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Journal articles on the topic 'Healthy equity'
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1
Smith, Kenneth D. "From Healthy Homes to Health Equity." Journal of Public Health Management and Practice 16 (2010): S3—S4. http://dx.doi.org/10.1097/phh.0b013e3181ee0aaa.
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Venkatapuram, Sridhar, Hans-Jörg Ehni, and Abha Saxena. "Equity and healthy ageing." Bulletin of the World Health Organization 95, no. 11 (September 18, 2017): 791–92. http://dx.doi.org/10.2471/blt.16.187609.
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Spiegel, Jerry M., and Jaime Breilh. "Advancing health equity in healthy cities: Framing matters." Journal of Public Health Policy 38, no. 2 (February 27, 2017): 234–39. http://dx.doi.org/10.1057/s41271-017-0070-3.
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TSOUROS, AGIS D. "Equity and the Healthy Cities project." Health Promotion International 4, no. 2 (1989): 73–75. http://dx.doi.org/10.1093/heapro/4.2.73.
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Frankish, C. James, Brenda Kwan, Diane Gray, Andrea Simpson, and Nina Jetha. "Status report - Identifying equity-focussed interventions to promote healthy weights." Health Promotion and Chronic Disease Prevention in Canada 37, no. 3 (March 2017): 94–101. http://dx.doi.org/10.24095/hpcdp.37.3.05.
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Introduction We developed screening criteria to identify population health interventions with an equity focus for inclusion on the Public Health Agency of Canada’s Canadian Best Practices Portal. We applied them to the area of “healthy weights,” specifically, obesity prevention. Methods We conducted a review of the literature and obtained input from expert external reviewers on changes to midstream environments. Interventions had to identify outcomes for groups with an underlying social disadvantage. We included papers with a focus on equity and vulnerable populations, intervention and/or evaluation studies, social determinants of health and healthy weights or obesity prevention. We then appraised the shortlisted studies for quality of evidence to determine eligibility for inclusion as promising practices on the Canadian Best Practices Portal. Results Few of the references reviewed passed the equity screening criteria (26 out of 2823 published papers reviewed, or 0.9%). Six (of the 26) interventions qualified as promising practices. Conclusion The ability of the equity screening criteria to distinguish midstream-level interventions for obesity prevention suggests that the criteria have potential to be applied to other public health topics. What is most important about our work is that the Portal, which is no longer being updated but is still accessible, was broadened to include interventions with a focus on equity.
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Levine, Rachel L. "Healthy People 2030: A Beacon for Addressing Health Disparities and Health Equity." Journal of Public Health Management and Practice 27, no. 6 (November 2021): S220—S221. http://dx.doi.org/10.1097/phh.0000000000001409.
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Banham, David, John Lynch, and Jon Karnon. "An equity - effectiveness framework linking health programs and healthy life expectancy." Australian Journal of Primary Health 17, no. 4 (2011): 309. http://dx.doi.org/10.1071/py11034.
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South Australia’s Strategic Plan includes a target to improve the population’s healthy life expectancy. A common question among health policy and service planners is: ‘How do health programs and services in the community relate to healthy life expectancy?’ In response, this paper outlines an effectiveness and equity framework (EEF) for evaluating health interventions in applied settings. Using the example of coronary heart disease (CHD) management in general practice in South Australia, the EEF: (1) applies an internally consistent approach to accounting for population healthy life expectancy at state and smaller geographic levels; (2) estimates average population health gains from health programs, and gains across different socioeconomic subgroups within the community; (3) conducts economic evaluation by equating health gains against health system costs in population subgroups; (4) summarises relevant information about candidate intervention programs within a multi-criteria performance matrix for presentation to decision makers; (5) reassesses outcomes (and processes) following the implementation of a program and iteratively adds to the relevant knowledge and evidence base. The EEF offers a practical approach to selecting and evaluating intervention programs. The challenge is to develop system culture and data capture methods clearly focussed on linking health system activities to population health outcomes.
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Buregeya, Jean Marie, Christine Loignon, and Astrid Brousselle. "Contribution to healthy places: Risks of equity free health impact assessment." Evaluation and Program Planning 73 (April 2019): 138–45. http://dx.doi.org/10.1016/j.evalprogplan.2018.12.007.
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Mouton, Morgan, Ariel Ducey, Judith Green, Lorian Hardcastle, Steven Hoffman, Myles Leslie, and Melanie Rock. "Towards ‘smart cities’ as ‘healthy cities’: health equity in a digital age." Canadian Journal of Public Health 110, no. 3 (January 30, 2019): 331–34. http://dx.doi.org/10.17269/s41997-019-00177-5.
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Diczfalusy, Egon. "In search of human dignity: gender equity, reproductive health and healthy aging." International Journal of Gynecology & Obstetrics 59, no. 3 (December 1997): 195–206. http://dx.doi.org/10.1016/s0020-7292(97)00230-0.
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Kim, Jinhee. "Implications of the COVID-19 pandemic on health equity and healthy cities." Korean Journal of Health Education and Promotion 37, no. 4 (October 1, 2020): 81–89. http://dx.doi.org/10.14367/kjhep.2020.37.4.81.
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Yulinartati, Yulinartati. "ANALISIS KINERJA KEUANGAN SEBAGAI ALAT PREDIKSI KEBANGKRUTAN DENGAN MODEL DISKRIMINAN." JURNAL AKUNTANSI UNIVERSITAS JEMBER 10, no. 2 (March 31, 2015): 97. http://dx.doi.org/10.19184/jauj.v10i2.1253.
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The purpose of this study was to determine whether the Current Ratio (CR), Debt Equity Ratio (DER), Total Assets Over Turen (TATO), net profit margin (NPM), Debt to Assets Ratio (DAR), Return on Assets (ROA) , Return on Equity (ROE), Gross Profit Margin (GPM), Operating Profit Margin (OPM) influential in distinguishing healthy firms and perusahaa bankruptcy discriminant model. Based on discriminant analysis of known groups of healthy companies and a group of companies that went bankrupt differ significantly, from 9 (nine) variables are in use only 4 (four) variable Current Ratio, Debt Equity Ratio, Net Profit Margin, and Gross Profit Margin is selected and able to differentiate healthy companies and companies go bankrupt, while the 5 (five) of the variables, Turn Over Total Assets, Debt to Assets Ratio, Return on Assets, Return on Assets, and Operating Profit Margin are not able to differentiate healthy and bankrupt companies.
Keywords: Current Ratio ,Debt Equity Ratio, Total Assets Turen Over , Net profit Margin , Return on Assets, Return on Equity
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Lehne, Gesa, Claudia Voelcker-Rehage, Jochen Meyer, Karin Bammann, Dirk Gansefort, Tanja Brüchert, and Gabriele Bolte. "Equity Impact Assessment of Interventions to Promote Physical Activity among Older Adults: A Logic Model Framework." International Journal of Environmental Research and Public Health 16, no. 3 (February 1, 2019): 420. http://dx.doi.org/10.3390/ijerph16030420.
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Reducing social inequalities in health and health determinants, including physical activity (PA), is a major challenge for public health. PA-promoting interventions are increasingly implemented. Little is known, however, about the impact of these interventions on social inequalities. For prioritizing interventions most likely to be effective in reducing inequalities, studies of PA interventions need to conduct equity impact assessments. The aim of this article is to describe the development of a logic model framework for equity impact assessments of interventions to promote PA. The framework was developed within the prevention research network AEQUIPA—Physical activity and health equity: primary prevention for healthy ageing, informed by an equity-focused systematic review, expert interviews, exploratory literature searches, and joint discussions within the network. The framework comprises a general equity-focused logic model to be adapted to specific interventions. The intervention-specific equity-focused logic models illustrate the key elements relevant for assessing social inequalities in study participation, compliance with and acceptance of interventions, as well as the efficacy of interventions. Future work within AEQUIPA will reveal which key elements are most critical for the interventions’ equity impacts. Equity impact assessments are beneficial for prioritizing interventions most likely to be effective in reducing health inequalities.
