The thesis The analysis of genetic factors of breast cancer by NGS deals with the current serious problematics of breast cancer from the perspective of genetic predisposition. Breast cancer is one of the most common tumors in women. Every year more than 7000 women are diagnosed with this disease and the mortality rate in the Czech Republic is nearly 2000 cases. Of the total number of patients diagnosed with breast cancer, approximately ten percent of patients have congenital mutations in one of the predisposing genes that cause a significantly increased risk of developing a cancer. More than half of these mutations occur in germline mutations of the BRCA1 or BRCA2 genes, others include a number of other genes, eg tp53, CDH1, PTEN, STK11, ATM, PALB2, CHEK2.Early diagnosis and identification of persons with increased risk of developing breast cancer is of key importance for their inclusion in preventive programs. Therefore, the thesis aims to testing genes that can cause a breast cancer. In the thesis, 219 known and candidate predisposition genes were analyzed in a group of 263 non-selected breast cancer patients using a targeted panel NGS, the Illumina platform. Selected identified suspect variants were further confirmed by Sanger sequencing. The aim of this work was also a mutational analysis of...

O presente estudo aborda o tema da eugenia - ciência que pregava a aplicação de práticas de melhoramento e aprimoramento da espécie humana - e suas influências nas pesquisas e práticas médicas no início do século XX. A eugenia consistiu em uma importante estratégia para enfrentamento da diversidade imposta nas cidades, contribuindo para a construção da ordem e civilidade, baseada no progresso e na superioridade moral e física dos indivíduos. Ao defender a reprodução humana controlada para obter uma raça pura, pregava a eliminação dos \"inferiores\" e \"degenerados\" por meio de práticas de saneamento, exclusão social, isolamento compulsório, controle de casamentos e, em alguns casos, esterilização involuntária. A transição dos séculos XIX e XX marcou o período de ascensão do movimento eugenista, onde os médicos ganharam posição de destaque como representantes da ciência, exercendo influência sobre diferentes esferas da sociedade, com o objetivo de sanear o meio e oferecer condições para a elevação da raça. O objetivo deste estudo é investigar a influência da eugenia nos estudos e práticas médicas entre 1920 e 1939, a partir da produção das teses doutorais da antiga Faculdade de Medicina e Cirurgia de São Paulo (atual Faculdade de Medicina da Universidade de São Paulo), especificando os elementos relacionados às práticas eugênicas lamarckistas (positivas) e mendelistas (negativas). Para a realização do estudo, foram realizados levantamento e análise de 45 teses doutorais, analisadas sob os referenciais metodológicos pautados no conceito da lógica histórica (Thompson, 1981), do paradigma indiciário (Ginzburg, 1989) e das leituras como representações (Chartier, 1991). A pesquisa encontra subsídios nos estudos em Saúde Coletiva, buscando fornecer elementos no sentido de compreender os princípios do discurso médico-eugênico nas práticas médicas e educacionais do período, contribuindo para a análise de processos de rupturas e permanências históricas nas práticas em saúde. As teses doutorais podem ser consideradas representativas na apresentação das temáticas médico-eugênicas, que estavam presentes, de alguma forma, na estrutura de ensino da faculdade, reforçando a importância atribuída à eugenia no meio científico da época / This study addresses the theme of eugenics - science that proclaimed the application of practices for improvement and enhancement of human species - and its influences on medical practices and research in the early 20th century. Eugenics consisted of an important strategy for coping with the diversity imposed in cities, contributing to the foundation of order and civility, based on progress and moral and physical superiority of individuals. By supporting the idea of controlled human reproduction to obtain a pure race, it preached the elimination of the \"inferior\" and \"degenerate\" by means of sanitation practices, social exclusion, compulsory isolation, marriage control, and, in some cases, involuntary sterilization. The transition of the 19th and 20th centuries has marked the period of ascension of the eugenic movement, in which doctors have gained prominent position as science representatives, exerting its influence on diverse spheres of society, aiming to sanitize the environment and offering conditions for the rise of the race. The objective of this study is to investigate the influence of eugenics on medical studies and practices between 1920 and 1939, from the production of doctoral theses of the former Medicine and Surgery College of São Paulo [Faculdade de Medicina da Universidade de São Paulo] (currently Medicine College of São Paulo University [Faculdade de Medicina da Universidade de São Paulo]), specifying elements related to lamarckist (positive) and mendelist (negative) eugenic practices. In order to fulfil the study, 45 doctoral theses