Duct-dependent pulmonary circulation has traditionally been addressed by the Blalock-Taussig-Thomas shunts (BTTS). Recently, catheter-based alternatives such as ductal stenting have emerged as a particularly advantageous option, especially in resource-constrained settings. This article delves into the nuances of ductal stenting within low-resource environments, highlighting its relative ease of application, reduced morbidity, and cost-effectiveness as key factors in its favor. Comparisons in mortality between the two procedures are however likely to be confounded by selection biases. Ductal stenting appears to be particularly beneficial for palliating older infants and children with cyanotic congenital heart disease and diminished pulmonary blood flow who present late. Additionally, it serves as a valuable tool for left ventricular training in late-presenting transposition with an intact ventricular septum. A meticulous pre-procedure echocardiographic assessment of anatomy plays a pivotal role in planning access and hardware, with additional imaging seldom required for this purpose. The adaptation of adult coronary hardware has significantly enhanced the technical feasibility of ductal stenting. However, challenges such as low birth weight and sepsis specifically impact the performance of ductal stenting and patient recovery in low-resource environments. There is potential for systematic application of quality improvement processes to optimize immediate and long-term outcomes of ductal stenting. There is also a need to prospectively examine the application of ductal stenting in low-resource environments through multi-center registries.
In recent issues of the Journal of the Society for Cardiovascular Angiography and Interventions and the Journal of the American College of Cardiology: Cardiovascular Interventions, Holzer and colleagues presented an Expert Consensus Document titled: "PICS / AEPC / APPCS / CSANZ / SCAI / SOLACI: Expert consensus statement on cardiac catheterization for pediatric patients and adults with congenital heart disease." This Expert Consensus Document is a massively important contribution to the community of paediatric and congenital cardiac care. This document was developed as an Expert Consensus Document by the Pediatric and Congenital Interventional Cardiovascular Society, the Association for European Paediatric and Congenital Cardiology, the Asia-Pacific Pediatric Cardiac Society, the Cardiac Society of Australia and New Zealand, the Society for Cardiovascular Angiography and Interventions, and the Latin American Society of Interventional Cardiology, as well as the Congenital Cardiac Anesthesia Society and the American Association of Physicists in Medicine.As perfectly stated in the Preamble of this Expert Consensus Document, "This expert consensus document is intended to inform practitioners, payors, hospital administrators and other parties as to the opinion of the aforementioned societies about best practices for cardiac catheterisation and transcatheter management of paediatric and adult patients with congenital heart disease, with added accommodations for resource-limited environments." And, the fact that the authorship of this Expert Consensus Document includes global representation is notable, commendable, and important.This Expert Consensus Document has the potential to fill an important gap for this patient population. National guideline documents for specific aspects of interventions in patients with paediatric heart disease, including training guidelines, do exist. However, this current Expert Consensus Document authored by Holzer and colleagues provides truly globally applicable standards on cardiac catheterisation for both paediatric patients and adults with congenital heart disease (CHD).Our current Editorial provides different regional perspectives from senior physicians dedicated to paediatric and congenital cardiac care who are practicing in Europe, the Asia-Pacific region, Latin America, Australia/New Zealand, and North America. Establishing worldwide standards for cardiac catheterisation laboratories for children and adults with CHD is a significant stride towards improving the quality and consistency of care. These standards should not only reflect the current state of medical knowledge but should also be adaptable to future advancements, ultimately fostering better outcomes and enhancing the lives of individuals affected by CHD worldwide.Ensuring that these standards are accessible and adaptable across different healthcare settings globally is a critical step. Given the variability in resources and infrastructure globally, the need exists for flexibility and tailoring to implement recommendations.The potential impact of the Expert Consensus Document and its recommendations is likely significant, but heterogeneity of healthcare systems will pose continuing challenges on healthcare professionals. Indeed, this heterogeneity of healthcare systems will challenge healthcare professionals to finally close the gap between acceptable and ideal in the catheterisation of patients with paediatric and/or congenital heart disease.
Somewhat pitch-forked into a role it had been envisioning for itself for a long time now by the rapidly changing politico-administrative dynamics of the nations across the world and emerging and re-emerging crises limited not the least to wars and pandemics, India needs to leverage its strengths to deliver on the promise it has long held. But India's struggle to stem the outward flow of many of the brightest may just be one among the many factors that can play a spoilsport. The civilizational strength of India has been its cultural-scientific epistemology, strengthening the exploration of which will help it position itself as the global leader. The freedom to question and seek answers, no matter how successful a hypothesis has been in the past, is consistent with its (India's) epistemology, both scientific and cultural.