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Sassi, Franco, Annalisa Belloni, Andrew J. Mirelman, Marc Suhrcke, Alastair Thomas, Nisreen Salti, Sukumar Vellakkal, Chonlathan Visaruthvong, Barry M. Popkin, and Rachel Nugent. "Equity impacts of price policies to promote healthy behaviours." Lancet 391, no. 10134 (May 2018): 2059–70. http://dx.doi.org/10.1016/s0140-6736(18)30531-2.
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Janzen, Cora, Michael Schwandt, and Josh Marko. "Embedding Health Equity Strategically within Healthy Built Environments to Improve Walkability ( breakout presentation )." Journal of Transport & Health 7 (December 2017): S43—S44. http://dx.doi.org/10.1016/j.jth.2017.11.072.
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Perrin, James M., Michael C. Lu, Amy Geller, and Jennifer E. DeVoe. "Vibrant and Healthy Kids: Aligning Science, Practice, and Policy to Advance Health Equity." Academic Pediatrics 20, no. 2 (March 2020): 160–62. http://dx.doi.org/10.1016/j.acap.2019.11.019.
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Hassell, Trevor A., Maisha T. Hutton, and D. Beverley Barnett. "Civil society promoting government accountability for health equity in the Caribbean: The Healthy Caribbean Coalition." Revista Panamericana de Salud Pública 44 (October 15, 2020): 1. http://dx.doi.org/10.26633/rpsp.2020.79.
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Achieving health equity and addressing the social determinants of health are critical to attaining the health and health-related targets of the 2030 Agenda for Sustainable Development and its Sustainable Development Goals. Frameworks for health, including the Sustainable Health Agenda for the Americas 2018 – 2030, emphasize reduction of health inequities and “leaving no one behind” in national sustainable development. Health equity includes advancing universal health and the primary health care approach, with equitable access for all people to timely, quality, comprehensive, people- and community-centered services that do not cause impoverishment. Equally important, and a hallmark of good governance, is accountability for such advances. Governments have primary responsibility for reducing health inequities and must be held accountable for their policies and performance. Civil society has been recognized as a key partner in advancing sustainable and equitable national development. Effective accountability mechanisms should include civic engagement. The Healthy Caribbean Coalition (HCC), the only Caribbean regional alliance of civil society organizations working to prevent and control noncommunicable diseases—a major health priority fueled by inequities—has played a significant role in holding governments accountable for advancing health equity. This case study examines factors contributing to the success of the HCC, highlighting work under its five strategic pillars—accountability, advocacy, capacity development, communication, and sustainability—as well as challenges, lessons learned, and considerations for greater effectiveness.
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Oppong, Peter Kwasi. "Influence of Brand Credibility, Satisfaction and Quality on Brand Equity in Non-Conventional Health Industry." Journal of Education and Vocational Research 11, no. 2(V) (March 8, 2021): 58–67. http://dx.doi.org/10.22610/jevr.v11i2(v).3135.
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Consumer perceptions of quality, satisfaction, and brand credibility are critical ingredients for developing healthy brands with high value in a competitive market. However, few authors have looked into the brand credibility`s intervening role in the effect of quality and satisfaction on brand equity in the non-conventional health industry. Hence, this paper sought to evaluate the mediating role of brand credibility in the effect of quality and satisfaction on brand equity in the non-conventional health industry. A covariance-based structural equation model was the analytical tool employed to evaluate the hypotheses stated in this paper. Data were gathered from 265 customers using a systematic sampling technique. The research confirmed that brand credibility contributes partially to the impact of quality on brand equity and completely to satisfaction on equity in the non-conventional health industry. Accordingly, this paper contributes to expanding the current brand management literature by demonstrating the brand credibility`s intervening role in the path between satisfaction, quality, and equity, particularly in the non-conventional health industry. This paper also adds to the brand manager`s knowledge of how to build and harness credibility, quality, and satisfaction to increase brand equity in the non-conventional health industry.
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Hill, Anita, Jorg Taubel, Jim Bush, Anna Borodovsky, Noriyuki Kawahata, Helen Mclean, Christine Powell, et al. "A Subcutaneously Administered Investigational RNAi Therapeutic (ALN-CC5) Targeting Complement C5 for Treatment of PNH and Complement-Mediated Diseases: Interim Phase 1 Study Results." Blood 126, no. 23 (December 3, 2015): 2413. http://dx.doi.org/10.1182/blood.v126.23.2413.2413.
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Abstract Introduction: Uncontrolled complement activation plays a pivotal role in a variety of disorders such as PNH and aHUS. ALN-CC5 is a subcutaneous (SC) investigational RNAi therapeutic targeting complement C5 (C5). In preclinical studies, ALN-CC5 has demonstrated decreased terminal complement activity. Based on the literature, preventing the generation of the terminal complex protects against intravascular hemolysis and complement-mediated tissue damage. The purpose of this study is to evaluate the safety and tolerability of ALN-CC5 in normal healthy volunteers. Material and methods: A multi-centered, placebo controlled, double blind phase 1 clinical study in healthy volunteers is ongoing. Several cohorts of healthy volunteers in Part A, a single ascending dose study and Part B, a weekly multiple ascending dose study have been completed. Primary endpoints are safety and tolerability. Secondary endpoints are pharmacokinetics, reduction of circulating C5, reduction in hemolytic, CAP and CCP activity. Results: In Part A, 20 healthy volunteers were randomized (1:3) to placebo or single SC dose of 50, 200, 400, 600 or 900mg of ALN-CC5 and followed for at least 70 days. In Part B, 12 healthy volunteers were randomized (1:3) to placebo or 5 weekly doses of 100, 200 or 400mg of ALN-CC5. No SAEs or study discontinuations occurred and overall ALN-CC5 was considered safe and generally well tolerated. A dose dependent and 94% mean maximum C5 knockdown was achieved following weekly administration. Updated safety and tolerability data as well as C5 knockdown, and changes in CAP, CCP and hemolytic activity from the study will be presented. Conclusion: Collectively, these initial results suggest that the use of a novel RNAi therapeutic targeting C5 is a promising approach for inhibiting complement in PNH, aHUS and other complement-mediated diseases. The subcutaneous route of administration and infrequent dosing make this a potentially encouraging therapy. Disclosures Hill: Alnylam: Consultancy. Off Label Use: ALN-CC5 is an investigational RNAi therapeutic targeting complement C5.. Borodovsky:Alnylam Pharmaceuticals: Employment, Equity Ownership. Kawahata:Alnylam Pharmaceuticals: Employment, Equity Ownership. Mclean:Alnylam Pharmaceuticals: Employment, Equity Ownership. Powell:Alnylam Pharmaceuticals: Employment, Equity Ownership. Chaturvedi:Alnylam Pharmaceuticals: Employment, Equity Ownership. Warner:Alnylam Pharmaceuticals: Employment, Equity Ownership. Garg:Alnylam Pharmaceuticals: Employment, Equity Ownership. Sorensen:Alnylam Pharmaceuticals: Employment, Equity Ownership.
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Poland, Blake, and Mark Dooris. "A green and healthy future: the settings approach to building health, equity and sustainability." Critical Public Health 20, no. 3 (August 25, 2010): 281–98. http://dx.doi.org/10.1080/09581596.2010.502931.
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Freeman, Toby, Matthew Fisher, Fran Baum, and Sharon Friel. "Healthy infrastructure: Australian National Broadband Network policy implementation and its importance to health equity." Information, Communication & Society 22, no. 10 (February 9, 2018): 1414–31. http://dx.doi.org/10.1080/1369118x.2018.1434555.
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Lithopoulos, Alexander, and Amy E. Latimer-Cheung. "An Experimental Application of the Brand Equity Pyramid Using a Healthy Movement Product Brand." Social Marketing Quarterly 26, no. 2 (June 2020): 129–45. http://dx.doi.org/10.1177/1524500420923352.