were surveyed and analyzed according to the methodological guidelines based on the concept of historical logic (Thompson, 1981), the indiciary paradigm (Ginzburg, 1989) and the readings as representations (Chartier, 1991). The research finds subsidies in Collective Health studies, seeking to provide elements to understand the principles of medical-eugenic discourse in the medical and educational practices of the period, contributing to the analysis of processes of historical rupture and maintenance in health practices. The doctoral theses can be considered representative in the presentation of the medical-eugenic themes that were present, in some way, in the teaching structure of the college, reinforcing the importance attributed to eugenics in the scientific environment of the time

Made available in DSpace on 2016-08-10T10:38:58Z (GMT). No. of bitstreams: 1 ISABELLA LACERDA FERNANDES.pdf: 1467834 bytes, checksum: 985b4aa7bf961993ef7672d3838bc086 (MD5) Previous issue date: 2015-03-31 / Microsatellite markers are short sequences, repetitive, highly polymorphic and hereditary present in the DNA, which follow the Mendelian pattern of segregation. Due to its haplotype heritage has been used to trace the paternal line to be passed from generation to generation without any changes, except in cases of mutation. The stepwise mutation model is more acceptable to mutation in microsatellite markers, assuming that each mutational event the length of a microsatellite changes by one or a few repeating units due to slippage process, which occurs during replication DNA. This study aimed to estimate the rates of change of microsatellite markers of the Y chromosome in a sample of the population and its implications in human identification process. It is a molecular study, which was conducted at Biocroma Laboratory in partnership with LaGene and Replicon in Goiânia-Goiás. Samples of study were selected from 80 cases of investigation of paternity by DNA analysis, undergo mutation analysis in the Y chromosome haplotypes with molecular amplification system PowerPlex® Y23 System - Promega Corporation. Were identified 15 records of germline mutations in the Y chromosome between alleged parents and children related to suspected samples. The results have identified 9 mutations gain and 6 mutations loss of repetitions numbers. The DYS576 marker had the highest number of reported mutations (20%), followed by DYS570, which identified two mutations (13.33%). The markers DYS389 II, DYS391, DYS481, DYS549, DYS438, DYS439, DYS393, DYS458, DYS385 a - b DYS456 showed only 1 (6.66%) mutation record each. In the other markers, DYS389 I, DYS448, DYS19, DYS533, DYS437, DYS635, DYS390, DYS392, DYS643 and Y-GATA-H4 mutations were not identified in the samples analyzed in this study. Thus the identification of mutations increases the tools that are used in genetic analysis link laboratories and can deliver a more reliable result minimizing potential errors in the analyzes. / Os marcadores microssatélites são sequências curtas, repetitivas, altamente polimórficas e hereditárias presentes no DNA, que seguem o padrão mendeliano de segregação. Devido a sua herança haplotípica tem sido utilizado para rastrear a linhagem paterna por ser passado de geração em geração sem nenhuma alteração, exceto em casos de mutação. O modelo step-wise mutation é o mais aceito para mutação nos marcadores microssatélites, admitindo-se que, a cada evento mutacional o comprimento de um microssatélite altera por uma ou poucas unidades de repetição devido ao processo de slippage, que ocorre durante a replicação do DNA. Este trabalho teve como objetivo estimar as taxas de mutações dos marcadores microssatélites do cromossomo Y em uma amostra da população brasileira e suas implicações no processo de identificação humana. Trata-se de um estudo molecular, que foi conduzido no Laboratório Biocroma em parceria com o LaGene e Replicon em Goiânia-Goiás. As amostras de estudo foram selecionadas de 80 casos de investigação de paternidade pela análise do DNA, submetidos a análise de mutações nos haplótipos do cromossomo Y com o sistema de amplificação molecular PowerPlex® Y23 System Promega Corporation. Foram identificados 15 registros de mutações germinativas no cromossomo Y entre supostos pais e supostos filhos referentes às amostras analisadas. Os resultados obtidos permitiram identificar 9 mutações de ganho e 6 mutações de perda de números de repetições. O marcador DYS576 apresentou o maior número de mutações registrados (20%), seguido pelo DYS570, que permitiu identificar 2 mutações (13,33%). Os marcadores DYS389 II, DYS391, DYS481, DYS549, DYS438, DYS439, DYS393, DYS458, DYS385 a-b e DYS456 apresentaram apenas 1 (6,66%) registro de mutação cada. Nos demais marcadores, DYS389 I, DYS448, DYS19, DYS533, DYS437, DYS635, DYS390, DYS392, DYS643 e Y-GATA-H4 não foram identificadas mutações nas amostras analisadas neste estudo. Desta forma a identificação das mutações aumenta as ferramentas que são utilizadas nos laboratórios de análise de vínculo genético e que podem garantir um resultado mais confiável minimizando possíveis erros nas análises.

