Petri Kulmala

• MD, PhD
• Professor at University of Oulu

Purpose This study aims to investigate final-year medical students’ perceptions regarding the significance of different managerial roles in fulfilling physician leaders’ work. Design/methodology/approach In 2020, an electronic questionnaire was distributed to all final-year medical students at the University of Oulu, Finland. A quantitative analys...

Purpose A unique aspect of the Finnish healthcare system is that medical students can assume formal doctoral positions under specific circumstances while still pursuing their medical studies. This study investigates the prevalence of such engagements and examines whether factors such as gender, age, or pre-medical school educational background infl...

Lääketieteen koulutuksen tutkimus muotoutui omaksi lääketieteen alakseen 1950-luvun lopulla. Samoin kuin muutakin tutkimusta, lääketieteen koulutuksen tutkimusta tehdään tieteellisen tutkimuksen periaatteiden mukaisesti hyödyntäen sekä määrällisiä että laadullisia tutkimusmenetelmiä. Tutkimuskohteena ovat lääkärikoulutukseen, lääkäriprofessioon ja...

Background Leadership competence is increasingly recognized as a critical priority for all physicians, but new graduates often feel only partially prepared for leadership roles. However, integrating more leadership education into the already saturated medical curriculum poses challenges regarding timing and implementation. This study explores this...

Digitaalisuus ja etälääketiede ovat lisääntyneet maailmanlaajuisesti. Tämä luo uusia osaamistarpeita digitaalisten ratkaisujen hyödyntämiseen potilaiden hoidossa. Osaamisvajeet voivat lisätä tehottomuutta, tietosuojan ja tietoturvan riskejä sekä vaarantaa potilasturvallisuuden. MEDigi-hankkeessa tunnistettiin digitaalisen lääketieteen osaamistarpee...

BACKGROUND Modern healthcare systems worldwide are facing challenges, and digitalization is viewed as a means to strengthen healthcare globally. As digitalization in healthcare demands adjustments in practices, policies, and workflows, assessing healthcare professionals' competencies is crucial for effective integration into their work environment....

This qualitative study investigated tomorrow’s physicians’ - medical students’ - perceptions of how physicians should be led and their interest in pursuing leadership positions as these issues have never been studied in Finland. In 2020, an online questionnaire was distributed to final-year medical students (n = 162, response rate 110/68%). Student...

Different electronic medical record systems (EMR) have established themselves as part of the Finnish health care service provision. There is a need to ensure health care professionals’ competence and training for such systems. The MEDigi project, aimed to modernize and harmonize the Finnish basic medical education, recognized EMR systems as a key c...

Lähtökohdat Lääkärijohtaminen kytkeytyy terveydenhuollon laatuun ja tehokkuuteen, mutta on jäänyt kliinikon työn varjoon. Erikoistuvien lääkärien ja hammaslääkärien valtakunnallinen johtamiskoulutus (EJO) on uudistumassa. Selvitimme Oulun yliopiston EJO-kurssille osallistuvien taustoja ja näkemyksiä lääkärijohtamisesta. Menetelmät Aineisto kerätti...

Background Every physician has a unique professional identity. However, little is known about the diversity of identities among physicians. This study aimed to quantitatively assess the professional identity of physicians in Finland using descriptions of professional identity. Methods This study was part of a larger cross-sectional Finnish Physici...

Prematurity has been linked to lower muscular fitness and increased morbidity across the human lifespan. Hand grip strength is widely used as a measure of muscle strength. Previous studies have shown inconsistent results regarding the role of vitamin D in hand grip strength. Here, we investigated hand grip strength and the effects of a yearlong vit...

Prematurity has been associated with impaired parasympathetic cardiac regulation later in life. Changes in heart rate (HR) and heart rate variability (HRV) may indicate a risk for future cardiac dysfunction. The putative role of Vitamin D on cardiac autonomic function in individuals born preterm (PT) remains unknown. This study involves monitoring...

The number of studies on the effects of mindfulness on healthcare professionals is increasing. The main aim of this study was to collate the quantitative results of original studies analyzing the effects of mindfulness-based interventions on a variety of outcomes in medical students. We also analyzed how the study design and characteristics of the...

Background This paper proposes a novel approach to the development of competence-oriented higher education, a national transformation aimed at harmonising and digitising undergraduate medical and dental education in Finland. Methods We apply phenomenography as a viable qualitative method for medical education research. To better understand medical...