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Background: The brand equity pyramid is a theory that explains how people develop a relationship with a brand. Although the theory has received some support, few studies have tested it using a product brand, and no study has experimentally tested the theory. Research Question: The study tested whether brand equity pyramid variables pertaining to a health behavior promotion product brand (the Canadian 24-Hour Movement Guidelines for Children and Youth) can be experimentally manipulated. The first objective was to examine whether brand equity of the guidelines would be higher in the intervention group compared to the control group. The second objective was to explore whether parental attitudes and intentions toward support, support behaviors, and parent-perceived child behavior would be higher in the intervention group compared to the control. Method: Using an online survey platform in Canada, all participants first viewed the guidelines. Participants in the intervention group were then presented with a video targeting key brand equity variables, whereas the control group received no video. Participants were 161 Canadian parents ( M age = 38.17, SD = 7.33 years) with a child 5–12 years of age. Measurements of brand equity and behavioral variables were taken at Time 1 (immediately post-intervention) and 2 weeks later at Time 2. Results: The intervention group had greater brand awareness than the control group and also showed a more positive attitude toward ensuring their child is less sedentary. However, generally, the 1-time intervention had limited effects. Recommendations for Research or Practice: This study indicates that a single exposure to stimuli targeting brand equity constructs can enhance awareness and some proximal cognitions. Future studies should examine whether repeated exposures to brand advertisements result in change in more important, distal variables such as brand loyalty and actual behavior. Limitations: This study lacked a true baseline measurement time point, there was only one exposure to brand stimuli, and parent-perceived child behavior was measured rather than behavior reported by the children themselves.
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Christopher, Gail C. "Participatory Design and Research: Pathways to Healthy Communities and Racial Equity." Progress in Community Health Partnerships: Research, Education, and Action 6, no. 1 (2012): 1–3. http://dx.doi.org/10.1353/cpr.2012.0011.
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Roselle, René, and Chelsea Connery. "Food Justice: Access, Equity, and Sustainability for Healthy Students and Communities." Kappa Delta Pi Record 52, no. 4 (September 21, 2016): 174–77. http://dx.doi.org/10.1080/00228958.2016.1223993.
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KROGH, LENE. "Trends in town planning in the 1980s: equity and healthy planning." Health Promotion International 4, no. 2 (1989): 97–101. http://dx.doi.org/10.1093/heapro/4.2.97.
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Diehl, Jessica A., Debbie Heard, Steven Lockhart, and Deborah S. Main. "Access in the Food Environment: A Health Equity Approach Reveals Unequal Opportunity." Journal of Planning Education and Research 40, no. 1 (December 18, 2017): 69–81. http://dx.doi.org/10.1177/0739456x17745358.
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Evidence shows that not all places offer people equal access to affordable, healthy food; unequal access is a potential explanation for disparities in health. This study applied the theoretically grounded social science concept of health equity to shift the focus from equal (same for all) to equitable (needs-based) access. Using data from Taking Neighborhood Health to Heart (TNH2H), a large community-based participatory research (CBPR) initiative in Denver, Colorado, this article examines how food access can vary based on social advantage and disadvantage ( n = 926). Findings uncovered important inequities and demonstrated a new and promising approach to understanding the food environment–health relationship.
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Braithwaite, R. Scott, and Mark S. Roberts. "Are Discount Rates Too High? Population Health and Intergenerational Equity." Medical Decision Making 41, no. 2 (January 13, 2021): 245–49. http://dx.doi.org/10.1177/0272989x20979816.
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Increasing attention is being paid to policy decisions in which shorter-term benefits may be eclipsed by longer-term harms, such as environmental damage. Health policy decisions have largely been spared this scrutiny, even though they too may contribute to longer-term harms. Any healthy population or society must sustain itself through reproduction, and therefore, transgenerational outcomes should be of intrinsic importance from a societal perspective. Yet, the discount rates typically employed in cost-effectiveness analyses have the effect of minimizing the importance of transgenerational health outcomes. We argue that, because cost-effectiveness analysis is based on foundational axioms of decision theory, it should value transgenerational outcomes consistently with those axioms, which require discount rates substantially lower than 3%. We discuss why such lower rates may not violate the Cretin-Keeler paradox.
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Golden, Sherita Hill, Joshua J. Joseph, and Felicia Hill-Briggs. "Casting a Health Equity Lens on Endocrinology and Diabetes." Journal of Clinical Endocrinology & Metabolism 106, no. 4 (January 18, 2021): e1909-e1916. http://dx.doi.org/10.1210/clinem/dgaa938.
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Abstract As endocrinologists we have focused on biological contributors to disparities in diabetes, obesity and other endocrine disorders. Given that diabetes is an exemplar health disparity condition, we, as a specialty, are also positioned to view the contributing factors and solutions more broadly. This will give us agency in contributing to health system, public health, and policy-level interventions to address the structural and institutional racism embedded in our medical and social systems. A history of unconsented medical and research experimentation on vulnerable groups and perpetuation of eugenics theory in the early 20th century have resulted in residual health care provider biases toward minority patients and patient distrust of medical systems, leading to poor quality of care. Historical discriminatory housing and lending policies resulted in racial residential segregation and neighborhoods with inadequate housing, healthy food access, and educational resources, setting the foundation for the social determinants of health (SDOH) contributing to present-day disparities. To reduce these disparities we need to ensure our health systems are implementing the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care to promote health equity. Because of racial biases inherent in our medical systems due to historical unethical practices in minority communities, health care provider training should incorporate awareness of unconscious bias, antiracism, and the value of diversity. Finally, we must also address poverty-related SDOH (eg, food and housing insecurity) by integrating social needs into medical care and using our voices to advocate for social policies that redress SDOH and restore environmental justice.
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Meyer-Abich, Klaus Michael. "Human health in nature – towards a holistic philosophy of nutrition." Public Health Nutrition 8, no. 6a (September 2005): 738–42. http://dx.doi.org/10.1079/phn2005788.
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AbstractObjectiveTo explain how the philosophy of nutrition is part of the philosophy of health. To show that this link allows practical solutions for equity and sustainability.MethodAn analysis of the historical philosophies concerned with nutrition and health. A comparison of the definitions in the history of mind from antiquity to the beginning of the twenty-first century.ConclusionWe are not individually healthy, but we are so in togetherness, even with animals and plants. Comprehensive nutrition science has physical, social and environmental attributes. It follows that nutrition is good for the enhancement of good company with human beings as well as with the connatural world. We recognise that we owe to others what we are and this constitutes the equity of being.
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Lee, Munjae, and Kichan Yoon. "Effects of the Health Promotion Programs on Happiness." Sustainability 12, no. 2 (January 10, 2020): 528. http://dx.doi.org/10.3390/su12020528.
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The Healthy City program is a comprehensive health promotion program implemented by local governments to improve citizens’ health. The Healthy City program aims to improve citizens’ quality of life through health promotion activities in daily life. It also improves health by eliminating health risk factors and increasing citizens’ happiness. Therefore, this study investigated the effects of the Healthy City program on the happiness index of local residents and the correlation between the Healthy City program and the happiness index using quality of life as a parameter. We conducted a questionnaire survey of residents of Seoul, where Healthy City networks are actively promoted. A total of 392 responses were obtained. Structural equations were used to analyze the collected data. The Healthy City program had positive effects on the happiness index. In other words, it increased the happiness index by improving the health of the local residents. Relevant policy efforts are also being made to advance health services through Healthy City programs. For an effective Healthy City program, it is necessary to implement policies regarding health equity, to expand Healthy City programs based on a settings approach, and to implement a sustainable Healthy City program through the establishment of Healthy City governance.
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Zhang, Xinyuan, Zhixiu Guo, Xiaorui Feng, and Yan He. "Study on Relation between Equity Structure and Performance of Listed Companies - Evidence for Building Industry in A Share Market." International Journal of Economics and Finance 9, no. 7 (June 12, 2017): 114. http://dx.doi.org/10.5539/ijef.v9n7p114.