O objetivo deste trabalho foi avaliar se estudantes de graduação em Psicologia demonstram compreensão crítica em relação ao secular debate entre hereditariedade e ambiente, sobretudo a partir de temas que fazem parte do campo da Psicologia do Desenvolvimento. Para tanto foi elaborado um questionário com 12 situações-problema, com quatro opções de respostas, sendo três referentes às concepções de desenvolvimento inatista, ambientalista e interacionista e uma indicativa do desconhecimento da resposta (não sei ou não tenho ideia a respeito). Participaram do estudo 462 graduandos em Psicologia, de 1º e 5º anos, de quatro Instituições de Ensino Superior privadas, localizadas no Estado de São Paulo. Os resultados foram analisados em função das variáveis sexo, idade, fase do curso, outro curso superior, Psicologia no Ensino Médio e das interações entre as variáveis sexo x fase do curso, idade x fase do curso, fase do curso x IES e IES x fase do curso. A análise inferencial dos resultados foi realizada por meio da estatística não paramétrica, calculando-se o qui-quadrado e o coeficiente de contingência. Os dados sugerem que a variável idade foi a mais influente e as interações mais relevantes foram entre IES x Fase do curso; Fase do curso x IES e sexo x fase do curso. Os dados do coeficiente de contingência indicaram que o grau de associação entre as variáveis analisadas variou de fraco a moderado. A concepção interacionista predominou na maior parte dos resultados, mas nem sempre influenciada pela fase do curso, como era a hipótese inicial. Além disso, a depender do tema da questão, as respostas ambientalistas chegaram a superar as interacionistas e, em alguns casos, a concepção inatista também se mostrou relevante para os participantes. Ou seja, houve certa variabilidade nas escolhas das concepções em função dos problemas apresentados, sugerindo que o estudante de Psicologia provavelmente tende a escolher a explicação para o problema de acordo com o contexto e não com uma base epistemológica (ou paradigma) coerente. Sendo assim, pode-se concluir que o graduando ainda precisa aprimorar sua capacidade de transferir o conhecimento adquirido em um paradigma para outras situações que não são comumente associadas a ele, desenvolvendo maior flexibilidade de pensamento. A presença de resultados contraintuitivos em algumas questões também demonstra que existem fatores ideológicos que interagem com a aquisição do conhecimento científico pelo estudante. Finalmente, a pluralidade de epistemologias/paradigmas no campo da Psicologia, bem como a própria diversidade de concepções a respeito do conceito de interação, podem ser fatores que dificultam o posicionamento crítico do graduando, uma vez que a explicitação do conhecimento e a relação da teoria com a base epistemológica pode não estar clara. Concluise, portanto, que, na formação do psicólogo é preciso articular melhor a relação entre epistemologia, prática e pensamento crítico, nos cursos de graduação / This thesis aims at assessing whether undergraduate Psychology students indicate critical thinking in relation to the continuous debate between heredity and environment, especially from the developmental psychology perspective. To that end, we devised a questionnaire with twelve problem situations and four possible answers each. Three of these answers referred to three distinct perspectives of development: innatism, environmentalism, and interactionism. A fourth answer indicated that the subject did not know how to respond the question. Four hundred and sixty-two undergraduate Psychology students participated, in their first to their fifth year in the course, from four private universities from the State of São Paulo. The results were analyzed based on a series of variables: gender, age, stage of the course, having other undergraduate degree, Psychology in high school, and on the interactions among the variables gender x stage of the course, age x stage of the course, stage of the course x university, and university x stage of the course. Inferential analysis of the results was conducted by means of non-parametric statistics, by calculating the chi-square and the contingency coefficient. Data suggest that the variable age was the most influential, and the most relevant interactions were among university x stage of the course, stage of the course x university, and gender x stage of the course. Contingency coefficient data indicate that the grade of interaction among the analyzed variables varied from weak to moderate. The interactionist conception predominated in most of the results, although not always influenced by the stage of the course, which was the initial hypothesis. Furthermore, depending on the topic of the question, the environmentalist