Summary: A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available.

Top Publications

  1. Ashley E, Dhorda M, Fairhurst R, Amaratunga C, Lim P, Suon S, et al. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2014;371:411-23 pubmed publisher
    ..Funded by the U.K. Department of International Development and others; number, NCT01350856.). ..
  2. Audrey S, Procter S, Cooper A. The contribution of walking to work to adult physical activity levels: a cross sectional study. Int J Behav Nutr Phys Act. 2014;11:37 pubmed publisher
    To objectively examine the contribution to adult physical activity levels of walking to work. Employees (n = 103; 36.3 ± 11.7 years) at 17 workplaces in south-west England, who lived within 2 miles (3...
  3. Little P, Moore M, Kelly J, Williamson I, Leydon G, McDermott L, et al. Delayed antibiotic prescribing strategies for respiratory tract infections in primary care: pragmatic, factorial, randomised controlled trial. BMJ. 2014;348:g1606 pubmed publisher
    ..To estimate the effectiveness of different strategies involving delayed antibiotic prescription for acute respiratory tract infections...
  4. Feld J, Kowdley K, Coakley E, Sigal S, Nelson D, Crawford D, et al. Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin. N Engl J Med. 2014;370:1594-603 pubmed publisher
    ..In this phase 3 trial, we evaluated this regimen in previously untreated patients with HCV genotype 1 infection and no cirrhosis...
  5. Ferenci P, Bernstein D, Lalezari J, Cohen D, Luo Y, Cooper C, et al. ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV. N Engl J Med. 2014;370:1983-92 pubmed publisher
    ..We conducted two phase 3 trials to examine the efficacy and safety of this regimen in previously untreated patients with HCV genotype 1 infection and no cirrhosis...
  6. Gregg E, Li Y, Wang J, Burrows N, Ali M, Rolka D, et al. Changes in diabetes-related complications in the United States, 1990-2010. N Engl J Med. 2014;370:1514-23 pubmed publisher
    ..Funded by the Centers for Disease Control and Prevention.). ..
  7. Paton N, Kityo C, Hoppe A, Reid A, Kambugu A, Lugemwa A, et al. Assessment of second-line antiretroviral regimens for HIV therapy in Africa. N Engl J Med. 2014;371:234-47 pubmed publisher
    ..Removing the NRTIs or replacing them with raltegravir may provide a benefit...
  8. Huhn M, Tardy M, Spineli L, Kissling W, Forstl H, Pitschel Walz G, et al. Efficacy of pharmacotherapy and psychotherapy for adult psychiatric disorders: a systematic overview of meta-analyses. JAMA Psychiatry. 2014;71:706-15 pubmed publisher
    ..Because patients often benefit from both forms of therapy, research should also focus on how both modalities can be best combined to maximize synergy rather than debate the use of one treatment over the other. ..
  9. Marini S, Buonanno G, Stabile L, Ficco G. Short-term effects of electronic and tobacco cigarettes on exhaled nitric oxide. Toxicol Appl Pharmacol. 2014;278:9-15 pubmed publisher

More Information


  1. Magill S, Edwards J, Bamberg W, Beldavs Z, Dumyati G, Kainer M, et al. Multistate point-prevalence survey of health care-associated infections. N Engl J Med. 2014;370:1198-208 pubmed publisher
    ..We conducted a prevalence survey in 10 geographically diverse states to determine the prevalence of health care-associated infections in acute care hospitals and generate updated estimates of the national burden of such infections...
  2. Raemaekers J, André M, Federico M, Girinsky T, Oumedaly R, Brusamolino E, et al. Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: Clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol. 2014;32:1188-94 pubmed publisher
  3. Lee M, Ye C, Villani A, Raj T, Li W, Eisenhaure T, et al. Common genetic variants modulate pathogen-sensing responses in human dendritic cells. Science. 2014;343:1246980 pubmed publisher
    ..Our results reveal common alleles that explain interindividual variation in pathogen sensing and provide functional annotation for genetic variants that alter susceptibility to inflammatory diseases. ..
