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Children with congenital heart disease (CHD) can face neurodevelopmental, psychological, and behavioural difficulties beginning in infancy and continuing through adulthood. Despite overall improvements in medical care and a growing focus on neurodevelopmental screening and evaluation in recent years, neurodevelopmental disabilities, delays, and deficits remain a concern. The Cardiac Neurodevelopmental Outcome Collaborative was founded in 2016 with the goal of improving neurodevelopmental outcomes for individuals with CHD and pediatric heart disease. This paper describes the establishment of a centralised clinical data registry to standardize data collection across member institutions of the Cardiac Neurodevelopmental Outcome Collaborative. The goal of this registry is to foster collaboration for large, multi-centre research and quality improvement initiatives that will benefit individuals and families with CHD and improve their quality of life. We describe the components of the registry, initial research projects proposed using data from the registry, and lessons learned in the development of the registry.

BackgroundElderly people are particularly affected by rising systolic blood pressure (SBP). We hypothesized that resting blood pressure (RBP)-reducing isometric exercise training (IET) can be delivered in a group setting with older adults.MethodsParticipants (63–88 years; N = 19) completed IET at 30% maximum voluntary contraction, 3 days a week for 12 weeks. RBP was measured weekly throughout, plus 6 weeks posttraining. Control participants did not engage in IET (N = 5). Changes in RBP were assessed using a 2-way repeated-measures analysis of variance.ResultsIET induced significant reductions in SBP (−10.5 mmHg; P < 0.05), but SBP also declined unexpectedly in the control group (−4.5 mmHg; P < 0.05). Diastolic blood pressure declined in the IET group only (−4.7 mmHg; P < 0.05). There were no significant differences between groups for SBP or diastolic blood pressure (P > 0.05). At 6 weeks posttraining, SBP was still 9.4 mmHg below baseline in the IET group only. A unique finding was that the clinically significant RBP reductions persisted for 6 weeks after IET.ConclusionsHandgrip IET may be an effective antihypertensive intervention, which persists for several weeks in older adults, even when training ceases.

Bright debris discs can contain large amounts of CO gas. This gas was thought to be a protoplanetary remnant until it was recently shown that it could be released in collisions of volatile-rich solids. As CO is released, interstellar UV radiation photodissociates CO producing CI, which can shield CO allowing a large CO mass to accumulate. However, this picture was challenged because CI is inefficient at shielding if CO and CI are vertically mixed. Here, we study for the first time the vertical evolution of gas to determine how vertical mixing affects the efficiency of shielding by CI. We present a 1D model that accounts for gas release, photodissociation, ionisation, viscous evolution, and vertical mixing due to turbulent diffusion. We find that if the gas surface density is high and the vertical diffusion weak ($\alpha_{\rm v}/\alpha[H/r]^2$) CI and CO become well mixed, shortening the CO lifetime. Moreover, diffusion could also limit the amount of dust settling. High-resolution ALMA observations could resolve the vertical distribution of CO and CI, and thus constrain vertical mixing and the efficiency of CI shielding. We also find that the CO and CI scale heights may not be good probes of the mean molecular weight, and thus composition, of the gas. Finally, we show that if mixing is strong the CO lifetime might not be long enough for CO to spread interior to the planetesimal belt where gas is produced., Comment: Accepted for publication in MNRAS (18 pages, 14 figures)

Background: The World Health Organization acknowledges quality of life (QOL) as subjectively perceived overall well-being by the individual and recognizes it as an essential construct for overall health and wellness. The purpose of this study was to examine the association of infant, environmental, and parental factors with the QOL of mothers of infants at four months post-hospital discharge from cardiac surgery. Methods: Secondary analysis of prospectively collected data from the REACH randomized clinical trial of telehealth home monitoring. The sample included mothers (n = 148) of infants with congenital heart disease who provided data at four months post-discharge. Ten imputations were generated using fully conditional specification methods to address missing data and were combined. All analyses were performed on the imputed data. Mothers’ QOL was the main outcome of the analysis, as measured by the Ulm Quality of Life Inventory for Parents. Predictors on QOL were identified based on the World Health Organization QOL framework which recognizes the multidimensional domains influencing QOL that include personal factors, environmental factors, and physical factors related to disease and functioning. Results: The treatment and control groups did not differ on any study variable, thus data were collapsed and analyzed together. Final multivariable model found that the combination of dyadic adjustment, social support, parenting stress, and post-traumatic stress symptoms explained approximately three-quarters of the variance in QOL scores. Conclusions: QOL for mothers of infants with congenital heart disease is largely influenced by psychosocial factors. Future research targeted toward improving maternal QOL should include psychosocial interventions that address social networks and stress.