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The equity structure is the basis for corporate governance, and the decisive factor for performance of listed companies. Considering the return on equity as the measure index of company performance, the paper has collected 2014-2016 data related to index of equity structure from 32 listed companies in Shanghai and Shenzhen, made descriptive statistical analysis and correlation analysis on it with spass20.0 statistical software, and discussed the relation between equity structure and performance of listed companies. The research finds that: Chinese listed companies for building industry still have relatively high equity concentration, imperfect internal governance mechanism and poor equity restriction. The effect of “bargaining” is difficultly developed to promote the growth of performance. China shall further strengthen the efforts to control, spur listed companies to reinforce the internal management, and optimize the equity structure to ensure the effective balance, with the purpose of accelerating the healthy and sustainable development of listed companies and safeguarding the interests of medium-small investors.
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Trefry, Sharonlee. "Health and Academic Equity in Schools: Is Nursing Far Enough Up Stream?" NASN School Nurse 35, no. 2 (November 21, 2019): 79–81. http://dx.doi.org/10.1177/1942602x19885956.
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When the Robert Wood Johnson Foundation in partnership with the National Academy of Medicine announced the Town Meeting discussions of the Future of Nursing 2030, the president of the National Association of State School Nurse Consultants felt that the voice of School Nursing was crucial to informing the national discussion on health equity and health promotion. Sharonlee Trefry, State School Nurse Consultant, wanted to be sure that the leadership team of the Future of Nursing 2030 heard about the needs of the nation’s 56.6 million elementary and secondary public and independent school students. Serving in an even greater role today with regard to promoting equity in healthcare and educational access, school nurses recognize and address social determinants of health every day all day working to grow the next generation of healthy citizens.
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Semlow, Andrea R., Jennifer M. Ellison, Emily C. Jaeger, and Derek M. Griffith. "Healthy Men 2030: Setting Men’s Health Goals as a Tool to Improve the Nation’s Health and Achieve Health Equity." Health Education & Behavior 48, no. 4 (July 13, 2021): 393–96. http://dx.doi.org/10.1177/10901981211025465.
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Sadana, Ritu, Erik Blas, Suman Budhwani, Theadora Koller, and Guillermo Paraje. "Healthy Ageing: Raising Awareness of Inequalities, Determinants, and What Could Be Done to Improve Health Equity." Gerontologist 56, Suppl 2 (March 18, 2016): S178—S193. http://dx.doi.org/10.1093/geront/gnw034.
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Lincoln, Karen. "Best of Both Worlds: Bridging Research and Practice to Achieve Health Equity." Innovation in Aging 4, Supplement_1 (December 1, 2020): 867. http://dx.doi.org/10.1093/geroni/igaa057.3204.
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Abstract Health inequity is linked to societal and social determinants that constrain health promoting opportunities for older adults. From birth to death, many older adults contend with the prevailing social and health effects of discrimination in employment, education, and housing. As a consequence, middle-aged Black Americans are experiencing accelerated aging, and living with and dying from preventable chronic health conditions typically diagnosed at older ages. Despite these conditions, there is much variation in health outcomes among older Black Americans. Professor Karen Lincoln will share her approach to research that explores heterogeneity within the Black American population to discover factors that promote healthy aging. She will describe her unique outreach and health education program that serves older adults in underserved communities, and her roles as an aging advocate and public scholar. She will discuss how these experiences led to the development and testing of an innovative intervention to reduce Alzheimer’s disease disparities.
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Sangkhae, Veena, Tomas Ganz, and Elizabeta Nemeth. "Maternal Hepcidin Suppression Is Essential for Healthy Pregnancy." Blood 136, Supplement 1 (November 5, 2020): 43–44. http://dx.doi.org/10.1182/blood-2020-141148.
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Iron is essential for maternal and fetal health during pregnancy, and iron requirements increase substantially in the second half of gestation1. However, the molecular mechanisms ensuring increased iron availability during pregnancy are not well understood. Hepcidin is the key iron-regulatory hormone and functions by occluding and degrading the iron exporter ferroportin (FPN) to inhibit dietary iron absorption and mobilization of iron from stores. In healthy human and rodent pregnancies, maternal hepcidin decreases starting in the second trimester and is nearly undetectable by late pregnancy2,3 (Figure A). We explored the role of maternal and embryo hepcidin in regulating embryo iron endowment using mouse models. By generating combinations of dams and embryos lacking hepcidin or not, we showed that in normal mouse pregnancy, only maternal but not embryo or placental hepcidin determines embryo iron endowment4. Maternal hepcidin was inversely related to embryo iron stores, and embryos from hepcidin-deficient dams had significantly higher hepatic iron stores regardless of their own hepcidin genotype. When maternal hepcidin was elevated during the second half of pregnancy in mice by administering a hepcidin mimetic, this led to dose-dependent embryo iron deficiency, anemia, and in severe cases, embryo death4. Embryos were particularly sensitive to maternal iron restriction as they developed iron deficiency in the liver and the brain even when maternal hematological parameters were unaffected. These data highlight the critical role of maternal hepcidin suppression for heathy pregnancy. Yet, the physiological mechanism of maternal hepcidin suppression remains unknown. We showed in mice that maternal hepcidin decreases prior to a significant decrease in liver iron and without any changes in serum iron, suggesting that maternal hepcidin suppression is not driven solely by iron deficiency. Using an in vitro model, we determined that the placenta secretes a hepcidin-suppressing factor. Exposure of primary mouse hepatocytes to supernatants from cultured human placenta cells, but not control media, suppressed hepcidin mRNA more than 10-fold (Figure B) and for up to 48hrs. The suppressive factor in the supernatant was >100kDa in size and not associated with exosomes. Studies to identify the placenta-derived hepcidin suppressor are ongoing. In summary, suppression of maternal hepcidin is essential to ensure adequate iron supply for transfer to the fetus and for the increase in maternal red blood cell mass2, and a placenta-derived hepcidin suppressor likely plays an important role in this adaptation. 1Fisher AL and Nemeth E, Am J Clin Nutr, 2017 2Sangkhae V et al, JCI, 2020 3van Santen S et al, Clin Chem Lab Med, 2013 4Sangkhae V et al, Blood, 2020 Figure 1 Disclosures Ganz: Global Blood Therapeutics: Consultancy; Ionis Pharmaceuticals: Consultancy; American Regent: Consultancy; Rockwell: Consultancy; Vifor: Consultancy; Astellas: Consultancy; Akebia: Consultancy; Gossamer Bio: Consultancy; Silarus Therapeutics: Current equity holder in private company; Sierra Oncology: Consultancy; Ambys: Consultancy; Disc Medicine: Consultancy; Intrinsic LifeSciences: Current equity holder in private company. Nemeth:Intrinsic LifeSciences: Current equity holder in private company; Silarus Therapeutics: Current equity holder in private company; Ionis Pharmaceuticals: Consultancy; Protagonist: Consultancy; Vifor: Consultancy.
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McGowan, Angela K., K. T. Kramer, and Joel B. Teitelbaum. "Healthy People: The Role of Law and Policy in the Nation's Public Health Agenda." Journal of Law, Medicine & Ethics 47, S2 (2019): 63–67. http://dx.doi.org/10.1177/1073110519857320.
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Each decade since 1979, the Healthy People initiative establishes the national prevention agenda and provides the foundation for disease prevention and health promotion policies and programs. Law and policy have been included in Healthy People objectives from the start, but not integrated into the overall initiative as well as possible to potentially leverage change to meet Healthy People targets and goals. This article provides background on the Healthy People initiative and its use among various stakeholder groups, describes the work of a project aiming to better integrate law and policy into this initiative, and discusses the development of Healthy People 2030 — the next iteration of health goals for the nation. Lessons from the preliminary stages of developing Healthy People by the HHS Secretary's Advisory Committee (Committee) on National Health Promotion and Disease Prevention Objectives for 2030 and a Federal Interagency Workgroup will be included. Efforts by the Committee focused on the role of law and policy as determinants of health and valuable resources around health equity are also shared. Finally, the article discusses ways that law and policy can potentially be tools to help meet Healthy People targets and to attain national health goals.