  4. Esper S, Levy J, Waters J, Welsby I. Extracorporeal membrane oxygenation in the adult: a review of anticoagulation monitoring and transfusion. Anesth Analg. 2014;118:731-43 pubmed publisher
    ..Furthermore, we review the different strategies for anticoagulation and treatment of coagulopathy while on ECMO. Finally, we discuss the cost of ECMO and associated blood product transfusion. ..
  5. Fairfax B, Humburg P, Makino S, Naranbhai V, Wong D, Lau E, et al. Innate immune activity conditions the effect of regulatory variants upon monocyte gene expression. Science. 2014;343:1246949 pubmed publisher
    ..Thus, applying pathophysiologically relevant immune stimuli assists resolution of functional genetic variants. ..
  6. Scarfone G, Bergamini A, Noli S, Villa A, Cipriani S, Taccagni G, et al. Characteristics of clear cell ovarian cancer arising from endometriosis: a two center cohort study. Gynecol Oncol. 2014;133:480-4 pubmed publisher
    ..We have investigated clinical and histological features of the largest published series of clear cell ovarian cancers arising in endometriosis using a retrospective database...
  7. Gerfaud Valentin M, Jamilloux Y, Iwaz J, Seve P. Adult-onset Still's disease. Autoimmun Rev. 2014;13:708-22 pubmed publisher
    First described in 1971, adult-onset Still's disease (AOSD) is a rare multisystemic disorder considered as a complex (multigenic) autoinflammatory syndrome...
  8. Braun S, Jessberger S. Adult neurogenesis: mechanisms and functional significance. Development. 2014;141:1983-6 pubmed publisher
    New neurons are generated throughout life in distinct regions of the mammalian brain. This process, called adult neurogenesis, has been implicated in physiological brain function, and failing or altered neurogenesis has been associated ..
  9. Lee E, Fleischmann R, Hall S, Wilkinson B, Bradley J, Gruben D, et al. Tofacitinib versus methotrexate in rheumatoid arthritis. N Engl J Med. 2014;370:2377-86 pubmed publisher
    ..The benefits of tofacitinib need to be considered in the context of the risks of adverse events. (Funded by Pfizer; ORAL Start number, NCT01039688.). ..
  10. Jacobson I, Dore G, Foster G, Fried M, Radu M, Rafalsky V, et al. Simeprevir with pegylated interferon alfa 2a plus ribavirin in treatment-naive patients with chronic hepatitis C virus genotype 1 infection (QUEST-1): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet. 2014;384:403-13 pubmed publisher
    ..The efficacy and safety of the combination of simeprevir, a one pill, once-daily, oral HCV NS3/4A protease inhibitor, plus peginterferon alfa 2a plus ribavirin were assessed in treatment-naive patients with HCV genotype 1 infection...
  11. Peters S, Huxley R, Woodward M. Diabetes as a risk factor for stroke in women compared with men: a systematic review and meta-analysis of 64 cohorts, including 775,385 individuals and 12,539 strokes. Lancet. 2014;383:1973-80 pubmed publisher
    ..These data add to the existing evidence that men and women experience diabetes-related diseases differently and suggest the need for further work to clarify the biological, behavioural, or social mechanisms involved. None. ..
  12. Price A, Kayange M, Zaba B, Chimbwandira F, Jahn A, Chirwa Z, et al. Uptake of prevention of mother-to-child-transmission using Option B+ in northern rural Malawi: a retrospective cohort study. Sex Transm Infect. 2014;90:309-14 pubmed publisher
    ..However, nearly half of eligible pregnant women not on ART at the start of ANC had not taken up the invitation to initiate (lifelong) ART by the time of delivery, leaving their infants potentially HIV-exposed. ..
  13. Antonakakis N, Collins A. The impact of fiscal austerity on suicide: on the empirics of a modern Greek tragedy. Soc Sci Med. 2014;112:39-50 pubmed publisher
    ..These empirical regularities potentially offer some guidance on the demographic targeting of suicide prevention measures and the case for 'economic' migration. ..