Objective:To assess the training and the future workforce needs of paediatric cardiac critical care faculty.Design:REDCap surveys were sent May−August 2019 to medical directors and faculty at the 120 US centres participating in the Society of Thoracic Surgeons Congenital Heart Surgery Database. Faculty and directors were asked about personal training pathway and planned employment changes. Directors were additionally asked for current faculty numbers, expected job openings, presence of training programmes, and numbers of trainees. Predictive modelling of the workforce was performed using respondents’ data. Patient volume was projected from US Census data and compared to projected provider availability.Measurements and main results:Sixty-six per cent (79/120) of directors and 62% (294/477) of contacted faculty responded. Most respondents had training that incorporated critical care medicine with the majority completing training beyond categorical fellowship. Younger respondents and those in dedicated cardiac ICUs were more significantly likely to have advanced training or dual fellowships in cardiology and critical care medicine. An estimated 49–63 faculty enter the workforce annually from various training pathways. Based on modelling, these faculty will likely fill current and projected open positions over the next 5 years.Conclusions:Paediatric cardiac critical care training has evolved, such that the majority of faculty now have dual fellowship or advanced training. The projected number of incoming faculty will likely fill open positions within the next 5 years. Institutions with existing or anticipated training programmes should be cognisant of these data and prepare graduates for an increasingly competitive market.

Stellar binaries represent a substantial fraction of stellar systems, especially among young stellar objects. Accordingly, binaries play an important role in setting the architecture of a large number of protoplanetary discs. Binaries in coplanar and polar orientations with respect to the circumbinary disc are stable configurations and could induce non-axisymmetric structures in the dust and gas distributions. In this work, we suggest that the structures shown in the central region of the protoplanetary disc HD 169142 are produced by the presence of an inner stellar binary and a circumbinary (P-type) planet. We find that a companion with a mass-ratio of 0.1, semi-major axis of 9.9 au, eccentricity of 0.2, and inclination of 90{\deg}, together with a 2 Jupiter Mass coplanar planet on a circular orbit at 45 au reproduce the structures at the innermost ring observed at 1.3 mm and the shape of spiral features in scattered light observations. The model predicts changes in the disc's dust structure, and star's astrometric parameters, which would allow testing its veracity by monitoring this system over the next 20 years., Comment: 11 pages, 7 figures, accepted for publication in MNRAS

Lung cancer maintains a relatively small survival rate (~19%) over a 5-year period and up to 80–85% of all lung cancer diagnoses are Non-Small Cell Lung Cancer (NSCLC). To determine whether metformin reduces non-small cell lung cancer (NSCLC) LL/2 cell growth, cells were grown in vitro and treated with metformin for 48 h. qPCR was used to assess genes related to cell cycle regulation and pro-apoptotic markers, namely Cyclin D, CDK4, p27, p21, and HES1. Treatment with 10 mM metformin significantly reduced HES1 expression (p = 0.011). Furthermore, 10 mM metformin treatment significantly decreased REDD1 (p = 0.0082) and increased p-mTOR Ser2448 (p = 0.003) protein expression. Control cells showed significant reductions in phosphorylated p53 protein expression (p = 0.0367), whereas metformin treated cells exhibited reduced total p53 protein expression (p = 0.0078). There were no significant reductions in AMPK, PKB/AKT, or STAT3. In addition, NSCLC cells were treated for 48 h. with 10 mM metformin, 4 µM gamma-secretase inhibitor (GSI), or the combination of metformin (10 mM) and GSI (4 µM) to determine the contribution of respective signaling pathways. Metformin treatment significantly reduced total nucleus expression of the proliferation maker Ki-67 with an above 65% reduction in Ki-67 expression between control and metformin-treated cells (p = 0.0021). GSI (4 µM) treatment significantly reduced Ki-67 expression by ~20% over 48 h (p = 0.0028). Combination treatment (10 mM metformin and 4 µM GSI) significantly reduced Ki-67 expression by more than 50% over 48 h (p = 0.0245). As such, direct administration of metformin (10 mM for 48 h) proved to be an effective pharmaceutical agent in reducing the proliferation of cultured non-small cell cancer cells. These intriguing in vitro results, therefore, support the further study of metformin in appropriate in vivo models as an anti-oncogenic agent and/or an adjunctive therapy.