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Chubukov, Victor, Kendall Johnson, Penelope A. Kosinski, Michelle Clasquin, Abhishek Jha, Hyeryun Kim, Thomas P. Roddy, et al. "Characterization of Metabolic Response to AG-348, an Allosteric Activator of Red Cell Pyruvate Kinase, in Healthy Volunteers and Pyruvate Kinase Deficiency Patients." Blood 128, no. 22 (December 2, 2016): 2452. http://dx.doi.org/10.1182/blood.v128.22.2452.2452.
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Abstract Pyruvate kinase (PK) deficiency is a glycolytic enzymopathy that causes lifelong chronic hemolytic anemia. AG-348 is an allosteric activator of the red cell isoform of pyruvate kinase (PK-R) that is in clinical development to treat PK deficiency. Phase 1 studies of AG-348 in healthy volunteers (NCT02108106, NCT02149966) have been completed, and a phase 2 study in patients with PK deficiency is in progress (DRIVE PK, NCT02476916). We have previously reported that in the healthy volunteer studies, AG-348 induced changes in levels of the metabolites adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) that are consistent with PK-R activation. A preliminary analysis of data showed that nine out of 18 DRIVE PK patients achieved a maximal increase in hemoglobin (Hb) levels of >1.0 g/dL. In this study, we characterize whole blood metabolism of healthy human subjects (from the multiple-ascending dose study NCT02149966) as well as PK-deficient patients (from DRIVE PK), before and after administration of AG-348, with a focus on the flux through the PK-R reaction. Whole blood taken from healthy subjects/DRIVE PK patients on each respective study was incubated with a stable isotope tracer, [U-13C6]-glucose. Glycolytic flux through PK-R was estimated by kinetic flux profiling based on the isotope labeling, as well as by the specific lactate production rate, with the two methods giving consistent results. Blood cells from healthy subjects exhibited classic red blood cell (RBC) metabolism, with the majority of glucose catabolized through glycolysis. AG-348 was shown to significantly increase the maximal PK-R protein activity in these subjects, and also to have metabolic effects consistent with PK-R activation, marked by decreased concentrations of glycolytic intermediates such as 2,3-DPG and phosphoenolpyruvate (PEP). Increases in ATP concentrations were also observed, with the magnitude and kinetics of the increase strongly suggesting enhanced adenosine salvage or synthesis. The overall glycolytic rates, however, did not change significantly after two weeks of AG-348 dosing, revealing the homeostatic regulation of RBC glycolysis in healthy blood. Five of the first 18 DRIVE PK patients underwent an extensive sampling protocol for metabolic analysis. This analysis revealed a number of distinct metabolic qualities in PK-deficient patients at baseline compared with healthy subjects. These included significantly reduced rates of lactate production and high concentrations of nucleotides, amino acids, and Krebs cycle intermediates. 13C labeling was observed in Krebs cycle intermediates, demonstrating significant respiratory metabolism in whole blood cells from PK-deficient patients, while incomplete labeling of glycolytic intermediates suggested the presence of a metabolically inactive cell subpopulation. These observations are most consistent with the hypothesis that PK-deficient whole blood is dominated metabolically by immature erythrocytes that retain residual mitochondrial activity. With AG-348 treatment, three of the five DRIVE PK patients had increases in Hb of >1.0 g/dL. In those three patients, we observed increased incorporation of 13C label into glycolytic intermediates such as 2,3-DPG, suggesting an increase in metabolically active erythrocytes. First order flux estimates based on either 2,3-DPG labeling kinetics or lactate production rates showed a >0.1 mmol/L/hr (>50%) increase in glycolytic flux. Neither of the two DRIVE PK patients that did not have an Hb increase of >1.0 g/dL showed significant metabolic changes. In conclusion, metabolic profiling and stable isotope tracing experiments in blood from healthy subjects treated with AG-348 revealed strong homeostatic regulation of glycolysis even in the presence of activated PK-R. Analysis of data from a small number (n=5) of PK-deficient patients treated with AG-348 for two weeks showed that the three patients with Hb increases >1.0 g/dL also had increased glycolytic flux. While the small number of patients makes these results preliminary, it is the first demonstration of a direct link between increased red cell glycolysis induced by the PK-R activator AG-348 and the resulting hematological response as assessed by increases in Hb levels. Updated analyses including additional patients will be presented as more data are collected in the ongoing study. Disclosures Chubukov: Agios Pharmaceuticals, Inc.: Employment, Equity Ownership. Johnson:Agios Pharmaceuticals, Inc.: Employment, Equity Ownership. Kosinski:Agios Pharmaceuticals, Inc.: Employment, Equity Ownership. Clasquin:Agios Pharmaceuticals, Inc.: Other: former employee and stock holder; Pfizer, Inc.: Employment. Jha:Agios Pharmaceuticals, Inc.: Employment, Equity Ownership. Kim:Agios Pharmaceuticals, Inc.: Employment, Equity Ownership. Roddy:Agios Pharmaceuticals, Inc.: Employment, Equity Ownership. Merica:Agios Pharmaceuticals, Inc.: Employment, Equity Ownership. Barbier:Agios Pharmaceuticals, Inc.: Employment, Equity Ownership. Dang:Agios Pharmaceuticals, Inc.: Employment, Equity Ownership. Silverman:Agios Pharmaceuticals, Inc.: Employment, Equity Ownership. Kung:Agios Pharmaceuticals, Inc.: Employment, Equity Ownership.
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Musselwhite, Laura W., Folasade P. May, Mohamed E. Salem, and Edith P. Mitchell. "Colorectal Cancer: In the Pursuit of Health Equity." American Society of Clinical Oncology Educational Book, no. 41 (March 2021): 108–17. http://dx.doi.org/10.1200/edbk_321071.
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Colorectal cancer mortality has decreased considerably following the adoption of national screening programs, yet, within at-risk subgroups, there continue to be measurable differences in clinical outcomes from variations in screening, receipt of chemotherapy, radiation or surgery, access to clinical trials, research participation, and survivorship. These disparities are well-described and some have worsened over time. Disparities identified have included race and ethnicity, age (specifically young adults), socioeconomic status, insurance access, geography, and environmental exposures. In the context of the COVID-19 pandemic, colorectal cancer care has necessarily shifted dramatically, with broad, immediate uptake of telemedicine, transition to oral medications when feasible, and considerations for sequence of treatment. However, it has additionally marginalized patients with colorectal cancer with historically disparate cancer-specific outcomes; among them, uninsured, low-income, immigrant, and ethnic-minority patients—all of whom are more likely to become infected, be hospitalized, and die of either COVID-19 or colorectal cancer. Herein, we outline measurable disparities, review implemented solutions, and define strategies toward ensuring that all have a fair and just opportunity to be as healthy as possible.
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Indriani, Rina, and Hakiman Thamrin. "MODEL OF BANKRUPTCY PREDICTION SERVICES COMPANY SECTOR RETAIL IN INDONESIA STOCK EXCHANGE (Study Case Period 2015 - 2017)." Dinasti International Journal of Digital Business Management 1, no. 2 (February 6, 2020): 142–53. http://dx.doi.org/10.31933/dijdbm.v1i2.129.