  14. Mereckiene J, Cotter S, Nicoll A, Lopalco P, Noori T, Weber J, et al. Seasonal influenza immunisation in Europe. Overview of recommendations and vaccination coverage for three seasons: pre-pandemic (2008/09), pandemic (2009/10) and post-pandemic (2010/11). Euro Surveill. 2014;19:20780 pubmed
    ..Coverage among healthcare workers remained low. ..
  15. Criner G, Connett J, Aaron S, Albert R, Bailey W, Casaburi R, et al. Simvastatin for the prevention of exacerbations in moderate-to-severe COPD. N Engl J Med. 2014;370:2201-10 pubmed publisher
    ..with diabetes or cardiovascular disease and those who were taking statins or who required statins on the basis of Adult Treatment Panel III criteria were excluded. Participants were treated from 12 to 36 months at 45 centers...
  16. Kaufman A, Zhou X, Reynolds M, Kaufman N, Green G, Weiss L. The possible societal impact of the decrease in U.S. blood lead levels on adult IQ. Environ Res. 2014;132:413-20 pubmed publisher
    ..The objectives of this study were to determine whether mean IQs of American adults, adjusted for demographics, have increased in concert with society's decreasing BLL...
  17. Fisher R, Acevedo C, Arzimanoglou A, Bogacz A, Cross J, Elger C, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014;55:475-82 pubmed publisher
    ..This revised definition of epilepsy brings the term in concordance with common use. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here. ..
  18. Rapsomaniki E, Timmis A, George J, Pujades Rodriguez M, Shah A, Denaxas S, et al. Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1·25 million people. Lancet. 2014;383:1899-911 pubmed publisher
    ..These findings emphasise the need for new blood pressure-lowering strategies, and will help to inform the design of randomised trials to assess them. Medical Research Council, National Institute for Health Research, and Wellcome Trust. ..
  19. Depondt C, Donatello S, Simonis N, Rai M, Van Heurck R, Abramowicz M, et al. Autosomal recessive cerebellar ataxia of adult onset due to STUB1 mutations. Neurology. 2014;82:1749-50 pubmed publisher
    ..Friedreich ataxia accounts for one-third of the cases in Caucasians; the others are due to a growing list of very rare molecular defects, including mild forms of metabolic diseases. In nearly 50%, the genetic cause remains undetermined. ..
  20. Pan C, Lin Y. Overweight, obesity, and age-related cataract: a meta-analysis. Optom Vis Sci. 2014;91:478-83 pubmed publisher
    ..To examine the longitudinal association of overweight/obesity with age-related cataract...
  21. Kumarswamy R, Bauters C, Volkmann I, Maury F, Fetisch J, Holzmann A, et al. Circulating long noncoding RNA, LIPCAR, predicts survival in patients with heart failure. Circ Res. 2014;114:1569-75 pubmed publisher
    ..LIPCAR is a novel biomarker of cardiac remodeling and predicts future death in patients with heart failure. ..
  22. Smith C, Ryom L, Weber R, Morlat P, Pradier C, Reiss P, et al. Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration. Lancet. 2014;384:241-8 pubmed publisher
    ..Consequently, the relative importance of other traditionally non-AIDS-related morbidities has increased. We investigated trends over time in all-cause mortality and for specific causes of death in people with HIV from 1999 to 2011...
  23. Antoniou A, Casadei S, Heikkinen T, Barrowdale D, Pylkäs K, Roberts J, et al. Breast-cancer risk in families with mutations in PALB2. N Engl J Med. 2014;371:497-506 pubmed publisher
    ..Germline loss-of-function mutations in PALB2 are known to confer a predisposition to breast cancer. However, the lifetime risk of breast cancer that is conferred by such mutations remains unknown...
  24. Gerfaud Valentin M, Maucort Boulch D, Hot A, Iwaz J, Ninet J, Durieu I, et al. Adult-onset still disease: manifestations, treatment, outcome, and prognostic factors in 57 patients. Medicine (Baltimore). 2014;93:91-9 pubmed publisher
    We conducted a retrospective observational study to describe a cohort and identify the prognostic factors in adult-onset Still disease (AOSD)...
