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我们会通过消息、邮箱等方式尽快将举报结果通知您。The epidemiologic profile and prevalence of cardiopathy in Trypanosoma cruzi infected blood donor candidates, Londrina, Paran&, Brazil (PDF Download Available)
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27.14Universidade Estadual de Londrina37.49Universidade Estadual de LondrinaAbstractTo describe the epidemiologic profile and prevalence of cardiopathy in 163 Trypanosoma cruzi serum positive blood donor candidates, a descriptive study was carried out between August, 1996 and November, 1997 at the Londrina State University Chagas Disease Outpatient Clinic. The profile found was: young, average age 42.95 +/- 8.62 male (65%); Caucasian (84%); lo agricultural worker (26%); born in the state of Paraná (67%); from rural areas (85%); migrated to the city (85%); and the vector as the main mechanism of transmission. During the clinical characterization a chronic cardiac form was found in 38% of the patients and classified as cardiac suggestive form in 21% and little suggestive of Chagas disease in 17%. No significant difference was found among age group distribution, sex and the presence of cardiac symptoms in patients with or without cardiopathy. This study emphasizes the importance of expanding medical services to areas with a greater prevalence of infected individuals, in a hierarchical manner and aiming at decentralization.Hide publication data in PortuguesePerfil epidemiológico e prevalência de cardiopatia em candidatos a doador de sangue infectados por Trypanosoma cruzi, Londrina, Paraná, BrasilAbstractObjetivando-se tra?ar o perfil epidemiológico e a prevalência de cardiopatia, realizou-se estudo descritivo em 163 candidatos a doador de sangue infectados por Trypanosoma cruzi, atendidos no período de agosto de 1996 a novembro de 1997 no ambulatório de doen?a de Chagas do Hospital de Clínicas da Universidade Estadual de Londrina. O perfil epidemiológico foi de paciente jovem, média de idade de 42,95 ± 8,62 anos, sexo masculino (65%), ra?a branca (84%), baixa escolaridade, baixa renda familiar, agricultor (26%), natural do estado do Paraná (67%), de zona rural (85%), residindo atualmente em zona urbana (85%), sendo o vetorial o principal mecanismo de transmiss?o. A forma cr?nica cardíaca, encontrada em 38% foi classificada em forma cardíaca sugestiva de doen?a de Chagas em 21% e pouco sugestiva em 17% dos pacientes. N?o houve diferen?a significativa na distribui??o da faixa etária, sexo e presen?a de sintomas cardíacos em rela??o aos pacientes com ou sem cardiopatia. O estudo ressalta a import?ncia da expans?o de servi?os de atendimento em regi?es de maior ocorrência de indivíduos infectados e manuten??o de servi?os de referência, para oferecer atendimento de forma descentralizada e hierarquizada.Discover the world's research14+ million members100+ million publications700k+ research projectsFigures
Rev. Inst. Med. trop. S. Paulo47(6):321-326, November-December, 2005(1) Disciplina de Cardiologia do Depto. de Clínica Médica da Universidade Estadual de Londrina (UEL), Londrina, PR, Brasil.(2) Disciplina de Moléstias Infecciosas do Depto. de Clínica Médica da UEL, Londrina, PR, Brasil.(3) Disciplina de Matemática Aplicada do Depto. de Matemática da UEL, Londrina, PR, Brasil.(4) Disciplina de Cirurgia Cardíaca do Depto. de Cirurgia da UEL, Londrina, PR, BrasilCorrespondence to: Divina Seila de Oliveira-Marques, Hospital Universitário Regional do Norte do Paraná, R. Robert Koch 60,
Londrina, PR, Brasil. e-mail: d.seila@cardiol.brTHE EPIDEMIOLOGIC PROFILE AND PREVALENCE OF CARDIOPATHY IN Trypanosoma cruziINFECTED BLOOD DONOR CANDIDATES, LONDRINA, PARAN?, BRAZILDivina Seila de OLIVEIRA-MARQUES(1), Ana Maria BONAMETTI(2), Tiemi MATSUO(3) & Francisco GREGORI JUNIOR(4)SUMMARYTo describe the epidemiologic profile and prevalence of cardiopathy in 163 Trypanosoma cruzi serum positive blood donorcandidates, a descriptive study was carried out between August, 1996 and November, 1997 at the Londrina State UniversityChagas Disease Outpatient Clinic. The profile found was: young, average age 42.95 ± 8.62 male (65%); Caucasian (84%);low le agricultural worker (26%); born in the state of Paraná (67%); from rural areas (85%);migrated to the city (85%); and the vector as the main mechanism of transmission. During the clinical characterization a chroniccardiac form was found in 38% of the patients and classified as cardiac