answers outnumbered the interactionist ones and, in some cases, the innatist conception was also relevant to the participants. In other words, there was certain variability in the choices of conception according to the problems presented, suggesting that the Psychology student tends to choose the explanation of the problem according to the context and not under a coherent epistemology (or paradigm). Thus, it might be argued that the undergraduate student still needs to improve his capability of transferring knowledge acquired under a paradigm to other situations uncommonly associated to it, leading to the development of a more flexible reasoning. The presence of counterintuitive results in some of the questions also shows that there are ideological factors that interact with the students acquisition of scientific knowledge. Lastly, the plurality of epistemologies/paradigms in the field of psychology, as well as the very diversity of understandings of the concept of interaction might be factors that make the students critical positioning more challenging, since externalizing knowledge and the relation between theory and its epistemological grounds might not be clear. Therefore, the psychologist education, namely the undergraduate courses, should require a better relation between epistemology, practice, and critical thinking

The dissertation examines the interrelationship between professional and public discourses on Jewish health and the politics of citizenship in Russia across the revolutionary divides of the early twentieth century. In Russia, like in other countries of the time, medical consensus held that Jews exhibited different rates of various diseases compared to Gentiles, such as a higher incidence of diabetes and a lower rate of syphilis. The validity of such data aside, the production and interpretation of these statistics reveal how the criteria of civil enfranchisement and group identity changed over the period in question. Debates about Jewish health at the time addressed two major themes: whether Jews could be full-fledged citizens and whether they constituted a particular ethnic/"racial" group. However, as the dissertation argues, it was concepts of citizenship that generated racial discourse and nationalist ideologies, in this case, and not the other way around. Two concepts of race coexisted in Russian professional and public discourses during the nineteenth and early twentieth centuries, one historical-cultural and the other biological. This dissertation demonstrates that the former was much more politically and intellectually productive than the latter. Biological concepts of race had limited currency at the time and, as a rule, were subordinated to the discourse of ethnicity. At the same time, notions of civilization and the autonomous personality were crucial for debates about Jewish health, Jewish civil status, and the politics of formal and informal citizenship in Russia before 1917. After the Bolshevik revolution, these concepts continued to affect the state's social policies, even though they became divorced from the formal criteria of citizenship. Since the Russian empire and, in a different manner, the early Bolshevik state did not have universal and uniform citizenship based on the idea of natural rights, this study offers useful comparative material for the history of citizenship in general, and the politics of citizenship in empires and composite states in particular. It also offers a contextual, underdeterministic interpretation of the political significance of "race" which departs from established teleological and deterministic narratives of the history of racial thought. / History

Žmonių populiacijų tyrimai atskleidžia jų fizinio pajėgumo genetinę įvairovę. Tokių ypatumų turi ir Lietuvos populiacija. Sportininkų individualaus genomo žinojimas ypač svarbus sporto teorijai, praktikai ir medicinai. Darbas skirtas svarbiausiems klausimams, susijusiems su genetinių veiksnių įtaka sportinio fizinio pajėgumo komponentams. Darbo metu buvo sukaupta Lietuvos didelio meistriškumo sportininkų imtis, kuri ištirta genetiškai ir pagal fenotipą. Sukurtoje Lietuvos didelio meistriškumo įvairių sporto šakų sportininkų DNR mėginių biobazėje sukaupta informacija apie sportininkų genotipus ir sportininkų fizinio išsivystymo bei funkcinio pajėgumo fenotipiniai duomenys. Parinkti stipriausi genai kandidatai, siejami su žmogaus fiziniu pajėgumu. Didelio meistriškumo sportininkai pirmą kartą Lietuvoje buvo tirti pagal 6 genų kandidatų DNR žymenų alelių, dažniausiai asocijuojamų su fiziniu pajėgumu, paplitimą. Tirtų genų kandidatų žymenų genotipų/alelių dažnių įvairovė išskirtose sportininkų grupėse ir bendroje Lietuvos populiacijoje turi savitumų. Visų tirtų Lietuvos