  25. Martire L, Franks M. The role of social networks in adult health: introduction to the special issue. Health Psychol. 2014;33:501-4 pubmed publisher
    ..The goal of this special issue is to highlight recent research examining the role of social networks in adults' physical health. ..
  26. Kim M, Pinto S, Getnet D, Nirujogi R, Manda S, Chaerkady R, et al. A draft map of the human proteome. Nature. 2014;509:575-81 pubmed publisher
    ..In-depth proteomic profiling of 30 histologically normal human samples, including 17 adult tissues, 7 fetal tissues and 6 purified primary haematopoietic cells, resulted in identification of proteins ..
  27. Jokubaitis V, Li V, Kalincik T, Izquierdo G, Hodgkinson S, Alroughani R, et al. Fingolimod after natalizumab and the risk of short-term relapse. Neurology. 2014;82:1204-11 pubmed publisher
    ..This study provides Class IV evidence that RRs are not higher in patients with multiple sclerosis switching to fingolimod from natalizumab compared to those patients switching to fingolimod from other therapies. ..
  28. van Strien M, Sluijs J, Reynolds B, Steindler D, Aronica E, Hol E. Isolation of neural progenitor cells from the human adult subventricular zone based on expression of the cell surface marker CD271. Stem Cells Transl Med. 2014;3:470-80 pubmed publisher (SVZ) hold promise for future therapy for neurodegenerative disorders, because the stimulation of adult neurogenesis could potentially restore the function of degenerating neurons and glia...
  29. Yamada M, Johannesson B, Sagi I, Burnett L, Kort D, Prosser R, et al. Human oocytes reprogram adult somatic nuclei of a type 1 diabetic to diploid pluripotent stem cells. Nature. 2014;510:533-6 pubmed publisher
    ..Because of the therapeutic potential of diploid embryonic stem-cell lines derived from adult cells of diseased human subjects, we have systematically investigated the parameters affecting efficiency of ..
  30. Barrett E, Sathyanarayana S, Janssen S, Redmon J, Nguyen R, Kobrosly R, et al. Environmental health attitudes and behaviors: findings from a large pregnancy cohort study. Eur J Obstet Gynecol Reprod Biol. 2014;176:119-25 pubmed publisher
    ..Overcoming a lack of concern about environmental chemicals, particularly among certain sociodemographic groups, is important for the success of clinical or public health prevention measures. ..
  31. Wang J, Ning X, Yang L, Tu J, Gu H, Zhan C, et al. Sex differences in trends of incidence and mortality of first-ever stroke in rural Tianjin, China, from 1992 to 2012. Stroke. 2014;45:1626-31 pubmed publisher
    ..These results suggest that stroke will become one of the major diseases affecting women in future decades in China. ..
  32. Kashanian M, Hassan M, Roohi M, Yousefi H. Maternal outcomes of intimate partner violence during pregnancy: study in Iran. Public Health. 2014;128:410-5 pubmed publisher
  33. Hershman D, Lacchetti C, Dworkin R, Lavoie Smith E, Bleeker J, Cavaletti G, et al. Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2014;32:1941-67 pubmed publisher
    To provide evidence-based guidance on the optimum prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathies (CIPN) in adult cancer survivors.
  34. Githuka G, Hladik W, Mwalili S, Cherutich P, Muthui M, Gitonga J, et al. Populations at increased risk for HIV infection in Kenya: results from a national population-based household survey, 2012. J Acquir Immune Defic Syndr. 2014;66 Suppl 1:S46-56 pubmed publisher
    ..These data should inform priorities for high-risk populations in the upcoming Kenyan strategic plan on HIV/AIDS. ..
  35. Pujade Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: The AURELIA open-label randomized phase III trial. J Clin Oncol. 2014;32:1302-8 pubmed publisher
    ..Bevacizumab is active alone and in combination. AURELIA is the first randomized phase III trial to our knowledge combining bevacizumab with chemotherapy in platinum-resistant OC...