suggestive form in 21% and little suggestive of Chagasdisease in 17%. No significant difference was found among age group distribution, sex and the presence of cardiac symptoms inpatients with or without cardiopathy. This study emphasizes the importance of expanding medical services to areas with a greaterprevalence of infected individuals, in a hierarchical manner and aiming at decentralization.KEYWORDS: Chagas D American T E Myocardiopathy.INTRODUCTIONChagas disease is a parasitosis caused by the protozoanTrypanosoma cruzi. It is endemic in the Americas, from central Mexicoto the south of Argentina and Chile12,34. It is estimated that the numberof infected individuals in Brazil is around three million and it is one ofthe greatest public health problems in the Country1,13.Means to control the main route of transmission - vectorial - havebeen available since the 40s, following the proven effectiveness oftreatment with insecticides to eliminate the vector in a direct way orindirectly through improvement of living conditions in rural areas34.Prior selection of blood donors through serologic screening is the mainstrategy to prevent transfusion transmission - the second most importantpath of transmission - which was introduced as a health policy in Brazilin 19692. However, with the emergence of acquired immunodeficiencyvirus infections, a complete review of the policy for blood andhemoderivates was carried out in Brazil. The Ministry of Healthrecommended that blood from all donors should be tested for anti-Trypanosoma cruzi antibodies using at least two serologic techniques2,36.With these measures, control by the hemotherapy services has beenelevated to over 80% throughout Brazil and the median of infecteddonor candidates is below 0.8%14. In Paraná, the effectiveness of thesemeasures was demonstrated from 1985, when an analysis of 1,977blood donor candidates from 33 cities of the state showed aseropositivity of 7.2%29. Furthermore, according to the Coordinationof Blood and Hemoderivates of the Ministry of Health this figure forthe state as whole had decreased to 0.86% in 19956. In the city ofLondrina, data collection carried out by various authors in the years of, 1996 and 1998, found a decreasing seroprevalence of6.92%, 7.49%, 1.4% and 1.3%, respectively4,5,31,32.Nowadays, with the main way of transmission under control, theprincipal concern is regarding assistance to infected individuals,particularly their situation in the job market, the social servicesinvolved and the necessity for adequate medical care18. The assistanceto rejected donors referred by hemotherapy
services is a specialconcern. These donors present peculiarities such as the presence ofinconclusive serologic screening, or a confirmed diagnosis inapparently healthy individuals, that might or might not have clinicalimplications - of which cardiopathy is the most frequent15,16,19. It isnot the responsibility of hemotherapy services to clinically attend therefore there is a need to provide related care servicesin various centers23.Faced with a previous study that affirmed that 80% of infectedpatients could receive medical care in primary care services18, a clinicalepidemiologic study in a sample of our population was proposed. Theaim of this study was to set goals for the improvement of such services
322OLIVEIRA-MARQUES, D.S.; BONAMETTI, A.M.; MATSUO, T. & GREGORI JUNIOR, F. - The epidemiologic profile and prevalence of cardiopathy in Trypanosoma cruzi infected blooddonor candidates, Londrina, Paraná, Brazil. Rev. Inst. Med. trop. S. Paulo, 47(6):321-326, 2005.and to assess the possibility of decentralization, through determinationof the patients‘ characteristics.MATERIAL AND METHODSDesign: A descriptive study carried out through the review ofmedical records and dossiers of 163 blood donor candidates thatpresented positive serologic reaction to Trypanosoma cruzi, referredby hemotherapy services and attended at the Londrina State UniversityChagas Disease Outpatient Clinic from August 1996 to November 1997.Data collection and mensurationPersonal data: Hospital record, age, gender, race, educational level,monthly family income, profession, origin and present residency,classified by state of origin. The State of Paraná was divided intogeographic micro and meso regions, according to the Brazilian Instituteof Geography and Statistics20.Epidemiologic data: The way of infection transmission wasevaluated by knowledge of the vector, residency