Aluminum metal cast composites (AMCCs) are frequently used in high-tech sectors such as automobiles, aerospace, biomedical, electronics, and others to fabricate precise and especially responsible parts. The mechanical and wear behavior of the metal matrix composites (MMCs) is anticipated to be influenced by the cooling agent's action and the cooling temperature. This research paper presents the findings of a series of tests to investigate the mechanical, wear, and fracture behavior of hybrid MMCs made of Al7075 reinforced by varying wt % of nano-sized Al2O3 and Gr and quenched with water and ice cubes. The heat-treated Al7075 alloy hybrid composites were evaluated for their hardness, tensile, and wear behavior, showcasing a significant process innovation. The heat treatment process greatly improved the hybrid composites' mechanical and wear performance. The samples quenched in ice attained the highest hardness of 119 VHN. There is a 45.37% improvement in the hardness of base alloy with the addition of 3% of Al2O3 and 1% of graphite particles. Further, the highest tensile and compression strengths were found in the ice-quenched 3% Al2O3 and 1% graphite hybrid composites with improvements of 34.2 and 48.83%, respectively, compared to the water-quenched base alloy. Under the samples quenched in ice, the mechanical and wear behavior improved. The tensile fractured surface showed voids, particle pullouts, and dimples. The worn-out surface of wear test samples of the created hybrid composite had micro pits, delamination layers, and microcracks.
Non-clustered protocadherins (ncPcdhs) are adhesive molecules with spatio-temporally regulated overlapping expression in the developing nervous system. Although their unique role in neurogenesis has been widely studied, their combinatorial role in brain physiology and pathology is poorly understood. Using probabilistic cell typing by in situ sequencing, we demonstrate combinatorial inter- and intra-familial expression of ncPcdhs in the developing mouse cortex and hippocampus, at single-cell resolution. We discovered the combinatorial expression of Protocadherin-19 (Pcdh19), a protein involved in PCDH19-clustering epilepsy, with Pcdh1, Pcdh9 or Cadherin 13 (Cdh13) in excitatory neurons. Using aggregation assays, we demonstrate a code-specific adhesion function of PCDH19; mosaic PCDH19 absence in PCDH19+9 and PCDH19 + CDH13, but not in PCDH19+1 codes, alters cell-cell interaction. Interestingly, we found that PCDH19 as a dominant protein in two heterophilic adhesion codes could promote trans-interaction between them. In addition, we discovered increased CDH13-mediated cell adhesion in the presence of PCDH19, suggesting a potential role of PCDH19 as an adhesion mediator of CDH13. Finally, we demonstrated novel cis-interactions between PCDH19 and PCDH1, PCDH9 and CDH13. These observations suggest that there is a unique combinatorial code with a cell- and region-specific characteristic where a single molecule defines the heterophilic cell-cell adhesion properties of each code.
Brain , Cell Adhesion , Protocadherins , Animals , Mice , Brain/cytology , Brain/growth & development , Epilepsy/metabolism , Neurons/metabolism
Heart University [https://www.heartuniversity.org/] is a free educational website providing structured training curricula with knowledge-based testing and access to webinars and conference recordings for practicing and in-training providers of paediatric and congenital cardiac care. To date, there are over 15,000 registered website users from over 140 countries on Heart University, with over 2,000 training modules and/or recorded educational videos. Heart University has developed an "asynchronous" educational lecture series entitled "Pediatric and Congenital Cardiac Care in Resource-Limited Settings." This recorded lecture series is specifically focused on topics relevant to practicing paediatric and/or congenital cardiac care in low-resource settings.A relatively new initiative, "Cardiology Across Continents," supplements the existing educational resources for providers of paediatric and/or congenital cardiac care in low-income countries and lower-middle-income countries by providing an additional live, interactive, case-based forum. Sessions occur every 1-2 months and focus on challenging cases from diagnostic or management perspective with a view to promote collaboration between partnered institutions. "Cardiology Across Continents" is an expanding initiative that facilitates learning and collaboration between clinicians across varied practice settings via interactive case discussions. We welcome trainees and providers of paediatric and congenital cardiac care to join the sessions and invite any insight that can enhance learning for clinicians around the world. This manuscript describes "Cardiology Across Continents" and discusses the development, history, current status, and future plans of Heart University.