BACKGROUND Electronic health care (eHealth) services are an increasing part of health care services. The digitalizing health care service system is creating new skills needs and challenges for medical education. Knowledge of students’ competence levels and abilities is important when teaching is being developed. OBJECTIVE The aim of this study was...

Objective The aim of this study was to analyze the usefulness of myeloid-related protein 8/14 (MRP8/14) in the prediction of disease course in a real-world setting for patients with new-onset juvenile idiopathic arthritis (JIA), to identify the relationship between MRP8/14 and disease activity using the physician’s global assessment of disease acti...

Background Today’s professionals need to be capable of independent information retrieval, teamwork, and lifelong learning. To meet these demands, more active learning methods are needed in university teaching. Team-based learning (TBL) is a learner-centered method which enables activation of students in large classes. Objective The aim of this stu...

Objective: The aim of this study was to analyze the usefulness of myeloid-related protein 8/14 (MRP8/14) in the prediction of disease course in a real-life setting for patients with new-onset juvenile idiopathic arthritis (JIA), to identify the relationship between MRP8/14 and disease activity using the physician’s global assessment of disease acti...

Digitalisaation myötä terveydenhuollon toiminnot muuttuvat nopeasti, ja sähköiset työkalut sekä pal-velut ovat jo arkipäivää. Vaikutukset näkyvät koulutustarpeena, koska terveydenhuollon ammattilaisten digiosaaminen tulee turvata. Lääkärien peruskoulutuksen tulisi sisältää etälääketiedettä ja sähköisen terveydenhuollon palveluja (e-health) koskevaa...

Background Caesarean section (CS) has been associated with an increased risk of subsequent atopic diseases, particularly asthma and respiratory allergies, but controversial findings have also been reported. Our aim was to clarify the association between the delivery mode and longitudinal (atopic) outcomes. Methods The target population was identif...

Background In genetic studies and selected study populations, parental atopy has been associated with atopic diseases in offspring. Our aim was to identify the association between parental atopic diseases and the offspring's atopic sensitization and food allergies, and their effect modifications due to the offspring's sex. Methods The study popula...

Objective: To evaluate the association between potential exposure to different pollen concentrations at the 11th fetal week and subsequent clinical atopic diseases. Study design and setting: Parents of 1- to 4-year-old children (N = 3035) returned a questionnaire regarding physician-diagnosed atopic diseases. The children were born between 2001...

MEDigi is a nationwide Finnish project that aims to develop and implement digital teaching, learning and assessment solutions and to provide possibilities for national harmonization of undergraduate medical and dental education in Finland. The MEDigi project will investigate the options and feasibility of a common national digital online platform a...

Background: The temporal sequence in which allergic sensitization to different allergens emerges is not well characterized at the level of general population. Objective: We describe the incidence patterns of atopic sensitization to different allergens from birth up to 12 years of age in an unselected Finnish population. Methods: The study popu...

Background: The optimal age for the introduction of solid foods for infants has long been a controversial issue. Objective: This study aims to determine whether the early introduction of semisolid foods influences the incidence of food allergy or atopic dermatitis among preterm infants. Methods: Retrospective data from 464 preterm infants born...

Aim A number of studies have clarified the tolerance mechanisms and risk factors for food allergies. Our aim was to explore food allergy symptoms by target organs, together with the risk factors and how to prevent food allergies and induce tolerance. Methods We carried out a thorough review of studies on paediatric food allergies published in the...

Introduction and objectives: Whether the guidelines on infant nutrition, food allergy and atopic dermatitis confer real health benefits in practice at the population level has not been deeply studied. We aimed here to characterize the knowledge, attitudes, and perceptions regarding these issues among primary health care professionals. In addition,...

Aim: This study investigated oral immunotherapy for children aged 6-18 years with wheat allergies. Methods: Well-cooked wheat spaghetti was given to 100 children with wheat allergies every day for 17 weeks, increasing from 0.3mg to 2,000mg of wheat protein, followed by three-month and nine-month maintenance phases. Blood samples were taken befor...

Background: Children whose 11(th) fetal week falls in pollen season (spring) reportedly have an increased risk of sensitisation to food allergens. No such finding has been reported for pet allergens. Objective: The aim of the study was to 1) evaluate the incidence of pet (dog and cat) sensitisation according to the season of the 11(th) fetal wee...