or travel in endemicareas, mother or other family member with Chagas disease and historyof blood transfusion. The patients were also asked whether they hadeffectively donated blood prior to the present diagnosis of T. cruziinfection. Serologic diagnosis: Carried out through indirectimmunofluorescence techniques9 (LIOSERUM, S?o Paulo, Brazil andLABORCLIN, Paraná, Brazil); indirect hemagglutination21,26 (EBRAM,S?o Paulo, Brazil) and immunoenzymatic assay35 (ABBOTT, S?o Paulo,Brazil). The individuals that presented at least two positive reactionswere considered infected.Clinical data: Patients that complained of at least one of thefollowing were considered symptomatic: dyspnea, palpitations,precordialgia, fainting and/or dizziness. All patients were submittedto conventional electrocardiogram in 12 derivations with long D2 (EKG)and thorax radiography at posteroanterior incidence. EKG withalterations characteristic of Chagas disease were considered to be thosethat revealed the presence of: complete right bundle branch block, leftanterior hemiblock, A-V block, multifocal ventricular extrasystolesand sinusal bradycardia connected to ventricular repolarizationalteration or to other alterations, according to the method used by theNational Electrocardiographic Survey on Chagas Disease24. To evaluatethe presence of cardiomegaly, analysis of the cardiothoracic index(I:CT) was used in thorax radiography, considered indicator ofcardiomegaly when greater than 50%. The cardiac form was definedby the presence of electrocardiographic alterations and/or cardiomegalyin the thorax radiography. The cardiac form was classified as suggestiveof Chagas disease when characteristic electrocardiographic alterationswere present, and little suggestive of Chagas disease when otherelectrocardiographic alterations were identified.Statistical analysis: The data was stored in the software Epi Inforelease 6.04 and analyzed with SAS software - Statistical AnalysisSystem release 6.11. In the analysis, descriptive statistics were usedand Chi-square test applied to compare proportions. Statisticalsignificance was set at the 5% level.RESULTSAge varied from 18 to 63 years, with a mean of 42.5 and standarddeviation of 8.62 years. It was observed that 46% of the patients werein the 40-50 y age group. Most of the patients were male - 106 (65%),white - 137 (84%), illiterate - 23 (14%) or with incomplete basiceducation - 109 (67%) and with monthly family income up to threeminimum wages - 134 (82%). Agriculture was the professional areamost referred to, followed by self-employed, identified in 42 (26%)and 31 (19%) patients, respectively. Most of the patients were born inthe state of Paraná - 108 (66%), followed by Minas Gerais - 23 (14%),S?o Paulo - 20 (12.5%) and other states - 12 (7.5%). It was observedthat 138 (85%) patients came from rural areas. In the evaluation of theorigin of 108 patients from the state of Paraná, 91 (84%) come fromthe North Pioneer mesoregion, mainly from the microregions ofWenceslay Braz - 41 (38%), Assaí - 22 (20%) and Cornélio Procópio -20 (18.5%). Only 6 (5.5%) come from the microregion of Londrina.All 163 patients currently reside in the state of Paraná, the majority inthe urban area - 138 (85%), proportionally distributed among the NorthPioneer - 82 (50.4%) and North Central - 80 (49%) mesoregions, withpredominance of the microregion of Londrina - 64 (39%), followed byWenceslay Braz - 44 (27%).Regarding the presence of symptoms, it was observed that 98 (60%)patients presented symptoms and 65 (40%) were asymptomatic. In theEKG analysis, 107 (65%) did not present alteration. Out of 56 (34.5%)patients with electrocardiographic alterations (Table 1), 29 (18%)presented alterations considered characteristic of Chagas disease and27 (16.5%) presented other alterations. It was observed that 145 (89%)patients presented normal cardiac area and 18 (11%) presentedcardiomegaly in the thorax radiography. Analysis of theTable 1Distribution of the electrocardiographic alterations in 56 of the163 patients studiedAlterations in electrocardiogram No. %VRA 17 30.0SB 8 14.0CRBB and LAH 8 14.0CRBB 6 11.0LAH 3 5.0VE 2 3.5CRBB, LAH and VRA 2 3.5SB and LAH 2 3.5LAH and VRA 2 3.51° AVB 1 2.02° AVB 1 2.01° AVB, LAH and VRA 1 2.02° AVB, LAH and CRBB 1 2.0SB and CRBB 1 2.0SB and VE 1 2.0TOTAL 56 100.0CRBB: complete right LAH: lef 1°AVB: 1st at 2° AVB: 2nd at SB: sinusal VE: ventricular
VRA: ventricular repolarizationalteration.