Muscular flaps may represent a valid treatment option for prosthetic infection after knee arthroplasty.We present the results of 20 consecutive patients treated with the use of medial gastrocnemius flap for the management of different types of injuries or integumentary defects after total knee arthroplasty. Tissue necrosis or dehiscence occurred within 1 and 2 months after arthroplasty. The mean follow-up was 23.4 (12-60) months. Clinical outcome was evaluated according to the infection control rate and post-operative Knee Society Score (KSS).Prosthesis salvage and complete restoration of skin coverage were achieved in all patients. Functional assessment was performed using the KSS score. The final knee KSS score was classified as excellent (score: 80-100) in 0 patients, good (score: 70-79) in 17 patients, fair (score: 60-69) in 2 patients, and poor (score: 60) in 1 patient. Residual Extension Deficit: 0-20°; Very Satisfactory in 17 patients. 30-70° Satisfactory in 2 patients, 80-90° Unsatisfactory in 1 patient. Patients who successfully underwent flap treatment experienced a much greater increase in both components of the KSS score.The results highlight the effectiveness of medial gastrocnemius muscular flap for the treatment of prosthetic knee infection, in terms of function, limb salvage, cost-effectiveness and post-surgery quality of life. Further larger studies may consolidate these findings.

Proximal periprosthetic femoral fractures (PPFFs) are gradually increasing and surgical management is often associated with high risk of complications, due to elderly population and associated comorbidities.We retrospectively assessed 39 patients at least at 2-years follow-up. We identified two study groups, similar for demographic data. Group A included patients surgically treated without involving prosthetic implants, whereas Group B included patients in which an implant revision was performed.Data were recorded from January 2017 to February 2020, and 39 patients were included: 30 females (76.9%) and 9 males (23.1%), with a confirmed diagnosis of periprosthetic fracture of the proximal femur. 23 (58.9%) patients were treated with Open Reduction and Internal Fixation (ORIF), 12 (30.7%) with revision surgery and 4 (10.3%) were treated by modular megaprosthesis.The treatment options considered in the study, revision arthroplasty and internal fixation had shown no significant differences as a matter of clinical outcomes and postoperative complications.

Background Cardiovascular health (CVH) is suboptimal in US adolescents. Social determinants of health (SDOH) may affect CVH. We examined SDOH by race and ethnicity and assessed for associations between SDOH and CVH among US adolescents. Methods and Results We analyzed data from the National Health and Nutrition Examination Survey for 3590 participants aged 12 to 19 years from 1999 to 2014. SDOH variables were chosen and an SDOH score assigned (range, 0–7 points; higher=more favorable). CVH was classified according to American Heart Association criteria. We estimated population prevalence and used multivariable linear and polytomous logistic regression for associations between SDOH and CVH. SDOH varied by group, with the non‐Hispanic White group (n=1155) having a higher/better mean SDOH score compared with non‐Hispanic Black (n=1223) and Mexican American groups (n=1212). Associations between SDOH and CVH differed between racial and ethnic groups (interaction P P P =0.001; OR 1.1 [1.0–1.2] for moderate CVH; OR, 1.3 [1.1–1.6] for high CVH) and were not significant among the non‐Hispanic Black group (β, 0.07; P =0.464). Conclusions SDOH and CVH were more favorable for non‐Hispanic White adolescents compared with non‐Hispanic Black and Mexican American adolescents. SDOH were strongly associated with CVH among the non‐Hispanic White group. Racially and culturally sensitive public policy approaches may improve CVH in US adolescents.