Background: Tubulointerstitial nephritis (TIN) is an inflammatory disease of unknown pathogenesis. To evaluate a possible role of regulatory T cells (Tregs) in the pathophysiology of TIN with (TINU) and without uveitis, we investigated the presence and quantity of FOXP3(+) T regulatory lymphocytes in diagnostic kidney biopsies from pediatric patie...

Background: The NF-κB signaling pathway is a key regulator of immune responses. Accordingly, mutations in several NF-κB pathway genes cause immunodeficiency. Objective: We sought to identify the cause of disease in three unrelated Finnish kindreds with variable symptoms of immunodeficiency and autoinflammation. Methods: We applied genetic link...

First-line treatments of bullous pemphigoid (BP) are topical and systemic glucocorticoids (GC). The actions of GC are mediated by glucocorticoid receptors (GR), which exist in several isoforms, of which GRα and GRβ are the most important. In many inflammatory diseases, up-regulation of GRβ is associated with GC insensitivity. The aims of this study...

Our aim was to study whether the aberrant amount or function of regulatory T cells is related to the development of type 1 diabetes (T1D) in children. We also set out to investigate the balance of different T-cell subtype markers during the T1D autoimmune process. Treg cells were quantified with flow cytometric assay and the suppression capacity wa...

The NFkB signaling pathway is a master regulator of the immune response. Recently, dominant mutations in NFKB2 have shown to cause antibody deficiency with adrenal insufficiency. We investigated two families with antibody deficiency and autoinflammatory features, with onset in teenage years and early adulthood (Fig. 1 and Table 1). In family 1, all...

AimsOur aim was to study whether immune responses to wheat-based proteins are related to the development of type 1 diabetes.Methods We analysed proliferative T-cell responses after in vitro gliadin, gluten, whole wheat, and tetanus toxoid stimulation with a carboxyfluorescein succinimidyl ester (CFSE) based T-cell proliferation assay in children at...

The signal transducer and activator of transcription (STAT) family of transcription factors orchestrate hematopoietic cell differentiation. Recently, mutations in STAT1, STAT5B, and STAT3 have been linked to development of immunodysregulation polyendocrinopathy enteropathy X-linked-like syndrome. Here, we immunologically characterized 3 patients wi...

Although most infants will recover from food allergy within the early years of life, at least one fifth will carry on with the disease until school age. Recent studies have managed to develop increased tolerance in children with food allergy by food hyposensitization with slowly increasing orally administered doses. In these studies either complete...

To evaluate the utility of GAD antibodies (GADAs) and islet antigen-2 antibodies (IA-2As) in prediction of type 1 diabetes over 27 years in the general population and to assess the 6-year rates of seroconversion. A total of 3,475 nondiabetic subjects aged 3-18 years were sampled in 1980, and 2,375 subjects (68.3%) were resampled in 1986. All subjec...

The forkhead DNA-binding protein FOXP3 is critical for the development and suppressive function of CD4(+)CD25(+) regulatory T cells (T(REG)), which play a key role in maintaining self-tolerance. Functionally, FOXP3 is capable of repressing transcription of cytokine genes regulated by NFAT. Various mechanisms have been proposed by which FOXP3 mediat...

The mechanisms leading to thyroid autoimmunity are largely unknown. Our objective was to assess the role of environment in the development of thyroid autoimmunity. Prevalence of thyroid autoantibodies in two neighboring populations living in completely different socioeconomic circumstances (Russian Karelia and Finland) was studied. We studied two p...

We sought to study the prevalence of autoantibodies to various islet cell antigens in the background population of two neighboring countries with a sixfold difference in the incidence of type 1 diabetes. Serum samples were obtained from 3,652 nondiabetic schoolchildren in Finland and from 1,988 schoolchildren in the adjacent Karelian Republic of Ru...

Our aim was to evaluate the predictive value of gestational diabetes mellitus (GDM), diabetes-associated autoantibodies, and other factors for development of clinical diabetes later in life. In this case-control study the presence of autoantibodies was studied in 435 women with GDM and in healthy matched control subjects. The need for exogenous ins...