OLIVEIRA-MARQUES, D.S.; BONAMETTI, A.M.; MATSUO, T. & GREGORI JUNIOR, F. - The epidemiologic profile and prevalence of cardiopathy in Trypanosoma cruzi infected blooddonor candidates, Londrina, Paraná, Brazil. Rev. Inst. Med. trop. S. Paulo, 47(6):321-326, 2005.323electrocardiogram and thorax radiography for clinical characterizationshowed that 62 (38%) patients presented electrocardiographic and/orradiologic alterations, which characterized the presence of the cardiacform. Out of these, 35 (21%) were characterized as suggestive of cardiacform and 27 (16.5%) as cardiac form little suggestive of Chagas disease(Fig. 1).When comparing the clinical forms of Chagas disease accordingto age group, the chronic cardiac form was less frequent in individualsunder 30 years of age (2%), despite the fact that a proportionaldistribution of clinical forms in different age groups was observed (p= 0.210) (Fig. 2). It was also observed that, when comparing the clinicalform and gender, the chronic cardiac form was present in 19/57 (33%)female patients and in 43/106 (41%) male patients. The results werenot statistically significant (p = 0.364) (Fig. 3). When the clinical formof Chagas disease was compared to the presence of symptoms, it wasevident that in patients with chronic cardiac form, 45% presentedsymptoms and 55% presented no symptoms. In those patients withchronic non-cardiac form, 37% presented symptoms and 63% presentedno symptoms. When comparing these distributions, statisticalsignificance was not observed (p = 0.280) (Fig. 4).DISCUSSIONAbout one hundred years after its description, Chagas diseaseremains a serious public health problem. Its epidemiologic and clinicalaspects have been emphasized and continue to be of great value for theplanning of prophylactic actions - seen as a great weapon against thisinfection12.The epidemiologic profile of the blood donor candidate infectedby Trypanosoma cruzi revealed a young, male and white individualwith a low level of education. These results were similar to thosepublished by GONTIJO et al. (1996), with the exception of race, asFig. 1 - Distribution of the 163 studied patients, in accordance with the clinical form ofChagas disease.Fig. 2 - Percentage distribution of the patients according to age and clinical form of Chagasdisease.Fig. 3 - Percentage distribution of the patients according to gender and clinical form ofChagas disease.Fig. 4 - Percentage distribution of the patients according to the presence of symptoms andclinical form of Chagas disease.
324OLIVEIRA-MARQUES, D.S.; BONAMETTI, A.M.; MATSUO, T. & GREGORI JUNIOR, F. - The epidemiologic profile and prevalence of cardiopathy in Trypanosoma cruzi infected blooddonor candidates, Londrina, Paraná, Brazil. Rev. Inst. Med. trop. S. Paulo, 47(6):321-326, 2005.the author found a predominance of mulatto or black patients (60%).This difference may be explained by regional variations in racialdistribution. According to GUARIENTO et al. (1996), thepredominance of males is explained by cultural differences in thepractice of blood donation that attributes male individuals the role ofdonor par excellence.Other identified aspects were the prevalence of low monthly familyincome and agriculture as the professional area. Previous observationshad already revealed that the Chagas patient is generally an individualwith low professional qualification and incomplete education, whoworks in functions that require greater physical effort and that do notoffer adequate conditions of remuneration16.Regarding origin, the majority was born in the rural area (85%),coming from the state of Paraná - 108 (66%), followed by 23 (14%)from Minas Gerais, 23 (14%) from S?o Paulo and 12 (7.5%) fromother states. Of 108 patients from the state of Paraná, the majority(84%) came from the North Pioneer mesoregion. These characteristicsare related to aspects of colonization and development of the regionsconsidered endemic in the State, since, from the XIX Century on, thenorth region has differed from the other regions due to the developmentof coffee culture, started by migrants from the states of Minas Geraisand S?o Paulo7.The migrating component was evident in this study, especiallyregarding rural-urban migration, since, when the present home wasanalyzed, all patients lived in the state of Paraná and the majority (85%)in an urban area. These results are connected to the regional transformationsthat occurred within the state, mainly following changes in