sportininkų fizinio išsivystymo ir funkcinio pajėgumo rodikliai atitinka didelio meistriškumo sportininkų lygį. Fenotipinių rodiklių statistinė analizė parodė sportininkų organizmo įgimtus gebėjimus ir prisitaikymą prie fizinių krūvių. Kiekvienos išskirtos sporto šakų grupės sportininkams būdinga genotipų/alelių kombinacija. Tirtų genetinių variantų genotipai turi skirtingos įtakos vyrų bei moterų fiziniam... [toliau žr. visą tekstą] / The genetic diversity of physical capacity in the Lithuanian population has a pattern similar to that of other populations. The knowledge of the individual genomes of the athletes is especially important for sports theory, practice and medicine. This research is devoted to the issue of the effect of genetic factors on the components of sporting physical capacity. We have accumulated a sample of the Lithuanian elite athletes which was studied genetically according to a phenotype. We have created a DNA biobase of the Lithuanian elite athletes of various sporting disciplines and collected information about the genotypes and phenotypes of physical development and functional capacity of the athletes. This is the first time in Lithuania that the elite athletes were investigated according to allelic distribution of 6 candidate gene variants most associated with physical capacity. The genetic diversity of the physical capacity in the Lithuanian population has a pattern manifested by variation in the allele/genotype frequencies of the selected candidate gene markers in the Lithuanian athlete groups and general population. The indexes of physical development and functional capacity of the Lithuanian athletes correspond to the elite levels. Inherited qualities and adaptation to physical loads of the athletes can be assessed by statistical analysis of phenotypic indexes. Each group of athletes investigated had a typical genotype/allele combination. The genotypes of the gene variants... [to full text]

The genetic diversity of physical capacity in the Lithuanian population has a pattern similar to that of other populations. The knowledge of the individual genomes of the athletes is especially important for sports theory, practice and medicine. This research is devoted to the issue of the effect of genetic factors on the components of sporting physical capacity. We have accumulated a sample of the Lithuanian elite athletes which was studied genetically according to a phenotype. We have created a DNA biobase of the Lithuanian elite athletes of various sporting disciplines and collected information about the genotypes and phenotypes of physical development and functional capacity of the athletes. This is the first time in Lithuania that the elite athletes were investigated according to allelic distribution of 6 candidate gene variants most associated with physical capacity. The genetic diversity of the physical capacity in the Lithuanian population has a pattern manifested by variation in the allele/genotype frequencies of the selected candidate gene markers in the Lithuanian athlete groups and general population. The indexes of physical development and functional capacity of the Lithuanian athletes correspond to the elite levels. Inherited qualities and adaptation to physical loads of the athletes can be assessed by statistical analysis of phenotypic indexes. Each group of athletes investigated had a typical genotype/allele combination. The genotypes of the gene variants... [to full text] / Žmonių populiacijų tyrimai atskleidžia jų fizinio pajėgumo genetinę įvairovę. Tokių ypatumų turi ir Lietuvos populiacija. Sportininkų individualaus genomo žinojimas ypač svarbus sporto teorijai, praktikai ir medicinai. Darbas skirtas svarbiausiems klausimams, susijusiems su genetinių veiksnių įtaka sportinio fizinio pajėgumo komponentams. Darbo metu buvo sukaupta Lietuvos didelio meistriškumo sportininkų imtis, kuri ištirta genetiškai ir pagal fenotipą. Sukurtoje Lietuvos didelio meistriškumo įvairių sporto šakų sportininkų DNR mėginių biobazėje sukaupta informacija apie sportininkų genotipus ir sportininkų fizinio išsivystymo bei funkcinio pajėgumo fenotipiniai duomenys. Parinkti stipriausi genai kandidatai, siejami su žmogaus fiziniu pajėgumu. Didelio meistriškumo sportininkai pirmą kartą Lietuvoje buvo tirti pagal 6 genų kandidatų DNR žymenų alelių, dažniausiai asocijuojamų su fiziniu pajėgumu, paplitimą. Tirtų genų kandidatų žymenų genotipų/alelių dažnių įvairovė išskirtose sportininkų grupėse ir bendroje Lietuvos populiacijoje turi savitumų. Visų tirtų Lietuvos sportininkų fizinio išsivystymo ir funkcinio pajėgumo rodikliai atitinka didelio meistriškumo sportininkų lygį. Fenotipinių rodiklių statistinė analizė parodė sportininkų organizmo įgimtus gebėjimus ir prisitaikymą prie fizinių krūvių. Kiekvienos išskirtos sporto šakų grupės sportininkams būdinga genotipų/alelių kombinacija. Tirtų genetinių variantų genotipai turi skirtingos įtakos vyrų bei moterų fiziniam... [toliau žr. visą tekstą]