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This study aims to identify the dominant causes in forming a bankruptcy prediction model of retail trade service companies listed on the Indonesia Stock Exchange in the 2015-2017 period. The 2015-2017 observation period with a sample of 20 companies met the criteria as a sample. This research variable is divided into 2 namely dependent and independent variables. The dependent variable in this study is categorical data which is divided into two categories: unhealthy companies symbolized by the number 0 and healthy companies category symbolized by the number 1. The independent variables in this study are 20 financial ratios, among others, Current Ratio, Quick Ratio, Cash Ratio , Working Capital to Total Assets, Debt to Asset Ratio, Debt to Equity Ratio, Time Interest Earned, Working Capital Turn Over, Fixed Asset Turn Over, Receivable Turn Over, Total Asset Turn Over, Inventory Turn Over, Cash Turn Over, Cash Profit Margin, Operating Profit Margin, Gross Profit Margin, Return On Equity, Return On Assets, Return On Investment, Earning Per Share. The analytical method used is discriminant analysis. Discriminant Test Results using the stepwise method can be obtained variables that are selected as discriminator variables, namely the variable Debt to Equity Ratio, Return On Equity, and Earning Per Share to form discriminant functions as follows: R = - 3,197 + 0.292 Debt to Equity Ratio + 0.342 Return On Equity + 0.336 Earning Per Share The cut-off value in this study is 0 with a 75% prediction accuracy in unhealthy service companies and 73.3% in healthy service companies with an accuracy rate of 76.7% in retail trade service companies.
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Fahn, Matthias, Valeria Merlo, and Georg Wamser. "The Commitment Role of Equity Financing." Journal of the European Economic Association 17, no. 4 (July 3, 2018): 1232–60. http://dx.doi.org/10.1093/jeea/jvy026.
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Abstract Existing theories of a firm’s optimal capital structure seem to fail in explaining why many healthy and profitable firms rely heavily on equity financing, even though benefits associated with debt (like tax shields) appear to be high and the bankruptcy risk low. This holds in particular for firms that show a strong commitment toward their workforce and are popular among employees. We demonstrate that such financing behavior may be driven by implicit arrangements made between a firm and its managers/employees. Equity financing generally strengthens a firm’s credibility to honor implicit promises. Debt, however, has an adverse effect on the enforceability of these arrangements because too much debt increases the firm’s reneging temptation, as some of the negative consequences of breaking implicit promises can be shifted to creditors. Our analysis provides an explanation for why some firms only use little debt financing. Predictions made by our theory are in line with a number of empirical results, which seem to stay in contrast to existing theories on capital structure.
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Marmot, Michael. "Closing the health gap." Scandinavian Journal of Public Health 45, no. 7 (November 2017): 723–31. http://dx.doi.org/10.1177/1403494817717433.
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One way of characterising the good society is one that has achieved a high degree of health equity. For a low-income country, one route to this achievement is to increase national income. But other features of society come to the fore, for low, middle and high-income societies alike. In England, my review of health inequalities highlighted: good early child development, education and life long learning, employment and working conditions, having enough income to lead a healthy life, healthy and sustainable places to live and work, taking a social determinants approach to prevention. Taking action on these requires commitment and cross-government action.
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Buzeti, Tatjana, Joana Madureira Lima, Lin Yang, and Chris Brown. "Leaving no one behind: health equity as a catalyst for the sustainable development goals." European Journal of Public Health 30, Supplement_1 (March 1, 2020): i24—i27. http://dx.doi.org/10.1093/eurpub/ckaa033.
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Abstract 2019 has been a milestone year for catalyzing changes to improve health equity in the WHO European Region through concomitant progress in the sustainable development goal (SDG) targets. The WHO European Health Equity Status Report Initiative (HESRi) has captured and analyzed the relationships between inequities in health and the conditions that are essential for all to be able to live healthy and prosperous lives. The five essential conditions map directly onto a number of SDG targets, with a much broader span than SDG3 on health. They are: (i) Universal access to good-quality, affordable health services; (ii) Basic income security and social protection; (iii) Safe and decent living conditions; (iv) Inclusive social and human capital building opportunities; and (v) Decent and non-discriminatory employment and working conditions. There is certainly room for improvement in the way ahead, particularly in the availability of fine-grained and disaggregated data, and in the quality of monitoring and analysis of policy options that this would allow. However, the work of the HESRi shows that by harnessing such data it is possible to show what actions policymakers can take in the present to ensure that no one is left behind. This equity framing allows to measure whether the progress on SDGs benefits all, including those who need them most.
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Pemu, Priscilla, Robina Josiah Willock, Ernest Alema-Mensah, Latrice Rollins, Michelle Brown, Bethany Saint Clair, Elizabeth Olorundare, et al. "Achieving Health Equity with e-Healthystrides©: Patient Perspectives of a Consumer Health Information Technology Application." Ethnicity & Disease 29, Supp2 (June 13, 2019): 393–404. http://dx.doi.org/10.18865/ed.29.s2.393.
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Objective: We describe the implementation, clinical outcomes and participant perspectives for e-Healthystrides©.Setting: Three independent ambulatory clinics and an historic African American (AA) church.Participants: Adults with diagnosed diabetes mellitus type 2.Interventions: e-Healthystrides© health coach facilitated interventionPrimary outcome: Acquisition of three new self-management behaviors.Secondary outcomes: Blood pressure, blood glucose, A1c, attrition rate and participant perspectives of e-Healthystrides©Methods: A convergent parallel mixed method design was used in both pilot studies.Results: Two hundred and sixty-four participants, aged ~62±16 years, enrolled. Attrition at 52 weeks varied 50%-90% by site. Low engagement users were defined mainly by anxiety with putting health information online. The primary outcome was achieved in 36% of our participants, with the top 3 self-management behaviors acquired being: reducing risk (24.5%); healthy eating (23.7%); and monitoring (16.4%). Problem solving had the lowest rate of achievement (.91%). Blood pressure improved significantly at all sites at 12 weeks and at clinics A,B,C at 52 weeks. Blood glucose improved at 12 weeks: clinic A (P=.0001), B (P=.003), C (P=.001) and D (P=.03); but, at 52 weeks, only clinics A (P=<.0001) and B (P=.0001). Participants felt empowered by features of e-Healthystrides©. Engagement with health coaches and peers was highly valued.Conclusions: e-Healthystrides© is effective for self-management behavior change. Participants showed the best success with healthy coping, healthy eating, and monitoring behaviors. They felt empowered by access to health information and valued interaction with coaches and peers. Our findings support strong relational/social network strategy with a role for coaches as guides (apomediaries) who facilitate skill acquisition using technology. Ethn Dis. 2019;29(Suppl 2):393-404; doi:10.18865/ed.29.S2.393.
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deValpine, Maria Gilson, and Laura Hunt Trull. "Health Equity in Community Assessments: A Participatory Approach in Rural Virginia." SAGE Open 9, no. 1 (January 2019): 215824401983892. http://dx.doi.org/10.1177/2158244019838925.
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A coalition of community members and human service professionals in the rural central Shenandoah Valley of Virginia has performed a community assessment every 5 years. Overreliance on quantitative surveys and hospital-based Community Health Needs Assessments resulted in earlier assessments failing to identify the needs of vulnerable populations. As the coalition approached the time for a new assessment, their priority was to develop a deeper understanding of community health needs and solutions. An extended co-learning process between coalition, community, and local academic representatives resulted in a plan to develop assessment methods and community health improvement resources suited to this goal. The coalition identified methods rooted in the social determinants of health and utilized a community-based participatory research approach to provide underserved residents the opportunity to contribute to health research and decision making and produce an assessment more reflective of their community. Resources including local interpretation and implications of the World Health Organization’s 10 Social Determinants of Health, a Healthy People 2020 community health services profile, and user-friendly access to community-based secondary data sets were developed for intervention planning. All information, resources, and implications were shared at meetings, in public announcements, and at a public forum. All data remain publicly available on the coalition’s website. Previously held beliefs regarding access to care and quality of life were substantiated through this process, enabling the coalition to better align itself with local political entities and to move forward immediately with community health improvement planning.
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Buse, Kent, Wafa Aftab, Sadika Akhter, Linh Bui Phuong, Haroun Chemli, Minakshi Dahal, Anam Feroz, et al. "The state of diet-related NCD policies in Afghanistan, Bangladesh, Nepal, Pakistan, Tunisia and Vietnam: a comparative assessment that introduces a ‘policy cube’ approach." Health Policy and Planning 35, no. 5 (February 24, 2020): 503–21. http://dx.doi.org/10.1093/heapol/czz175.