Family medicine is the academic discipline, knowledge domain and specialty of family physicians or family doctors globally. Family medicine is rapidly developing in India amidst resistance and criticism. Many opponents identify family medicine as a western concept and argue for its non suitability for implementation in India. Family medicine or family physician is not a new concept for the Indian people. The family doctor concept originated in India from the community-based Vaidya system - an ancient old tradition of the Indian civilisation. A 'Vaidya' typically refers to a local physician engaging with the population. The Vaidya used to provide personalised care and primary medical care to individuals and families. The Vaidya remained the 'Family Physician', and this identity and profession has an unbreeched association of more than several millennia with the Indian population. It is to be noted that all the goals of Bachelor of Medicine and Bachelor of Surgery (MBBS) training in India, the aspirations, skills and competencies for trainees, as defined by the National Medical Commission (NMC), can be identified as the academic discipline and vocation of family physicians. However, family medicine has not yet been included as a distinct and mandatory subject for MBBS students by the NMC. The demand for personalised health care within the community by the family doctors has never diminished but has only been artificially restricted. Family physicians contribute significantly to the promotion of health, prevention of diseases and the management of various health conditions in the Indian context. We look forward to the integration of family physician and family doctor concepts within the mainstream medical education system. It is expected that family medicine will become part of MBBS curriculum as promulgated in the NMC Act 2019.
Transcatheter closure of perimembranous ventricular septal defect (PmVSD) is an established procedure. However, the occurrence of complete heart block limits its scope. The newer KONAR-MF™ occluder has specific design characteristics that may improve the safety of PmVSD closure. The objective of the study was to describe the efficacy and mid-term follow-up of transcatheter closure of PmVSD using KONAR-MF™. The study was conducted prospectively in 3 Indian centers (January 2018-December 2022). PmVSD closure was done by both antegrade and retrograde methods, and patients were followed up at 1, 3, 6, 12 months, and annually after that. 121 out of 123 patients were included with the following characteristics: median age 4.4 (0.18-40) years; weight 15 (2.1-88) kg; mean Qp/Qs ratio 1.87 ± 0.52 and pulmonary artery mean pressure: 22 ± 6.9 mmHg. The procedure was successful in all but 3; the device was removed due to significant residual shunt (n = 2) and new development of aortic regurgitation (AR) (≥ mild) in 1. The median defect size was 5.2 (2.5-12) mm. Device sizes from 6/4 to 14/12 were deployed (median fluoroscopy time 13.3 min; range 3.6-47.8). Shunt occlusion rates were 90%-Immediate, 95%-pre-discharge, and 97%-1 month, with no instances of complete heart block after the procedure and during follow-up. Six had new onset AR (mild: 2, trivial 4), and one had increased tricuspid regurgitation. All patients were well during follow-up (median: 20 months; range: 6-46). The new KONAR-MF™ occluder appears to be a promising and safe alternative for the closure of the PmVSD; further long-term follow is merited.
Graphene's two-dimensional structural arrangement has sparked a revolutionary transformation in the domain of conductive transparent devices, presenting a unique opportunity in the renewable energy sector. This comprehensive Review critically evaluates the most recent advances in graphene production and its employment in solar cells, focusing on dye-sensitized, organic, and perovskite devices for bulk heterojunction (BHJ) designs. This comprehensive investigation discovered the following captivating results: graphene integration resulted in a notable 20.3% improvement in energy conversion rates in graphene-perovskite photovoltaic cells. In comparison, BHJ cells saw a laudable 10% boost. Notably, graphene's 2D internal architecture emerges as a protector for photovoltaic devices, guaranteeing long-term stability against various environmental challenges. It acts as a transportation facilitator and charge extractor to the electrodes in photovoltaic cells. Additionally, this Review investigates current research highlighting the role of graphene derivatives and their products in solar PV systems, illuminating the way forward. The study elaborates on the complexities, challenges, and promising prospects underlying the use of graphene, revealing its reflective implications for the future of solar photovoltaic applications.