Colorectal cancer (CRC) is one of the most common cancer types and leading causes of cancer death worldwide. Since CRC is a heterogenic disease, there is a demand for increased knowledge of the underlying genetic and epigenetic mechanisms. The aim of this thesis was to investigate heredity and potential tumour markers in relation to prognosis. In paper I, survival of patients with CRC and a positive family history of CRC in first-degree relatives was analysed. Patients with colon cancer and positive family history of CRC had improved survival compared to patients with negative family history. This improvement in survival could not be explained by known clinico-pathological factors. In paper II, we investigated the prognostic value of Tryptophanyl t-RNA synthetase (TrpRS) in tissues from patients operated for CRC. Low protein expression of TrpRS in primary tumour tissues correlated with increased risk of recurrence and poorer survival. In paper III, the prognostic value of microsatellite instability (MSI) and the correlation to heredity for CRC in first-degree relatives was investigated. Patients with proximal colon cancer and MSI had improved cancer specific survival. There were no correlation between MSI and heredity. In paper IV, we evaluated the potential use of proximity ligation assay (SP-PLA) in patients with CRC, by simultaneous analysis of 35 proteins in only 5 μl plasma. SP-PLA is a suitable method for protein detection and might give valuable guidance in pursuing new prognostic and predictive tumour markers. However, none of the markers selected for present SP-PLA analyses gave better prognostic information than CEA. In conclusion, heredity is related to better survival independent of MSI in patients with CRC and MSI is associated with better prognosis in proximal colon cancer. Detection and increased knowledge of molecular mechanism in CRC is important, however it needs to be further investigated and validated in clinical use.

Issued also as Thesis (Ph. D.)--Columbia University. / Bibliography: p. 59-60.

A hereditariedade e a variação biológica são centrais para a evolução biológica. Apesar das diferentes abordagens sobre esse tema, sempre se mostra recorrente no discurso de cientistas, filósofos, historiadores e sociólogos da ciência a problematização do genecentrismo. Desse modo, uma questão relevante é entender o lugar do genecentrismo no pensamento evolutivo - é preciso perguntar como e por que esse tema tem sido problematizado de uma determinada maneira. Essa dissertação tem como objetivo principal, portanto, procurar as condições históricas que possibilitaram a organização do genecentrismo no pensamento evolutivo. A principal ideia defendida nesse estudo é de que a constituição do genecentrismo, e seu lugar central na teoria evolutiva, foram possibilitados pela emergência da racionalidade genética e pela construção de uma identidade genética intrínseca no início do século XX. A partir de evidências históricas, defendo também que a emergência da racionalidade genética permitiu enunciar muitas proposições novas, formando saberes e produzindo discursos, como a demonstração da seleção natural e uma síntese teórica da evolução biológica. Mas também a partir dela se operou “constrições” no conhecimento evolutivo, como a exclusão da Embriologia e a diminuição da importância de fatores ontogenéticos e ambientais. / Heredity and variation are central focus of evolutionary studies. Despite the different approaches to heredity and evolution, the gene-centered version of evolution is a central theme in the discourse of philosophers, historians and sociologists of science. Thereby, my aim here is to understand the place of gene-centered view in the evolutionary thought and to trace the historical conditions of possibility which set up this discourse. The main idea of this dissertation is that the origin of gene-centered view of evolution was made possible by the emergence of genetic rationality and the creation of ‘genetic identity’ at the turn of the twentieth century. Historical evidence is presented to support that the emergence of genetic rationality allowed new propositions to be made, forming knowledge and producing discourse in the evolutionary theory, as the demonstration of natural selection and a theoretical synthesis. But also from the genetic rationality there are effects of “evolutionary constriction", as the exclusion of Embryology from the Evolutionary Synthesis and the decrease importance of ontogenetic and environmental factors.