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Abstract We assessed the technical content of sugar, salt and trans-fats policies in six countries in relation to the World Health Organization ‘Best Buys’ guidelines for the prevention and control of non-communicable diseases (NCDs). National research teams identified policies and strategies related to promoting healthy diets and restricting unhealthy consumption, including national legislation, development plans and strategies and health sector-related policies and plans. We identified relevant text in relation to the issuing agency, overarching aims, goals, targets and timeframes, specific policy measures and actions, accountability systems, budgets, responsiveness to inequitable vulnerabilities across population groups (including gender) and human rights. We captured findings in a ‘policy cube’ incorporating three dimensions: policy comprehensiveness, political salience and effectiveness of means of implementation, and equity/rights. We compared diet-related NCD policies to human immunodeficiency virus policies in relation to rights, gender and health equity. All six countries have made high-level commitments to address NCDs, but dietary NCDs policies vary and tend to be underdeveloped in terms of the specificity of targets and means of achieving them. There is patchwork reference to internationally recognized, evidence-informed technical interventions and a tendency to focus on interventions that will encounter least resistance, e.g. behaviour change communication in contrast to addressing food reformulation, taxation, subsidies and promotion/marketing. Policies are frequently at the lower end of the authoritativeness spectrum and have few identified budgetary commitments or clear accountability mechanisms. Of concern is the limited recognition of equity and rights-based approaches. Healthy diet policies in these countries do not match the severity of the NCDs burden nor are they designed in such a way that government action will focus on the most critical dietary drivers and population groups at risk. We propose a series of recommendations to expand policy cubes in each of the countries by re-orienting diet-related policies so as to ensure healthy diets for all.
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Sebayang, Pirmanta. "The Impact of the Capital Adequacy Ratio, Non-Performing Loan Against to Return on Equity (Case Study Private Bank in Indonesia)." SHS Web of Conferences 76 (2020): 01035. http://dx.doi.org/10.1051/shsconf/20207601035.
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Banks in Indonesia always pay attention to the Capital Adequacy Ratio (CAR) to obtain adequate bank performance, while also paying attention to Non-Performing Loan (NPL). Banks want a high Return on Equity (ROE) to be able to be declared healthy and the bank's performance is also very good. Banking companies always make financial reports related to the banking performance. This study has two objectives namely, first to examine the effect of Capital Adequacy Ratio (CAR) on Return on Equity (ROE). Second, to examine the effect of Non-Performing Loans (NPLs) on Return on Equity (ROE) in foreign private banks that have been determined by the government. This study uses multiple regression analysis techniques using a sample of 20 banks. The test results show that there is an increase in capital Adequacy Ratio (CAR) that will be able to increase the Return on Equity (ROE) of foreign private banks in Indonesia. Increased Non-Performing Loans (NPLs) can have a positive effect and increase Return on Equity (ROE). Simultaneous tests carried out obtained the variable Adequacy Ratio (CAR) and Return on Equity (ROE) to have a joint impact on the Return on Equity (ROE) of private banks.
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Le, Kha, Marvin Cohen, Yue Chen, Hyeryun Kim, Bruce Silver, Sam Agresta, Elizabeth Merica, et al. "Population Pharmacokinetics and Pharmacodynamics of AG-348 in Healthy Human Volunteers Guide Dose Selection for the Treatment of Pyruvate Kinase Deficiency." Blood 126, no. 23 (December 3, 2015): 3336. http://dx.doi.org/10.1182/blood.v126.23.3336.3336.
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Abstract INTRODUCTION: Pyruvate kinase (PK) deficiency is a glycolytic enzymopathy that results in non-spherocytic hemolytic anemia with a variable clinical presentation, ranging from mild or fully compensated forms to life-threatening neonatal anemia and life-long chronic hemolytic anemia associated with severe, debilitating co-morbidities. PK deficiency is caused by mutations in the PKLR gene, which in the red blood cell (RBC) results in defective pyruvate kinase isoform R (PK-R). PK-R catalyzes the final, irreversible step in glycolysis, the process on which mature RBCs rely almost exclusively to generate the energy carrier molecule adenosine triphosphate (ATP). PK-deficient RBCs and their progenitors are characterized by changes in metabolism associated with defective glycolysis, including a build-up of phosphoenolpyruvate (PEP) and 2,3-diphosphoglycerate (2,3-DPG), and lowered ATP levels. AG-348 is an orally available, allosteric activator of PK-R. It is hypothesized that intervention with AG-348 restores glycolytic pathway activity and normalizes RBC metabolism in vivo (Kung C et al. Blood, 2013). Biochemical experiments demonstrate that AG-348 is a potent pan-activator of many PK-R alleles associated with PK deficiency. Treatment of PK-deficient patient RBCs ex vivo with AG-348 results in increased ATP levels, and reductions in PEP and 2,3-DPG, consistent with pharmacological activation of the PK-R enzyme. This analysis integrates the pharmacokinetic and pharmacodynamic (PK/PD) properties of AG-348 in healthy human volunteers using population PK/PD modeling and simulation. METHODS: PK/PD modeling using a non-linear mixed effects approach was performed to understand the pharmacokinetics of AG-348 and PK/PD relationship of AG-348 to 2,3-DPG and ATP in humans. The PK/PD model integrated data from two phase 1, single-center, randomized, double-blind, placebo-controlled, dose escalation studies (one single and one 14-day multiple ascending dose) that enrolled a total of 96 healthy volunteers (Yang H et al. EHA Learning Center, 2015). AG-348 dose level ranged from 15-2500 mg given once (QD) or twice (BID) daily. Blood was collected from all patients to assess AG-348 pharmacokinetics, and for determination of levels of ATP and 2,3-DPG. Population simulations using the final model were performed to examine the dose-exposure-biomarkers relationship at various dose levels and duration of dosing. RESULTS: AG-348 showed rapid absorption following oral administration. Plasma exposure of AG-348 increased in a dose-proportional manner following a single dose. A three-compartmental model with a non-linear absorption compartment and a saturable induced enzyme compartment best described the pharmacokinetics of AG-348. Time-varying clearance was added to describe the observed decrease in exposure over time with multiple dosing; this is consistent with pre-clinical data that AG-348 is a moderate inducer of CYP3A4, the major oxidation pathway of AG-348. The multiple-dose data were well described by a semi-mechanistic autoinduction model with an indirect model and a saturable induction compartment. The PK/PD relationship between plasma AG-348 to ATP and 2,3-DPG showed best fit with a turnover model where the drug effect was described by an Emax model. Model simulations predicted maximum enzyme induction and PD response 3 weeks after the first dose following BID dosing. Population PK/PD simulations further supported the choice of 50 mg and 300 mg BID doses for the phase 2 study (Fig 1 and 2). The proposed current model incorporating PK/PD data over a wide range of AG-348 exposures and time-varying changes in clearance provides a useful tool for prediction of AG-348 pharmacokinetics that can be used to optimize AG-348 dosing for PK deficiency treatment. Furthermore, the population PK/PD model of AG-348 to ATP and 2,3-DPG biomarkers in healthy volunteers provides a good foundation to facilitate the analysis and understanding of patient data in the ongoing phase 2 study. CONCLUSION: This study represents the first comprehensive longitudinal analysis of AG-348 and its PD activity in humans. This integrated PK/PD model, incorporating time-varying PK/PD properties, forms the basis for understanding the exposure-response relationship in the ongoing phase 2 and future clinical studies of AG-348, as well as providing guidance on dosing selection to optimize the treatment of PK deficiency. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Le: Agios Pharmceuticals: Employment, Equity Ownership. Cohen:Agios: Consultancy. Chen:Agios: Employment. Kim:Agios: Employment. Silver:Agios: Consultancy. Agresta:Agios: Employment, Equity Ownership. Merica:Agios Pharmaceuticals: Employment, Equity Ownership. Kung:Agios: Employment, Equity Ownership. Kosinski:Agios: Employment, Equity Ownership; General Electric: Equity Ownership; SDIX: Equity Ownership. Silverman:Agios: Employment, Equity Ownership. Biller:Agios Pharmaceuticals: Employment, Equity Ownership; Arbutus BioPharma (formerly Tekmira): Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Syros Pharmaceuticals: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Arvinas: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Denali: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Yang:Agios Pharmaceuticals: Employment, Equity Ownership.