Fins are widely used in many industrial applications, including heat exchangers. They benefit from a relatively economical design cost, are lightweight, and are quite miniature. Thus, this study investigates the influence of a wavy fin structure subjected to convective effects with internal heat generation. The thermal distribution, considered a steady condition in one dimension, is described by a unique implementation of a physics-informed neural network (PINN) as part of machine-learning intelligent strategies for analyzing heat transfer in a convective wavy fin. This novel research explores the use of PINNs to examine the effect of the nonlinearity of temperature equation and boundary conditions by altering the hyperparameters of the architecture. The non-linear ordinary differential equation (ODE) involved with heat transfer is reduced into a dimensionless form utilizing the non-dimensional variables to simplify the problem. Furthermore, Runge-Kutta Fehlberg's fourth-fifth order (RKF-45) approach is implemented to evaluate the simplified equations numerically. To predict the wavy fin's heat transfer properties, an advanced neural network model is created without using a traditional data-driven approach, the ability to solve ODEs explicitly by incorporating a mean squared error-based loss function. The obtained results divulge that an increase in the thermal conductivity variable upsurges the thermal distribution. In contrast, a decrease in temperature profile is caused due to the augmentation in the convective-conductive variable values.
The National Medical Commission (NMC) of India has issued new guideline for post graduate medical courses in India on 15th January 2024. These Guidelines may be called the "Minimum Standard of Requirements for Postgraduate Courses-2023 (PGMSR-2023)". These guidelines will come into force with immediate effect. Unfortunately, Family Medicine specialty has been entirely excluded from this document, despite clear mandate in the National Medical Commission Act 2019. Previously, the Undergraduate Medical Education Board of NMC did not include the Family Medicine as a mandatory department for training at MBBC Course. In the absence of a specific policy on medical education, a careful planning is required for number of post graduate residency positions across India depending upon population coverage and morbidity patterns. So, far during past three decades the increase in the number of post graduate residency posts/ seats have been random. There has been no clear-cut policy by the government or by the regulator itself. There appears to be no mapping for specialty need across geographical territories and population density in the background of the morbidity pattern. Under section 24(1)(c) of the National Medical Commission Act 2019 The Under-Graduate Medical Education Board shall perform the following functions, namely: - (c) develop competency-based dynamic curriculum for addressing the needs of primary health services, community medicine and family medicine to ensure healthcare in such areas, in accordance with the provisions of the regulations made under this Act; Under section 25. (1)(j) National Medical Commission Act 2019 The Post-Graduate Medical Education Board shall perform the following functions, namely: - (j) promote and facilitate postgraduate courses in family medicine. Under section 57. (1) The Commission may, after previous publication, by notification, make regulations consistent with this Act and the rules made thereunder to carry out the provisions of this Act. (2), and without prejudice to the generality of the preceding power, (p) the curriculum for primary medicine, community medicine, and family medicine under clause (c) of sub-section (1) of section 24. It is to be noted that Family Medicine is a community-based clinical discipline, all parameters for the graduate Family Medicine department, training, and faculty eligibility have been kept as per other hospitalist disciplines. It is the mandate of the Post Graduate Board of NMC to promote the PG program in Family Medicine. Suggestions articulated in this paper may be worthy of consideration of the esteemed members of National Medical Commission.
Political will is the key to public health policy-making and a major driving force for the attainment of Universal Health Coverage (UHC) in any nation. To achieve UHC, the Indian government laid down National Health Policy in 1983 and updated it in 2002 and recently in 2017. This recent policy emphasized increasing healthcare spending and economic growth. In the current budget, there is an increment in the share of GDP of 0.34% from the previous year's allocation, but still staggering for the envisaged 2.5% to achieve UHC. Enthusiastic announcements of opening 157 new nursing colleges, a separate programme for eliminating sickle cell anemia by 2047, and Centers of excellence establishment for pharma companies for promoting research and development and focusing on Particularly Vulnerable Tribal Groups (PVTGs) are the few overarching and new highlights in the current budget. But, in a country so huge and varied in terms of its needs in every sector, the announcements in the financial budget speech taking India forward in becoming a "shining star" is a matter of debate. This is an attempt to review the budget for this financial year in the healthcare sector and what it means: is the country willing to build a self-driven healthcare sector in the Amrit Kaal with strong public finances and a robust financial sector through "efforts by all"?
