRIBUTION: The focus of this work was to collect experiences of YP who are recognised as gang-involved or at risk of being so, with a view to informing health and education policies. The scoping study for the project involved extensive public engagement work with YP exploring and trialling suitable methods of accessing, recruiting and ultimately interviewing this target group. This is central to the discussion within the body of the paper.

Health-related physical fitness, physical activity and its correlates among school going adolescents in hilly state in north India: a cross sectional survey.

INTRODUCTION: Health-related physical fitness, which includes body composition, cardiorespiratory fitness, muscular endurance, flexibility, power, and strength are associated with risks of chronic diseases and promote good health and wellness. There have been reports of increasing levels of physical inactivity among children and adolescents, leading to increasing rates of obesity and decreased physical fitness. The present study was conducted among school going adolescents to estimate the levels and correlates of PF for timely intervention. METHODOLOGY: School based cross-sectional study was done among students of class 8-11th in Government schools of Garhwal division of Uttarakhand. Multistage stratified random sampling was applied for recruitment of study participants. We recruited a final sample size of 634 students. Validated questionnaires and standard methods for assessment of physical fitness, physical activity levels and other variables such as waist circumference, hip circumference, BMI and hemoglobin estimation were done. RESULTS: Average and above average cardiorespiratory fitness score as per Harvard step test among boys (54.3%) was significantly higher as compared to girls (21.3%) (χ2 = 88.93, p < 0.001). There was a significant association between gender and dominant handgrip strength (χ2 = 8.02, p = 0.01) as well as between gender and Shoulder stretch test (SST) of dominant (χ2 = 17.5, p < 0.05) as well as nondominant arm (χ2 = 13.5, p < 0.05). Sit and reach test results also showed a significant association with gender (χ2 = 27.17, p < 0.001). Gender, hemoglobin level, BMI and PAL scores significantly predicted cardiorespiratory fitness scores (R2 = 0.188, F value of the model = 37.69, p =< 0.001)). CONCLUSION: Physical fitness of school going adolescents in Garhwal division of Uttarakhand was better than other parts of India, with significant gender differences. Physical activity levels (PAL) were poor and are also a significant predictor of physical fitness. More emphasis needs to be paid on the health and fitness of girl students. School based policies to increase PAL among students through innovation and rewards may go a long way in improving the long-term health of the students.

High prevalence of zero-dose children in underserved and special setting populations in Ethiopia using a generalize estimating equation and concentration index analysis.

BACKGROUND: Globally, according to the World Health Organization (WHO) 2023 report, more than 14.3 million children in low- and middle-income countries, primarily in Africa and South-East Asia, are not receiving any vaccinations. Ethiopia is one of the top ten countries contributing to the global number of zero-dose children. OBJECTIVE: To estimate the prevalence of zero-dose children and associated factors in underserved populations of Ethiopia. METHODS: A cross-sectional vaccine coverage survey was conducted in June 2022. The study participants were mothers of children aged 12-35 months. Data were collected using the CommCare application system and later analysed using Stata version 17. Vaccination coverage was estimated using a weighted analysis approach. A generalized estimating equation model was fitted to determine the predictors of zero-dose children. An adjusted odds ratio (AOR) with 95% confidence interval (CI) and a p-value of 0.05 or less was considered statistically significant. RESULTS: The overall prevalence of zero-dose children in the study settings was 33.7% (95% CI: 34.9%, 75.7%). Developing and pastoralist regions, internally displaced peoples, newly formed regions, and conflict-affected areas had the highest prevalence of zero-dose children. Wealth index (poorest [AOR = 2.78; 95% CI: 1.70, 4.53], poorer [AOR = 1.96; 95% CI: 1.02, 3.77]), single marital status [AOR = 2.4; 95% CI: 1.7, 3.3], and maternal age (15-24 years) [AOR = 1.2; 95% CI: 1.1, 1.3] were identified as key determinant factors of zero-dose children in the study settings. Additional factors included fewer than four Antenatal care visits (ANC) [AOR = 1.3; 95% CI: 1.2, 1.4], not receiving Postnatal Care (PNC) services [AOR = 2.1; 95% CI: 1.5, 3.0], unavailability of health facilities within the village [AOR = 3.7; 95% CI: 2.6, 5.4], women-headed household [AOR = 1.3; 95% CI:1.02, 1.7], low gender empowerment [AOR = 1.6; 95% CI: 1.3, 2.1], and medium gender empowerment [AOR = 1.7; 95% CI: 1.2, 2.5]. CONCLUSION: In the study settings, the prevalence of zero-dose children is very high. Poor economic status, disempowerment of women, being unmarried, young maternal age, and underutilizing antenatal or post-natal services are the important predictors. Therefore, it is recommended to target tailored integrated and context-specific service delivery approach. Moreover, extend immunization sessions opening hours during the evening/weekend in the city administrations to meet parents' needs.