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Evans, Erica, Richland Tester, Sharon Aslanian, Prasoon Chaturvedi, Hormoz Mazdiyasni, Sabine Ponader, Bethany Tesar, et al. "Clinical Development of AVL-292; A Potent, Selective Covalent Btk Inhibitor for the Treatment of B Cell Malignancies,." Blood 118, no. 21 (November 18, 2011): 3485. http://dx.doi.org/10.1182/blood.v118.21.3485.3485.
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Abstract Abstract 3485 Targeted therapies that suppress B cell receptor (BCR) signaling have emerged as promising agents in the treatment of several B cell malignancies. Bruton's tyrosine kinase (Btk) plays a key role in promoting B cell proliferation and survival through participation in the BCR signaling pathway and represents a promising new drug target. AVL-292 is a covalent, highly selective, orally active small molecule inhibitor of Btk currently being evaluated in a Phase 1b clinical trial in relapsed, refractory B cell malignancies including Chronic Lymphocytic Leukemia (CLL) and non-Hodgkin lymphomas. AVL-292 forms a covalent bond with Cys481 in Btk and potently inhibits Btk in biochemical (IC50 < 0.5nM) and cellular assays (EC50 1–10 nM) including anti-IgM stimulation of BCR signaling, B cell proliferation and activation. A quantitative pharmacodynamic assay to determine the level of AVL-292 bonded to Btk in vitro or in vivo was developed and this drug-target engagement by AVL-292 was shown to correlate directly with inhibition of Btk enzyme activity and substrate phosphorylation. To rationally determine the dose and dose frequency of AVL-292 most likely to benefit patients and to reduce the potential for sub-therapeutic dosing in initial oncology patient cohorts, AVL-292 was administered to healthy adult subjects in a double-blind, placebo controlled, single ascending dose study. This study assessed safety, pharmacokinetics, and quantitatively measured Btk protein levels and AVL-292-Btk engagement in freshly isolated peripheral B lymphocytes. In healthy human subjects, AVL-292 was found to be safe and well tolerated following oral administration at dose levels ranging from 0.5–7.0 mg/kg. AVL-292 plasma levels and pharmacodynamic measurement of Btk engagement was dose-proportional across cohorts. All subjects that received 1.0 mg/kg AVL-292 achieved >80% Btk engagement and mean peak plasma levels (Cmax 365 ng/mL) of AVL-292 were rapidly achieved (Tmax median 40 min). Subjects receiving 2.0 mg/kg AVL-292 had a mean peak plasma concentration of 542 ng/mL. All subjects demonstrated >84% Btk engagement at this dose, with 5 of 6 subjects achieving >98% drug-target engagement. Although AVL-292 plasma levels declined substantially by 8 hours, Btk engagement persisted throughout 24 hours, demonstrating that covalent inhibition of Btk with AVL-292 enables prolonged duration of activity without high levels of circulating drug. These results suggest that a once daily dosing schedule is sufficient for sustained Btk inhibition. Furthermore, the Btk protein level in circulating B lymphocytes from all study subjects was evaluated and the mean level was found to be 417.7 pg Btk/mg total protein. Interestingly, this finding in normal B cells correlates well with preclinical ex vivo analysis of Btk protein in primary CLL cells where comparable Btk protein levels were found. This suggests that the AVL-292 dose range and schedule identified for complete Btk engagement in this healthy volunteer trial is likely to inform appropriate dose selection in the subsequent phase 1b oncology study, allowing more rapid identification of a safe and clinically effective dose. Disclosures: Evans: Avila Therapeutics: Employment, Equity Ownership. Tester:Avila Therapeutics: Employment, Equity Ownership. Aslanian:Avila Therapeutics: Employment, Equity Ownership. Chaturvedi:Avila Therapeutics: Employment, Equity Ownership. Mazdiyasni:Avila Therapeutics: Employment, Equity Ownership. Sheets:Avila Therapeutics: Employment, Equity Ownership. Nacht:Avila Therapeutics: Employment, Equity Ownership. Stiede:Avila Therapeutics: Employment, Equity Ownership. Witowski:Avila Therapeutics: Employment, Equity Ownership. Lounsbury:Avila Therapeutics: Employment, Equity Ownership. Petter:Avila Therapeutics: Employment, Equity Ownership. Singh:Avila Therapeutics: Employment, Equity Ownership. Westlin:Avila Therapeutics: Employment, Equity Ownership.
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Rieder, Mark J., David Williamson, Anna Sherwood, Ryan O. Emerson, Cindy Desmarais, Moon Chung, Harlan Robins, and Christopher S. Carlson. "Frequency Of Gene Usage and Copy Number Variation Within The Rearranged Immunoglobin Heavy-Chain Variable Locus Based On Immune Repertoire Sequencing." Blood 122, no. 21 (November 15, 2013): 3486. http://dx.doi.org/10.1182/blood.v122.21.3486.3486.
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Abstract The human adaptive immune system is composed of both B and T cells that undergo somatic recombination at specific loci to create rearrangements of Variable (V), Diversity (D) and Joining (J) gene segments. For the B-cell immunoglobin receptor heavy-chain (IGH), the CDR3 regions are defined by the VDJ gene segments and nucleotide insertions/deletions at these junctions that create the vast sequence diversity of the IGH repertoire. Characterizing the germline DNA in these regions is impeded by the high sequence similarity between gene segments, mutation and copy-number variation (i.e. large insertions/deletions). Currently, there is a fundamental lack of information about the baseline IGH immune repertoire V gene usage and diversity within healthy human controls. To provide an estimate of this, we sequenced functionally recombined gene segments to infer the underlying gene structure. From a set of 132 healthy controls we sorted C19+/CD27+ B-cells from whole blood and amplified genomic DNA using a highly multiplexed PCR assay that targeted the rearranged IGH receptor locus. Following DNA sequencing and data processing to assign V, D and J gene families and names, we examined the usage frequency of IGHV gene segments across all individuals. We found that of the 98 V gene segments only 56 (57%) were used at a frequency > 0.1%, and ∼10 showed little to no usage (present in<1% of individuals). This data also allowed us to identify two IGHV genes currently annotated as orphons (pseudogenes assigned to an alternate chromosomal location) that had unambiguous functional usage (IGHV4/OR15-8; IGHV3/OR16-09) and therefore must reside at the IGH locus on chromosome 14. Finally, by taking this functional approach we were able to screen all V gene segments for germline copy-number variation (e.g. large insertion/deletion events encompassing individual genes) by looking for an excess of deletion events or modal changes in gene usage. We confirmed that existence of 12 of 15 previously identified deleted IGHV gene segments. Strong deletion evidence was observed for an additional six IGHV genes (IGHV3-NL1, IGHV3-33, IGHV1-24, IGHV4-04, IGHV3-41, IGHV3-35) and ten with highly likely germline deletion events. These data suggest that functional immune profiling of rearranged immune receptors provides a more robust method of identifying individual structural variation and provides insight into the immune repertoire of healthy controls. Disclosures: Rieder: Adaptive Biotechnologies: Employment, Equity Ownership. Williamson:Adaptive Biotechnologies: Employment, Equity Ownership. Sherwood:Adaptive Biotechnologies: Employment, Equity Ownership. Emerson:Adaptive Biotechnologies: Employment, Equity Ownership. Desmarais:Adaptive Biotechnologies: Employment, Equity Ownership. Chung:Adaptive Biotechnologies: Employment, Equity Ownership. Robins:Adaptive Biotechnologies: Consultancy, Equity Ownership, Patents & Royalties. Carlson:Adaptive Biotechnologies: Consultancy, Equity Ownership, Patents & Royalties.