  36. Revello M, Lazzarotto T, Guerra B, Spinillo A, Ferrazzi E, Kustermann A, et al. A randomized trial of hyperimmune globulin to prevent congenital cytomegalovirus. N Engl J Med. 2014;370:1316-26 pubmed publisher
    ..In an uncontrolled study published in 2005, administration of CMV-specific hyperimmune globulin to pregnant women with primary CMV infection significantly reduced the rate of intrauterine transmission, from 40% to 16%...
  37. Gunderson C, Java J, Moore K, Walker J. The impact of obesity on surgical staging, complications, and survival with uterine cancer: a Gynecologic Oncology Group LAP2 ancillary data study. Gynecol Oncol. 2014;133:23-7 pubmed publisher
    ..To determine the association of body mass index (BMI) on complications, recurrence, and survival in GOG LAP2, a randomized comparison of laparoscopic versus open staging in clinically early stage uterine cancer (EC)...
  38. Xu J, Ou L. Resilience and quality of life among Wenchuan earthquake survivors: the mediating role of social support. Public Health. 2014;128:430-7 pubmed publisher
  39. Panter J, Costa S, Dalton A, Jones A, Ogilvie D. Development of methods to objectively identify time spent using active and motorised modes of travel to work: how do self-reported measures compare?. Int J Behav Nutr Phys Act. 2014;11:116 pubmed publisher
  40. Gordon S, Bruce N, Grigg J, Hibberd P, Kurmi O, Lam K, et al. Respiratory risks from household air pollution in low and middle income countries. Lancet Respir Med. 2014;2:823-60 pubmed publisher
    ..To make clean energy available to all people is the long-term goal, with an intermediate solution being to make available energy that is clean enough to have a health impact. ..
  41. Gianni L, Eiermann W, Semiglazov V, Lluch A, Tjulandin S, Zambetti M, et al. Neoadjuvant and adjuvant trastuzumab in patients with HER2-positive locally advanced breast cancer (NOAH): follow-up of a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet Oncol. 2014;15:640-7 pubmed publisher
  42. MacPherson P, Lalloo D, Webb E, Maheswaran H, Choko A, Makombe S, et al. Effect of optional home initiation of HIV care following HIV self-testing on antiretroviral therapy initiation among adults in Malawi: a randomized clinical trial. JAMA. 2014;312:372-9 pubmed publisher
    ..Self-testing for HIV infection may contribute to early diagnosis of HIV, but without necessarily increasing antiretroviral therapy (ART) initiation...
  43. CAMPBELL F, Conti G, Heckman J, Moon S, Pinto R, PUNGELLO E, et al. Early childhood investments substantially boost adult health. Science. 2014;343:1478-85 pubmed publisher
    ..Much less is known about their benefits for adult health...
  44. Fiskesund R, Steen J, Amara K, Murray F, Szwajda A, Liu A, et al. Naturally occurring human phosphorylcholine antibodies are predominantly products of affinity-matured B cells in the adult. J Immunol. 2014;192:4551-9 pubmed publisher
    ..These results provide novel insights into the cellular and molecular ontogeny of atheroprotective PC Abs, thereby offering new opportunities for Ab-based therapeutic interventions. ..
  45. King T, Bradford W, Castro Bernardini S, Fagan E, Glaspole I, Glassberg M, et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014;370:2083-92 pubmed publisher
    ..We sought to confirm the beneficial effect of pirfenidone on disease progression in such patients...
  46. Grinsztejn B, Hosseinipour M, Ribaudo H, Swindells S, Eron J, Chen Y, et al. Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial. Lancet Infect Dis. 2014;14:281-90 pubmed publisher
    ..We reported previously that early antiretroviral treatment reduced HIV-1 transmission by 96%. We aimed to compare the effects of early and delayed initiation of antiretroviral treatment on clinical outcomes...