To generate predictive models for the assessment of risk of type 1 diabetes and age at diagnosis in siblings of children with newly diagnosed type 1 diabetes. Cox regression analysis was used to assess the risk of progression to type 1 diabetes, and multiple regression analysis was used to estimate the age at disease presentation in 701 siblings of...

To describe the nutritional status in patients with screen-detected celiac disease (CD). Nutritional status was assessed by serum tests and anthropometric measures in 26 subjects (16 to 25 years of age) with biopsy-proven CD and 29 healthy control subjects (16 to 21 years of age) with negative tissue transglutaminase antibodies (16 to 22 years of a...

We observed 42 initially non-diabetic siblings of affected children to characterize the humoral immune response to the 65 kDa isoform of glutamic acid decarboxylase (GAD65) in preclinical type I diabetes. During the observation period with a mean duration of 9·6 years 21 siblings progressed to type I diabetes. The humoral immune response to GAD65 w...

We measured the circulating concentrations of the soluble forms of intercellular adhesion molecule-1, ICAM-1 (sCD54) and L-selectin (sCD62L) in 104 non-diabetic Finnish schoolchildren testing positive for one or more diabetes-associated autoantibodies and in 104 autoantibody-negative children to elucidate the relationship between soluble adhesion m...

To define the dynamics of preclinical type 1 diabetes in siblings of affected children and to characterize the siblings experiencing a progressive process. From 801 families taking part in the "Childhood Diabetes in Finland" (DiMe) Study, 715 initially unaffected siblings were graded into four stages of preclinical type 1 diabetes based on the init...

Wheat, rye, and barley proteins induce celiac disease, an autoimmune type of gastrointestinal disorder, in genetically susceptible persons. Because the disease may be underdiagnosed, we estimated the prevalence of the disease and tested the hypothesis that assays for serum autoantibodies can be used to detect untreated celiac disease and that posit...

We set out to study the association between human leukocyte antigen-defined genetic disease susceptibility and the stage of preclinical type 1 diabetes and whether genetic predisposition affects the natural course of preclinical diabetes in initially nondiabetic siblings of affected children. A total of 701 initially unaffected siblings were graded...

This prospective case-control study aimed at evaluating the time course of serum concentrations of soluble adhesion molecules; intercellular adhesion molecule-1 and L-selectin in siblings with signs of pre-clinical Type 1 diabetes in order to relate these concentrations to autoantibody status and to assess whether these markers could discriminate b...

The clinical manifestation of type 1 diabetes mellitus is preceded by an asymptomatic prodromal period called prediabetes or preclinical diabetes. It may last from a few months to several years, during which the autoimmune destruction of the insulin-producing β-cells in the pancreas progresses. The genes on the human leukocyte antigen (HLA) and ins...

The clinical manifestation of type 1 diabetes mellitus is preceded by an asymptomatic prodromal period called prediabetes or preclinical diabetes. It may last from a few months to several years, during which the autoimmune destruction of the insulin-producing β-cells in the pancreas progresses. The genes on the human leukocyte antigen (HLA) and ins...

To assess the role of HLA-defined genetic diabetes susceptibility in the appearance of signs of beta-cell autoimmunity in a series of children derived from the general population. Tests for five HLA DQB1 alleles and four diabetes-associated autoantibodies were carried out on 1,584 older sibs of infants with an increased HLA-defined genetic risk of...

The aim of this study was to evaluate the frequency and predictive value of diabetes-associated autoantibodies, such as islet cell antibodies (ICA) and autoantibodies to insulin (IAA), GAD65 (GADA), and the IA-2 molecule (IA-2A) in genetically susceptible children from the general population during the first 2 yr of life. Of 12,170 newborn infants,...

We have studied the relationship between diabetes-associated autoantibodies and various HLA genotypes and alleles in patients with newly diagnosed type 1 diabetes, in non-diabetic siblings and in children representing the general population to test the hypothesis that specific HLA genes regulate the humoral immune response to various autoantigens....

Islet cell antibodies (ICA) represent a heterogenous group of autoantibodies to diabetes-associated antigens, including glutamic acid decarboxylase (GAD) and the IA-2 protein. The objectives of the present study were to compare the prevalence of autoantibodies to known biochemically characterized autoantigens between ICA-positive non-diabetic paren...