Reliability and validity of the medial standing overhead arm reach (SOAR) test as a measure of functional hip adduction motion.

OBJECTIVE: The Posterior Standing Overhead Arm Reach (SOAR) test has been previously reported as a reliable clinical measure of closed chain hip extension motion. The proposed Medial SOAR test expands on that testing approach to provide a similar measure of functional hip adduction motion. This was a preliminary intrarater and interrater reliability and validity study of the Medial SOAR test as a measure of functional hip adduction. DESIGN: Cross-sectional. SETTING: University motion analysis laboratory. PARTICIPANTS: Fifty hips were assessed in 25 (22 female) asymptomatic participants (mean age = 23.4 years, SD = 0.8). MAIN MEASURES: Maximum hip adduction during the Medial SOAR test was measured with a standard goniometer independently by two examiners. The test was also performed using three-dimensional motion capture. The intrarater and interrater reliability of the goniometric measure was determined using intraclass correlation coefficients, and the relationship between measures obtained via goniometry and three-dimensional motion capture was assessed with Pearson correlations and Bland-Altman analysis. RESULTS: Intrarater reliability (ICC2,3) was 0.88 (95% CI = 0.80-0.92) for Examiner 1 and 0.87 (95% CI = 0.79-0.92) for Examiner 2. The standard error of measurement and minimal detectable change were less than 3.0°. Interrater reliability demonstrated an intraclass correlation coefficient = 0.62 (95% CI = 0.28-0.79). Pearson correlations were significant with low-to-moderate associations (r = 0.49, P < 0.001; r = 0.24, P = 0.045). CONCLUSIONS: Similar to the previously reported Posterior SOAR test, the Medial SOAR test demonstrated acceptable intrarater and interrater reliability, along with low-to-moderate associations with three-dimensional motion capture. The Medial SOAR test has the potential to provide a reliable and accurate assessment of closed chain hip adduction.

Can "Hazard-Cost-Effectiveness Analysis" improve the risk management of chemicals under REACH?

Cost-Effectiveness Analysis (CEA) is a decision-making framework to prioritize policy decisions for chemicals. Differences in hazard profiles among chemicals are not integrated in CEA under the EU REACH Regulation, which could limit its relevance. Another concern is that two different economic decision support methods (CEA for chemicals considered as PBTs or vPvBs from a regulatory perspective and Cost Benefit Analysis (CBA) for others) are used under REACH. To address this situation, we define "Hazard" CEA by integrating a hazard score, based on persistence, bioaccumulation and (eco)toxicity, in the effect indicator of CEA. We test different designs and parameterizations of Hazard-CEA on a set of past socio-economic assessments under REACH for PBT and non-PBT chemicals. Weighing and thresholds in hazard scores do not have a significant impact on the outcome of Hazard-CEA but the design of the hazard scoring method does. We suggest using an integrated and unweighted scoring method with a multiplicative formulation based on the notion of risk. Hazard-CEA could be used for both PBT and non-PBT chemicals, to use a single method in REACH and therefore improve consistency in policy decisions. Our work also suggests that using Hazard-CEA could help make decision easier.