Neurodevelopmental impairment is a common and important long-term morbidity among infants with congenital heart disease (CHD). More than half of those with complex CHD will demonstrate some form of neurodevelopmental, neurocognitive, and/or psychosocial dysfunction requiring specialized care and impacting long-term quality of life. Preventing brain injury and treating long-term neurologic sequelae in this high-risk clinical population is imperative for improving neurodevelopmental and psychosocial outcomes. Thus, cardiac neurodevelopmental care is now at the forefront of clinical and research efforts. Initial research primarily focused on neurocritical care and operative strategies to mitigate brain injury. As the field has evolved, investigations have shifted to understanding the prenatal, genetic, and environmental contributions to impaired neurodevelopment. This article summarizes the recent literature detailing the brain abnormalities affecting neurodevelopment in children with CHD, the impact of genetics on neurodevelopmental outcomes, and the best practices for neonatal neurocritical care, focusing on developmental care and parental support as new areas of importance. A framework is also provided for the infrastructure and resources needed to support CHD families across the continuum of care settings.

$\kappa$CrB is a ${\sim}2.5\,$Gyr old K1 sub-giant star, with an eccentric exo-Jupiter at ${\sim}2.8\,$au and a debris disc at tens of au. We present ALMA Band 6 ($1.3\,$mm) and HST scattered light ($0.6\,\mu$m) images, demonstrating $\kappa$CrB's broad debris disc, covering an extent $50{-}180\,$au in the millimetre (peaking at $110\,$au), and $51{-}280\,$au in scattered light (peaking at $73\,$au). By modelling the millimetre emission, we estimate the dust mass as ${\sim}0.016\,M{\oplus}$, and constrain lower-limit planetesimal sizes as $D_{\rm{max}}{>}1\,$km and the planetesimal belt mass as $M_{\rm{disc}}{>}1\,M_{\oplus}$. We constrain the properties of an outer body causing a linear trend in 17 years of radial velocity data to have a semi-major axis $8{-}66\,$au and a mass $(0.4{-}120)\,M_{\rm{Jup}}$. There is a large inner cavity seen in the millimetre emission, which we show is consistent with carving by such an outer massive companion with a string of lower mass planets. Our scattered light modelling shows that the dust must have a high anisotropic scattering factor ($g{\sim}0.8{-}0.9$) but an inclination ($i{\sim}30{-}40\,$degrees) that is inferred to be significantly lower than the $i{\sim}61\,$degrees millimetre inclination. The origin of such a discrepancy is unclear, but could be caused by a misalignment in the micron and millimetre sized dust. We place an upper limit on the CO gas mass of $M_{\rm{CO}}{, Comment: Accepted for publication in MNRAS. 21 pages, 14 figures

Hypothesis: We hypothesized that a single regimen of no or limited diuretics post-discharge after pediatric cardiac surgery for patients with two ventricles is not inferior to prolonged diuretics for prevention of readmission for pleural effusion. Material and Methods: A prospective, one-armed, safety non-inferiority trial with historical controls was performed at a single center, quaternary, children’s hospital. Inclusion criteria were children aged 3 months to 18 years after pediatric cardiac surgery resulting in a two- ventricle repair between 7/2020 and 7/2021. Eligible patients were compared with patients from a five-year historical period (selected using a database search). The intervention was that “regular risk” patients received no diuretics and pre-specified “high risk” patients received five days of twice per day furosemide at discharge. Results: 61 subjects received the intervention. None were readmitted for pleural effusions, though 1 subject was treated for a symptomatic pleural effusion with outpatient furosemide. The study was halted after an interim analysis demonstrated that 4 subjects were readmitted with pericardial effusion during the study period versus 2 during the historical control (2.9% versus 0.2%, p = 0.003). Conclusions: We found no evidence that limited post-discharge diuretics results in an increase in readmissions for pleural effusions. This conclusion is limited as not enough subjects were enrolled to definitively show that this strategy is not inferior to the historical practice. There was a small, but statistically significant, increase in readmissions for pericardial effusions after implementation of this study protocol.

A prospective, one-armed, safety non-inferiority trial with historical controls was performed at a single-center, quaternary, children's hospital. Inclusion criteria were children aged 3 months-18 years after pediatric cardiac surgery resulting in a two-ventricle repair between 7/2020 and 7/2021. Eligible patients were compared with patients from a 5-year historical period (selected using a database search). The intervention was that "regular risk" patients received no diuretics and pre-specified "high risk" patients received 5 days of twice per day furosemide at discharge. 61 Subjects received the intervention. None were readmitted for pleural effusions, though 1 subject was treated for a symptomatic pleural effusion with outpatient furosemide. The study was halted after an interim analysis demonstrated that 4 subjects were readmitted with pericardial effusion during the study period versus 2 during the historical control (2.9% versus 0.2%, P = 0.003). We found no evidence that limited post-discharge diuretics results in an increase in readmissions for pleural effusions. This conclusion is limited as not enough subjects were enrolled to definitively show that this strategy is not inferior to the historical practice. There was a statistically significant increase in readmissions for pericardial effusions after implementation of this study protocol which can lead to serious complications and requires further study before conclusions can be drawn regarding optimal diuretic regimens.