agriculturalproduction. From 1960 on, coffee plantations began to be replaced byother mechanized cultures such as soy and wheat, which led to migrationto cities that required a larger labor force due to the industrializationprocess8. This intense rural-urban migratory process was also observed instudies carried out with Chagas patients in other regions of the Countrysuch as the state of S?o Paulo and Minas Gerais3,17,18.Most of the patients (142/87%) evaluated in this study were fromregions endemic for Chagas disease and born in a rural area. This factsuggests that the predominant mechanism of transmission was vectorial.Out of the remaining 21 patients, 10 (6%) had a history of transfusionof blood or hemoderivates, characterizing the possibility of transfusiontransmission and 6 (4%) were children of mothers with positive serologyfor Chagas disease, a fact suggesting the possibility of congenitaltransmission. Five (3%) patients were born and always resident in anurban area and denied a previous history of blood transfusion or motherwith positive serology for Chagas disease, consequently it wasimpossible to characterize the transmission mechanism.From 163 patients, 39 (24%) reported having already donated blood,out of which 14 (34%) referred to negative result of previous serology.Some authors have already demonstrated the possibility of false negativeresults of serologic reactions to the diagnosis of Trypanosoma cruziinfection in proven infected individuals, mainly when techniques withlow sensitivity and specificity were used, such as the complementfixation reaction10.Electrocardiographic alterations were presented by 56/163 (34%)individuals although in only 29 (18%) patients the electrocardiographicwave detected alterations considered characteristic of Chagascardiopathy. According to MAC?DO (1993), in the NationalElectrocardiographic Survey to evaluate the prevalence of Chagascardiopathy, the prevalence of electrocardiographic alterations inindividuals seropositive for Trypanosoma cruzi infection was initiallyof 37.4%, but fell 24.4%, when only the alterations characteristic ofChagas cardiopathy were considered. In the state of Paraná, the samesurvey detected that 23% of the seropositive patients presentedelectrocardiographic alterations characteristics of Chagas cardiopathy.When the electrocardiographic and radiologic alterations areanalyzed as a whole, in 35 (21%) patients, the presence of characteristicelectrocardiographic alterations and/or the presence of cardiomegalyin the thorax radiography characterizing the cardiac form suggestiveof Chagas
in 27 (17%) patients, non-characteristic electrocardiographic alterations were observed,characterizing a cardiac form little suggestive of Chagas disease. Whenconsidering all the electrocardiographic and radiologic alterationsdetected, the prevalence of Chagas cardiopathy was 38% (62 patients).Studies carried out on samples of blood donor candidates seropositivefor Trypanosoma cruzi infection have detected prevalence of Chagascardiopathy between 30.0 and 56.7%10,18,22,27,33. This variation may berelated to a lack of standardization of the adapted criteria inelectrocardiographic analysis or to regional variations in the prevalenceof this infection.The analysis of the clinical form of patients evaluated in the presentstudy revealed that 65 (40%) the most frequentreported symptom was dyspnea in 45 (28%), followed by palpitationin 34 (21%), dizziness in 26 (16%), precordialgia in 24 (15%) andfainting in 6 (4%). When comparing the patients with Chagascardiopathy to those without this illness, regarding the presence ofsymptoms, it was verified that there was no statistically significantdifference between both groups. According to MARIN-NETO, SIM?ES& SARABANDA (1997), the natural history of Chagas disease isprodigal in phases and clinical forms and there is flagrant dissociationbetween the presence of symptoms and objective signs of organicdamage.The evaluation according to age showed that there was a greaterfrequency of cardiopathy in patients who were 40 years old and older,however, without statistical significance. According to PRATA et al.(1993), the greater frequency of electrocardiographic alterations in theelderly may be related to longer time evolution of the Chagascardiopathy and to the concomitance of other affections such as systolicarterial hypertension and coronary insufficiency. This difference wasprobably not detected statistically in our study due to the sample size.According to PEREIRA-BARRETTO et al. (1993), the prevalenceof Chagas cardiopathy is greater and the prognosis worse in malepatients seropositive for Trypanosoma cruzi infection. No differencewas found regarding the prevalence of cardiopathy and gender in ourstudy.In view of the present results and according to the principle thatattendance of Chagas patients should take place preferentially close towhere they live, we concluded that human resources training and