Clustering Epilepsy (CE) is a neurological disorder caused by pathogenic variants of the Protocadherin 19 (PCDH19) gene. PCDH19 encodes a protein involved in cell adhesion and Estrogen Receptor α mediated-gene regulation. To gain further insights into the molecular role of PCDH19 in the brain, we investigated the PCDH19 interactome in the developing mouse hippocampus and cortex. Combined with a meta-analysis of all reported PCDH19 interacting proteins, our results show that PCDH19 interacts with proteins involved in actin, microtubule, and gene regulation. We report CAPZA1, αN-catenin and, importantly, ß-catenin as novel PCDH19 interacting proteins. Furthermore, we show that PCDH19 is a regulator of ß-catenin transcriptional activity, and that this pathway is disrupted in CE individuals. Overall, our results support the involvement of PCDH19 in the cytoskeletal network and point to signalling pathways where PCDH19 plays critical roles.
Environmental contamination is aninsistent concern affecting human health and the ecosystem. Wastewater, containing heavy metals from industrial activities, significantly contributes to escalating water pollution. These metals can bioaccumulate in food chains, posing health risks even at low concentrations. Copper (Cu), an essential micronutrient, becomes toxic at high levels. Activities like mining and fungicide use have led to Copper contamination in soil, water, and sediment beyond safe levels. Copper widely used in industries, demands restraint of heavy metal ion release into wastewater for ecosystem ultrafiltration, membrane filtration, nanofiltration, and reverse osmosis, combat heavy metal pollution, with emphasis on copper.Physical and chemical approaches are efficient, large-scale feasibility may have drawbackssuch as they are costly, result in the production of sludge. In contrast, bioremediation, microbial intervention offers eco-friendly solutions for copper-contaminated soil. Bacteria and fungi facilitate these bioremediation avenues as cost-effective alternatives. This review article emphasizes on physical, chemical, and biological methods for removal of copper from the wastewater as well asdetailing microorganism's mechanisms to mobilize or immobilize copper in wastewater and soil.
Environmental Restoration and Remediation , Metals, Heavy , Soil Pollutants , Humans , Copper/analysis , Ecosystem , Wastewater , Soil Pollutants/analysis , Metals, Heavy/toxicity , Soil , Biodegradation, Environmental
BACKGROUND: Developmental delays in children are assessed in four basic domains: gross motor, fine motor, social, and language. Early years of life are crucial in a child's development, so it is imperative that parents be aware of developmental milestones to facilitate early diagnosis and treatment in case of a developmental delay. This study assessed parental knowledge, attitude, and practices regarding children's developmental milestones and associated "red flags". METHODS: A cross-sectional study was conducted at the Department of Pediatrics at Liaquat National Hospital, Karachi. 390 parents, who had at least one child under 5 years of age, with no diagnosed developmental delay, were interviewed during outpatient clinic visits. The questionnaire consisted of three components to assess parental knowledge, attitude, and practices. RESULTS: 59% and 54% of parents had poor knowledge of gross and fine motor milestones respectively; In the social domain, 56% of the respondents had inadequate knowledge. 42% had inadequate knowledge of language milestones; 29% of parents strongly agreed that their pediatricians provide satisfactory information regarding red flags of developmental milestones. 60% of parents strongly agreed that their child's developmental delay would be a cause of concern for them. In the case of developmental delay, 55% of parents said they would consult a general pediatrician, 11% preferred a pediatric neurologist, 21% opted for a developmental pediatrician and 13% opted for a family physician. Residence and family systems were found to be associated with language-related milestones with significantly higher odds of knowledge among urban residents than rural ones and a significantly lower likelihood of language milestones knowledge among joint families than nuclear families. Female gender was found to be significantly associated with positive attitude. CONCLUSION: The majority of our respondents showed considerably poor knowledge regarding developmental milestones. This highlights the need to devise ways to educate parents on this subject to enable them to vigilantly monitor their child's developmental status and any associated abnormalities and ultimately facilitate the right course of action.