Cord blood samples were collected from 1002 consecutive births at Turku University Hospital to study the prevalence and fate of type 1 diabetes-associated autoantibodies in newborn infants of unaffected mothers. The samples were analysed for cytoplasmic islet cell antibodies (ICA), autoantibodies to the 65 kD isoform of glutamic acid decarboxylase...

The possible relation between HLA-DQ genotypes and both frequencies and levels of autoantibodies associated with IDDM was assessed by examining HLA-DQB1 alleles and antibodies to islet cells (ICA), insulin (IAA), glutamic acid decarboxylase (GADA) and the protein tyrosine phosphatase-related IA-2 molecule (IA-2A) in 631 newly diagnosed diabetic chi...

To study the dynamics of disease-associated humoral immune responses, we analyzed autoantibodies to the IA-2 protein (IA-2A), glutamic acid decarboxylase (GADA), and insulin (IAA) and also islet cell antibodies (ICA) in a population-based, prospective, representative series of 710 siblings (<20 years of age) of children with type 1 diabetes. Positi...

We studied the pattern of type 1 diabetes-associated autoantibodies during pregnancy and the transplacental transfer of these autoantibodies to the fetal circulation and searched for possible signs of prenatal induction of β-cell autoimmunity in newborn infants. The population comprised 208 mothers and their newborn infants. Seventy-four of the mot...

Little is known about the timing of the etiological events and the preclinical process of type 1 diabetes during the first years of life in the general population. In this population-based prospective birth cohort study, the appearance of diabetes-associated autoantibodies as a sign of β-cell autoimmunity and the development of type 1 diabetes were...

We measured the concentrations of the soluble forms of the intercellular adhesion molecule-1 (sICAM-1) and L-selectin in 95 autoantibody-positive siblings of children with type 1 diabetes and 95 sex- and age-matched siblings testing negative for diabetes-associated autoantibodies to assess the possible role of soluble adhesion molecules as markers...

The increased prevalence of autoantibodies in patients with epilepsy has been traditionally regarded to be a consequence of antiepileptic drugs. The purpose of this study was to measure autoantibodies in well-defined groups of patients with seizures to determine the effects of epilepsy and antiepileptic medications on the presence of autoantibodies...

To assess whether there are any differences in genetic, autoimmune, or clinical features between type 1 diabetes presenting in childhood and that diagnosed later. We studied 352 individuals (252 children and adolescents <20 years of age and 100 adults > or =20 years of age) manifesting clinical signs of type 1 diabetes over a period of 7.5 years at...

Autoantibodies to glutamic acid decarboxylase (GAD-A) are present in type 1 diabetes and stiff man syndrome (SMS), and have also been reported in cerebellar ataxia. Epilepsy was present in 4 of 19 patients with SMS and GAD-A, implying that epilepsy sometimes is associated with anti-GAD autoimmunity. The authors investigated the prevalence of GAD-A...

Recent prospective studies have documented serologically an increased frequency of enterovirus infections in prediabetic children, indicating that these infections may initiate and accelerate the beta-cell damaging process several years before the clinical manifestation of type 1 diabetes. The aim of the present study was to establish whether these...

Recent prospective studies have documented serologically an increased frequency of enterovirus infections in prediabetic children, indicating that these infections may initiate and accelerate the beta-cell damaging process several years before the clinical manifestation of type 1 diabetes. The aim of the present study was to establish whether these...

To study temporal changes in positivity for autoantibodies associated with Type I (insulin-dependent) diabetes mellitus and the relations between these antibodies, HLA-DQB1-risk markers and first-phase insulin response (FPIR) in non-diabetic schoolchildren. The stability of the antibody status over 2 years was assessed in 104 schoolchildren initial...

To evaluate the emergence of diabetes-associated autoantibodies in young children and to assess whether such antibodies can be used as surrogate markers of type 1 diabetes in young subjects at increased genetic risk, we studied 180 initially unaffected siblings (92 boys and 88 girls) of children with newly diagnosed type 1 diabetes. All siblings we...

To study the characteristics of type 1 diabetes in very young children. Clinical outcome, islet cell antibodies (ICA), insulin autoantibodies (IAA), antibodies against GAD (GADA), IA-2 antibodies (IA-2A), and HLA-DQB1-defined genetic risk were analyzed in 35 children diagnosed with type 1 diabetes before 2 years of age and compared with those in 14...