OLIVEIRA-MARQUES, D.S.; BONAMETTI, A.M.; MATSUO, T. & GREGORI JUNIOR, F. - The epidemiologic profile and prevalence of cardiopathy in Trypanosoma cruzi infected blooddonor candidates, Londrina, Paraná, Brazil. Rev. Inst. Med. trop. S. Paulo, 47(6):321-326, 2005.325qualification are necessary, along with the organization of serviceswith diagnostic support to provide good quality serology and basiccomplementary exams such as electrocardiogram and thoraxradiography. These should be provided in health services alreadyexistent in the regions with great occurrence of infected individualsrequiring assistance at primary level. Since interinstitutional integrationis a basic characteristic in the operationalization of the model of healthcare in Chagas disease, the maintenance of a Service at the LondrinaState University Clinics Hospital is necessary, to serve as a referencecenter for patients who need specialized care.RESUMOPerfil epidemiológico e prevalência de cardiopatia em candidatosa doador de sangue infectados por Trypanosoma cruzi, Londrina,Paraná, BrasilObjetivando-se tra?ar o perfil epidemiológico e a prevalência decardiopatia, realizou-se estudo descritivo em 163 candidatos a doadorde sangue infectados por Trypanosoma cruzi, atendidos no período deagosto de 1996 a novembro de 1997 no ambulatório de doen?a deChagas do Hospital de Clínicas da Universidade Estadual de Londrina.O perfil epidemiológico foi de paciente jovem, média de idade de 42,95± 8,62 anos, sexo masculino (65%), ra?a branca (84%), baixaescolaridade, baixa renda familiar, agricultor (26%), natural do estadodo Paraná (67%), de zona rural (85%), residindo atualmente em zonaurbana (85%), sendo o vetorial o principal mecanismo de transmiss?o.A forma cr?nica cardíaca, encontrada em 38% foi classificada em formacardíaca sugestiva de doen?a de Chagas em 21% e pouco sugestiva em17% dos pacientes. N?o houve diferen?a significativa na distribui??oda faixa etária, sexo e presen?a de sintomas cardíacos em rela??o aospacientes com ou sem cardiopatia. O estudo ressalta a import?ncia daexpans?o de servi?os de atendimento em regi?es de maior ocorrênciade indivíduos infectados e manuten??o de servi?os de referência, paraoferecer atendimento de forma descentralizada e hierarquizada.REFERENCES1. AKHAVAN, D. - Análise de custo-efetividade do programa de controle da doen?a deChagas no Brasil: relatório final. Brasília, OPAS, 2000.2. ANDRADE, A.L.; ZICKER, F. & MARTELLI, C.M. - An epidemiological approach tostudy congenital Chagas’ disease. Cad. Saúde públ. (Rio de J.), 10(supl. 2): 345-351, 1994.3. ANTUNES, C.M.; CHIARI, C.A. & MEYER, M.A. - Epidemiologia da doen?a de Chagasem Belo Horizonte, MG, Brasil. Rev. Soc. bras. Med. trop., 17(supl.): 69, 1984.4. 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ArticleFull-text availableMar 2007ArticleFull-text availableApr 2009ArticleFull-text availableApr 2009Show moreProjectArticleSeptember 2010ArticleSeptember 2008 · In this chapter it is emphasized the importance to guarantee safety and high quality blood transfusions. Besides, the following topics are analyzed: the importance of Trypanosoma cruzi infection acquired by blood transfusions, the obligatory screening implemented in Chilean blood banks and serological diagnostic techniques used that for, the seroprevalence observed, the importance to confirm... [Show full abstract]ArticleJanuary 1999 · Transmission of American trypanossomiasis by transfusion has been reduced by expansion of control measures of blood quality in Brazil. A research project was, therefore, undertaken to evaluate soropositivity for Trypanosoma cruzi infection on blood donors and to compare this rate with those found in 1958 and 1975 in blood banks.
A transversal study was carried out on blood donors in Londrina,... [Show full abstract]ArticleJune 2005 · ArticleJune 2005 · Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.This publication is from a journal that may support self archiving.Last Updated: 19 Dec 17