Child Development , Health Knowledge, Attitudes, Practice , Child , Female , Humans , Cross-Sectional Studies , Pakistan , Parents , Infant , Child, Preschool
We implicated the X-chromosome THOC2 gene, which encodes the largest subunit of the highly-conserved TREX (Transcription-Export) complex, in a clinically complex neurodevelopmental disorder with intellectual disability as the core phenotype. To study the molecular pathology of this essential eukaryotic gene, we generated a mouse model based on a hypomorphic Thoc2 exon 37-38 deletion variant of a patient with ID, speech delay, hypotonia, and microcephaly. The Thoc2 exon 37-38 deletion male (Thoc2Δ/Y) mice recapitulate the core phenotypes of THOC2 syndrome including smaller size and weight, and significant deficits in spatial learning, working memory and sensorimotor functions. The Thoc2Δ/Y mouse brain development is significantly impacted by compromised THOC2/TREX function resulting in R-loop accumulation, DNA damage and consequent cell death. Overall, we suggest that perturbed R-loop homeostasis, in stem cells and/or differentiated cells in mice and the patient, and DNA damage-associated functional alterations are at the root of THOC2 syndrome.
Intellectual Disability , Transcription Factors , Humans , Male , Mice , Animals , Transcription Factors/metabolism , R-Loop Structures , Active Transport, Cell Nucleus , Intellectual Disability/genetics , DNA Damage , Phenotype , RNA, Messenger/metabolism
Recent studies focus on enhancing the mechanical features of natural fiber composites to replace synthetic fibers that are highly useful in the building, automotive, and packing industries. The novelty of the work is that the woven areca sheath fiber (ASF) with different fiber fraction epoxy composites has been fabricated and tested for its tribological responses on three-body abrasion wear testing machines along with its mechanical features. The impact of the fiber fraction on various features is examined. The study also revolves around the development and validation of a machine learning predictive model using the random forest (RF) algorithm, aimed at forecasting two critical performance parameters: the specific wear rate (SWR) and the coefficient of friction (COF). The void fraction is observed to vary between 0.261 and 3.8% as the fiber fraction is incremented. The hardness of the mat rises progressively from 40.23 to 84.26 HRB. A fair ascent in the tensile strength and its modulus is also observed. Even though a short descent in flexural strength and its modulus is seen for 0 to 12 wt % composite specimens, they incrementally raised to the finest values of 52.84 and 2860 MPa, respectively, pertinent to the 48 wt % fiber-loaded specimen. A progressive rise in the ILSS and impact strength is perceptible. The wear behavior of the specimens is reported. The worn surface morphology is studied to understand the interface of the ASF with the epoxy matrix. The RF model exhibited outstanding predictive prowess, as evidenced by high R-squared values coupled with low mean-square error and mean absolute error metrics. Rigorous statistical validation employing paired t tests confirmed the model's suitability, revealing no significant disparities between predicted and actual values for both the SWR and COF.
Background: Rheumatic fever and rheumatic heart disease is endemic in India. Mitral valve replacement with mechanical valve is the commonest surgical procedure performed in rheumatic heart disease (RHD). However, there are no studies reporting the long-term outcomes of mechanical mitral valve replacement in rheumatic heart disease from India. Objective: The primary objective of the study was to look at the long-term survival following mechanical mitral valve replacement in RHD. The secondary objectives included follow up complications and event-free survival. Methods: For this study, 238 patients who underwent mitral valve replacement with TTK Chitra™ valve from 1st January 2006 to 31st December 2018 for RHD were included for analysis and reporting. The median follow-up period was 3371.50 days (9.3 years). Total follow-up was 2044 patient-years. Results: The mean age of the study population was 39.72 ± 10.48 years (range: 18-68 years). Out of 238 patients operated, 155 patients (65.12%) were alive and 69 patients (28.99%) were dead, and 14 patients (5.88%) were lost to follow-up. The operative mortality was 6 (2.52%) and the follow-up mortality was 63 (26.47%). The reasons for follow-up mortality were cardiac complications in 22 (34.9%) patients, valve-related complications in 18 (28.5%) patients, sudden unexplained death in 13 (20.6%) patients, and non-valve/ non-cardiac death in 10patients (15.8%). The one-year survival was 94.0%, five-year survival was 83.6%, ten-year survival was 70.6% and 15-year survival was 62.9%. During follow-up, valve-related events occurred in 123(52%) patients. The 15-year event-free survival was 33.0%. Conclusions: The long term outcome of mechanical valve replacement of the mitral valve in RHD patients was less than favorable. Both cardiac complications and mechanical valve related complications reduced their survival.