Truncus arteriosus is a congenital heart defect with high resource use, cost, and mortality. Value assessment (outcome relative to cost) can improve quality of care and decrease cost. This study hypothesized that truncus arteriosus repair at a high-volume center would result in better outcomes at lower cost (higher value) compared with a low-volume center.This study retrospectively analyzed a multicenter cohort of neonates undergoing truncus arteriosus repair (2004 to 2015) by using the Pediatric Health Information Systems database. Multivariate quantile, logistic, and negative binomial regression models were used to evaluate total hospital cost, in-hospital mortality, ventilation days, intensive care unit length of stay (LOS), hospital LOS, and days of inotropic agent use by center volume (high-volume3/year) and age at repair while adjusting for sex, ethnicity, race, genetic abnormality, prematurity, low birth weight, concurrent interrupted arch repair, and truncal valve repair.Of 1024 neonates with truncus arteriosus, 495 (48%) were treated at high-volume centers. Costs at the 75th percentile were lower at high-volume vs low-volume centers by $28,456 (P = .02) at all ages at repair. Patients at high-volume centers had lower median postoperative ventilation days (5 days vs 6 days; P.001), intensive care unit LOS (13 days vs 19 days; P.001), hospital LOS (23 days vs 28 days; P = .02), and inotropic agent use (3 days vs 4 days; P = .004). In-hospital mortality did not differ by center volume.In neonates undergoing truncus arteriosus repair, costs are lower and outcomes are better at high-volume centers, thus resulting in higher value at all ages of repair. Value-based interventions should be considered to improve outcomes and decrease cost in truncus arteriosus care.

The Neurodevelopmental and Psychological Outcomes Working Group of the Cardiac Neurodevelopmental Outcome Collaborative was formed in 2018 through support from an R13 grant from the National Heart, Lung, and Blood Institute with the goals of identifying knowledge gaps regarding the neurodevelopmental and psychological outcomes of individuals with CHD and investigations needed to advance science, policy, clinical care, and patient/family outcomes. Accurate characterisation of neurodevelopmental and psychological outcomes in children with CHD will drive improvements in patient and family outcomes through targeted intervention. Decades of research have produced a generalised perspective about neurodevelopmental and psychological outcomes in this heterogeneous population. Future investigations need to shift towards improving methods, measurement, and analyses of outcomes to better inform early identification, prevention, and intervention. Improved definition of underlying developmental, neuropsychological, and social-emotional constructs is needed, with an emphasis on symptom networks and dimensions. Identification of clinically meaningful outcomes that are most important to key stakeholders, including patients, families, schools and providers, is essential, specifically how and which neurodevelopmental differences across the developmental trajectory impact stakeholders. A better understanding of the discontinuity and patterns of neurodevelopment across the lifespan is critical as well, with some areas being more impactful at some ages than others. Finally, the field needs to account for the impact of race/ethnicity, socio-economic status, cultural and linguistic diversity on our measurement, interpretation of data, and approach to intervention and how to improve generalisability to the larger worldwide population of patients and families living with CHD.

In 2018, the Neurodevelopmental and Psychosocial Interventions Working Group of the Cardiac Neurodevelopmental Outcome Collaborative convened through support from an R13 grant from the National Heart, Lung, and Blood Institute to survey the state of neurodevelopmental and psychosocial intervention research in congenital heart disease and to propose a slate of critical questions and investigations required to improve outcomes for this growing population of survivors and their families. Prior research, although limited, suggests that individualized developmental care interventions delivered early in life are beneficial for improving a range of outcomes including feeding, motor and cognitive development, and physiological regulation. Interventions to address self-regulatory, cognitive, and social-emotional challenges have shown promise in other medical populations yet their applicability and effectiveness for use in individuals with congenital heart disease have not been examined. To move this field of research forward, we must strive to better understand the impact of neurodevelopmental and psychosocial intervention within the congenital heart disease population including adapting existing interventions for individuals with congenital heart disease. We must examine the ways in which dedicated cardiac neurodevelopmental follow-up programs bolster resilience and support children and families through the myriad transitions inherent to the experience of living with congenital heart disease. And we must ensure that interventions are person-/family-centered, inclusive of individuals from diverse cultural backgrounds as well as those with genetic/medical comorbidities, and proactive in their efforts to include individuals who are at highest risk but who may be traditionally less likely to participate in intervention trials.

