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70-524: Elvin Morton "Bunky" Jellinek (15 August 1890 – 22 October 1963), E. Morton Jellinek , or most often, E. M. Jellinek , was a biostatistician , physiologist , and an alcoholism researcher , fluent in nine languages and able to communicate in four others. The son of Markus Erwin Marcel Jellinek (1858–1939) and Rose Jellinek (1867–1966), née Jacobson (a.k.a. the opera singer Marcella Lindh ), he

140-442: A biological effect, a property known as potency . In medicine, efficacy is the capacity for beneficial change (or therapeutic effect ) of a given intervention (for example a drug, medical device , surgical procedure , or a public health intervention). Establishment of the efficacy of an intervention is often done relative to other available interventions, with which it will be compared. Specifically, efficacy refers to "whether

210-534: A biostatistician of Jellinek’s eminence would have been only too well aware of the "unscientific status" of the "dubiously scientific data that had been collected by AA members". In his 1960 book he identified five different types of alcoholism, and defined them in terms of their abnormal physiological processes: The "Jellinek curve" is derived from this classification of Jellinek, and it was named out of respect for Jellinek’s work. Jellinek later completely dissociated himself from this chart's representations; however it

280-506: A cash prize of US$ 5,000, as well as a bust of Jellinek with a personalized inscription. Substance Abuse Library and Information Studies: Proceedings of the 36th Annual SALIS Conference, (May 1, 2014). Biostatistician Biostatistical modeling forms an important part of numerous modern biological theories. Genetics studies, since its beginning, used statistical concepts to understand observed experimental results. Some genetics scientists even contributed with statistical advances with

350-419: A complex trial – with 199 subjects, divided randomly into four test groups – involving various permutations of the three drug constituents, with a placebo as a scientific control . Each group took a test remedy for two weeks at a time. The trial lasted eight weeks, by the end of which each group had taken each of the test drugs, albeit in a different sequence. Over the entire population of 199 subjects, 120 of

420-576: A consistent, coherent whole that could begin to be quantitatively modeled. In parallel to this overall development, the pioneering work of D'Arcy Thompson in On Growth and Form also helped to add quantitative discipline to biological study. Despite the fundamental importance and frequent necessity of statistical reasoning, there may nonetheless have been a tendency among biologists to distrust or deprecate results which are not qualitatively apparent. One anecdote describes Thomas Hunt Morgan banning

490-733: A different model with fractions of the heredity coming from each ancestral composing an infinite series. He called this the theory of " Law of Ancestral Heredity ". His ideas were strongly disagreed by William Bateson , who followed Mendel's conclusions, that genetic inheritance were exclusively from the parents, half from each of them. This led to a vigorous debate between the biometricians, who supported Galton's ideas, as Raphael Weldon , Arthur Dukinfield Darbishire and Karl Pearson , and Mendelians, who supported Bateson's (and Mendel's) ideas, such as Charles Davenport and Wilhelm Johannsen . Later, biometricians could not reproduce Galton conclusions in different experiments, and Mendel's ideas prevailed. By

560-406: A drug demonstrates a health benefit over a placebo or other intervention when tested in an ideal situation, such as a tightly controlled clinical trial." These studies focus on a primary parameter to be shown statistically different between placebo and intervention groups. Comparisons of this type are called 'explanatory' randomized controlled trials , whereas 'pragmatic' trials are used to establish

630-400: A drug to have an effect, it needs to bind to its target, and then to affect the function of this target. The target of a drug is commonly referred to as a receptor , but can in general be any chemically sensitive site on any molecule found in the body. The nature of such binding can be quantified by characterising how tightly these molecules, the drug and its receptor, interact: this is known as

700-436: A human-based only method for data collection. Finally, all data collected of interest must be stored in an organized data frame for further analysis. Data can be represented through tables or graphical representation, such as line charts, bar charts, histograms, scatter plot. Also, measures of central tendency and variability can be very useful to describe an overview of the data. Follow some examples: One type of table

770-408: A permanent knowledge about the topic or an obvious occurrence of the phenomena, sustained by a deep literature review. We can say it is the standard expected answer for the data under the situation in test . In general, H O assumes no association between treatments. On the other hand, the alternative hypothesis is the denial of H O . It assumes some degree of association between the treatment and