The relationships between genetic markers and disease-associated autoantibodies were studied in an unselected population of 701 siblings of children with type 1 diabetes, and the predictive characteristics of these markers over a period of 9 years were determined. Increased prevalences of all the antibodies were closely associated with HLA identity...

Glutamic acid decarboxylase antibodies are present in some patients with therapy-resistant epilepsy. The authors measured glutamic acid decarboxylase antibodies in an unselected population of 114 children with different types of epilepsy. Three children with temporal lobe epilepsy and six children with various other types of epilepsy had intractabl...

To assess whether it is clinically relevant to classify siblings of children with recent-onset type 1 diabetes mellitus (T1DM) into various stages of preclinical diabetes, and to compare the risk of developing clinical disease and the time to diagnosis between these stages. From a total of 801 families taking part in the Childhood Diabetes in Finla...

Objectives To assess whether it is clinically relevant to classify siblings of children with recent-onset type 1 diabetes mellitus (T1DM) into various stages of preclinical diabetes, and to compare the risk of developing clinical disease and the time to diagnosis between these stages. Study Design From a total of 801 families taking part in the Ch...

Enterovirus infections have been implicated in the pathogenesis of IDDM in a number of studies. The aim of the present study was to evaluate whether the cellular immune response to enterovirus antigens is abnormal in children who test positive for IDDM-associated autoantibodies. Lymphocyte proliferation responses were analysed to enterovirus antige...

We analyzed 747 children, younger than 15 yr of age, with newly diagnosed diabetes, for antibodies to glutamic acid decarboxylase (GADA), the IA-2 protein (IA-2A), insulin (IAA), and islet cells, to evaluate the influence of positivity for GADA, IA-2A, IAA, or multiple (> or = 3) autoantibodies at diagnosis, on the clinical presentation and natural...

We analyzed 747 children, younger than 15 yr of age, with newly diagnosed diabetes, for antibodies to glutamic acid decarboxylase (GADA), the IA-2 protein (IA-2A), insulin (IAA), and islet cells, to evaluate the influence of positivity for GADA, IA-2A, IAA, or multiple ($3) autoantibodies at diagnosis, on the clinical presentation and natural cours...

The possible relation between HLA-DQ genotypes and both frequencies and levels of autoantibodies associated with IDDM was assessed by examining HLA-DQB1 alleles and antibodies to islet cells (ICA), insulin (IAA), glutamic acid decarboxylase (GADA) and the protein tyrosine phosphatase-related IA-2 molecule (IA-2A) in 631 newly diagnosed diabetic chi...

To investigate whether type 1 diabetes in man is associated with a preferential Th1/Th2 response, and whether autoantibodies to one of the main autoantigens would reflect such a response, we characterized the immunoglobulin isotype profile to the 65-kDa isoform of glutamic acid decarboxylase (GAD65) in siblings to IDDM patients. Samples obtained fr...

To investigate whether type 1 diabetes in man is associated with a preferential Th1/Th2 response, and whether antoantibodies to one of the main autoantigens would reflect such a response, we characterized the immunoglobulin isotype profile to the 65-kDa isoform of glutamic acid decarboxylase (GAD65) in siblings to IDDM patients. Samples obtained fr...

To study the persistence of Type I (insulin-dependent) diabetes mellitus associated autoantibodies and their relation to genetic risk markers and clinical characteristics of the disease after clinical manifestation, serum samples were obtained from 90 children and adolescents at diagnosis and 2, 5 and 10 years later. The samples were analysed for i...

In a prospective multicentre study described previously on prediabetic events in siblings of index cases with insulin-dependent diabetes mellitus, 31 children developed clinical diabetes during the observation period and 51 children seroconverted for islet cell antibodies or insulin autoantibodies. By using nonserotype specific EIA and RIA, it has...

Evidence from case-control studies for the diabetogenicity of introduction of cow's milk-based formulas at early age in infancy is inconclusive. We followed siblings of children with Type 1 diabetes mellitus (Type 1 DM) to investigate a possible relationship between cow's milk consumption during infancy or later in childhood and the emergence of di...

In a prospective multicentre study described previously on prediabetic events in siblings of index cases with insulin-dependent diabetes mellitus, 31 children developed clinical diabetes during the observation period and 51 children seroconverted for islet cell antibodies or insulin autoantibodies. By using nonserotype specific EIA and RIA, it has...