  47. Georgantas R, Streicher K, Greenberg S, Greenlees L, Zhu W, Brohawn P, et al. Inhibition of myogenic microRNAs 1, 133, and 206 by inflammatory cytokines links inflammation and muscle degeneration in adult inflammatory myopathies. Arthritis Rheumatol. 2014;66:1022-33 pubmed publisher
    ..The purpose of this study was to identify possible new targets for drug development by exploring the mechanism by which inflammation may play a role in the pathology of the inflammatory myopathies...
  48. KROP I, Kim S, Gonzalez Martin A, LoRusso P, Ferrero J, Smitt M, et al. Trastuzumab emtansine versus treatment of physician's choice for pretreated HER2-positive advanced breast cancer (TH3RESA): a randomised, open-label, phase 3 trial. Lancet Oncol. 2014;15:689-99 pubmed publisher
    ..We aimed to compare trastuzumab emtansine, an antibody-drug conjugate comprising the cytotoxic agent DM1 linked to trastuzumab, with treatment of physician's choice in this population of patients...
  49. Zhang F, Zhao X, Ji X, Han R, Li P, Du M. Diagnostic value of acoustic radiation force impulse imaging for assessing superficial lymph nodes: A diagnostic accuracy study. Medicine (Baltimore). 2017;96:e8125 pubmed publisher
    ..ARFI imaging may be a feasible method for differentiating MLNs from CLNs...
  50. Sun Y, Liao M, He L, Zhu C. Comparison of breast-conserving surgery with mastectomy in locally advanced breast cancer after good response to neoadjuvant chemotherapy: A PRISMA-compliant systematic review and meta-analysis. Medicine (Baltimore). 2017;96:e8367 pubmed publisher
    ..The objective in this study is to analyze the safety of BCS in the management of LABC in patients with good response to NACT...
  51. Tayal U, Newsome S, Buchan R, Whiffin N, Halliday B, Lota A, et al. Phenotype and Clinical Outcomes of Titin Cardiomyopathy. J Am Coll Cardiol. 2017;70:2264-2274 pubmed publisher
  52. Murakami K, Ohkubo T, Hashimoto H. Distinct association between educational attainment and overweight/obesity in unmarried and married women: evidence from a population-based study in Japan. BMC Public Health. 2017;17:903 pubmed publisher
    ..These findings indicate that the social influences bound to educational background affect women's overweight/obesity. ..
  53. Horn J, Damm O, Greiner W, Hengel H, Kretzschmar M, Siedler A, et al. Influence of demographic changes on the impact of vaccination against varicella and herpes zoster in Germany - a mathematical modelling study. BMC Med. 2018;16:3 pubmed publisher
  54. Gonzaga L, Vanderlei L, Gomes R, Valenti V. Caffeine affects autonomic control of heart rate and blood pressure recovery after aerobic exercise in young adults: a crossover study. Sci Rep. 2017;7:14091 pubmed publisher
    ..Caffeine was shown to be capable of delaying parasympathetic recovery but did not influence the behavior of the respiratory rate, oxygen saturation or frequency-domain HRV indices. ..
  55. Luymes C, Poortvliet R, van Geloven N, de Waal M, Drewes Y, Blom J, et al. Deprescribing preventive cardiovascular medication in patients with predicted low cardiovascular disease risk in general practice - the ECSTATIC study: a cluster randomised non-inferiority trial. BMC Med. 2018;16:5 pubmed publisher
    ..An attempt to deprescribe medication can be considered, taking patient preferences into consideration. This study was registered with Dutch trial register on 20 June 2012 ( NTR3493 ). ..
  56. Pearson H, Fleming T, Chhoun P, Tuot S, Brody C, Yi S. Prevalence of and factors associated with utilization of herbal medicines among outpatients in primary health centers in Cambodia. BMC Complement Altern Med. 2018;18:114 pubmed publisher
    ..Understanding TCAM use in the general population will support health care practitioners and policy makers to make informed decisions about the use of TCAM. Integration of TCAM into the primary health system should be further explored. ..