To determine whether weight gain velocity (g/kg/day) 30 days after initiation of feeds following cardiac surgery and other clinical outcomes improve in infants with single ventricle physiology fed an exclusive human milk diet compared with a mixed human and bovine diet.In this multicenter, randomized, single blinded, controlled trial, term neonates ≤7 days of age with SVP and anticipated cardiac surgical palliation within 30 days of birth were enrolled at 10 US centers. Both groups received human milk if fed preoperatively. During the 30 days after feeds were started postoperatively, infants in the intervention group () received human milk fortified once enteral intake reached 60 mL/kg/day with a human milk-based fortifier designed for term neonates. The control group received standard fortification with formula once enteral intake reached 100 mL/kg/day. Perioperative feeding and parenteral nutrition study algorithms were followed.107 neonates were enrolled (EHM=55, control=52). Baseline demographics and characteristics were similar between groups. Median weight gain velocity at study completion was higher in EHM vs control group (25 [IQR, 11-43] vs 17 [2-26] g/day, respectively; p=0.008). Other growth measures were similar between groups. Necrotizing enterocolitis of all Bell stages was higher in the control group (15.4 % vs 3.6%, respectively, p=0.04). Incidence of other major morbidities, surgical complications, length of hospital stay, and hospital mortality were similar between groups.Neonates with SVP have improved short-term growth and decreased risk of NEC when receiving an exclusive human milk diet following stage 1 surgical palliation.

Background: Surgery is the mainstay of treatment for gastric volvulus. Despite its rarity, early experience from recent publications suggests that laparoscopy is a safe and effective approach for t...

We report the synthesis and structural characterization of a main-chain liquid crystal polymer constituted by a 1,2,4-oxadiazole-based bent-core repeat unit. For the first time, a liquid crystal polymer made of bent mesogenic units is demonstrated to exhibit cybotactic order in the nematic phase. Coupled with the chain-bond constraints, cybotaxis results in maximized molecular correlations that make this material of great potential in the search for the elusive biaxial and ferroelectric nematic phases. Indeed, repolarization current measurements in the nematic phase hint at a ferroelectric-like switching response (upon application of an electric field of only 1.0 V μm–1) that, albeit to be definitely confirmed by complementary techniques, is strongly supported by the comparative repolarization current measurements in the nematic and isotropic phases. Finally, the weak tendency of this polymer to crystallize makes it possible to supercool the cybotactic nematic phase down to room temperature, thus, paving ...

OBJECTIVES We leveraged decomposition analysis, commonly used in labor economics, to understand determinants of cost differences related to location of admission in children undergoing neonatal congenital heart surgery. DESIGN A retrospective cohort study. SETTING Pediatric Health Information Systems database. PATIENTS Neonates (

The Fontan Outcomes Network was created to improve outcomes for children and adults with single ventricle CHD living with Fontan circulation. The network mission is to optimise longevity and quality of life by improving physical health, neurodevelopmental outcomes, resilience, and emotional health for these individuals and their families. This manuscript describes the systematic design of this new learning health network, including the initial steps in development of a national, lifespan registry, and pilot testing of data collection forms at 10 congenital heart centres.

Drawing on a wealth of archaeological evidence, this chapter seeks to explore the development of urban expansion and civic pride through the emergence of differing designs of swimming pools. These iconic buildings are placed in their historical context and comparisons are drawn with contemporary developments in other fields of architecture. The key motivational factors of hygiene, politics, and recreation are analyzed, as is the emergence of civic pride. Both functionality and status of the new building types are explored, as the communities evolved into the modern world. The chapter further demonstrates how buildings and architectural design are not solely functional, but also reflect emerging elements of status, social and political power dynamics.