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840-423: A study aims to understand an effect of a phenomenon over a population . In biology , a population is defined as all the individuals of a given species , in a specific area at a given time. In biostatistics, this concept is extended to a variety of collections possible of study. Although, in biostatistics, a population is not only the individuals, but the total of one specific component of their organisms , as

910-469: A sum, a subtraction must be applied. When testing a hypothesis, there are two types of statistic errors possible: Type I error and Type II error . The significance level denoted by α is the type I error rate and should be chosen before performing the test. The type II error rate is denoted by β and statistical power of the test is 1 − β. The p-value is the probability of obtaining results as extreme as or more extreme than those observed, assuming

980-412: Is a range of values that can contain the true real parameter value in given a certain level of confidence. The first step is to estimate the best-unbiased estimate of the population parameter. The upper value of the interval is obtained by the sum of this estimate with the multiplication between the standard error of the mean and the confidence level. The calculation of lower value is similar, but instead of

1050-591: Is common to use randomized controlled clinical trials , where results are usually compared with observational study designs such as case–control or cohort . Data collection methods must be considered in research planning, because it highly influences the sample size and experimental design. Data collection varies according to type of data. For qualitative data , collection can be done with structured questionnaires or by observation, considering presence or intensity of disease, using score criterion to categorize levels of occurrence. For quantitative data , collection

1120-477: Is commonly achieved by using a more stringent threshold to reject null hypotheses. The Bonferroni correction defines an acceptable global significance level, denoted by α* and each test is individually compared with a value of α = α*/m. This ensures that the familywise error rate in all m tests, is less than or equal to α*. When m is large, the Bonferroni correction may be overly conservative. An alternative to

1190-558: Is done by measuring numerical information using instruments. In agriculture and biology studies, yield data and its components can be obtained by metric measures . However, pest and disease injuries in plats are obtained by observation, considering score scales for levels of damage. Especially, in genetic studies, modern methods for data collection in field and laboratory should be considered, as high-throughput platforms for phenotyping and genotyping. These tools allow bigger experiments, while turn possible evaluate many plots in lower time than

1260-408: Is essential to carry the study based on the three basic principles of experimental statistics: randomization , replication , and local control. The research question will define the objective of a study. The research will be headed by the question, so it needs to be concise, at the same time it is focused on interesting and novel topics that may improve science and knowledge and that field. To define

1330-498: Is not a dead letter, but rather, the power of the Holy Spirit is inherent in it and that Scripture does not compel a mere intellectual assent to its doctrine, resting on logical argumentation, but rather it creates the living agreement of faith . The Smalcald Articles affirm, "in those things which concern the spoken, outward Word , we must firmly hold that God grants His Spirit or grace to no one, except through or with

1400-437: Is often accompanied by other technical assumptions (e.g., about the form of the probability distribution of the outcomes) that are also part of the null hypothesis. When the technical assumptions are violated in practice, then the null may be frequently rejected even if the main hypothesis is true. Such rejections are said to be due to model mis-specification. Verifying whether the outcome of a statistical test does not change when

1470-469: Is proposed to answer a scientific question we might have. To answer this question with a high certainty, we need accurate results. The correct definition of the main hypothesis and the research plan will reduce errors while taking a decision in understanding a phenomenon. The research plan might include the research question, the hypothesis to be tested, the experimental design , data collection methods, data analysis perspectives and costs involved. It

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1540-422: Is required to separate the signal from the noise. For example, a microarray could be used to measure many thousands of genes simultaneously, determining which of them have different expression in diseased cells compared to normal cells. However, only a fraction of genes will be differentially expressed. Multicollinearity often occurs in high-throughput biostatistical settings. Due to high intercorrelation between

1610-410: Is still known as the "Jellinek curve". In post-war 1946, various pharmaceutical chemicals were in short supply for making medicines. A headache remedy manufacturer found that supplies of one of its remedy’s three constituent chemicals was running out. They asked Jellinek, then at Yale, to test whether the absence of that particular chemical would affect the drug’s efficacy in any way. Jellinek set up

1680-501: Is that it is more robust: It is more likely that a single gene is found to be falsely perturbed than it is that a whole pathway is falsely perturbed. Furthermore, one can integrate the accumulated knowledge about biochemical pathways (like the JAK-STAT signaling pathway ) using this approach. The development of biological databases enables storage and management of biological data with the possibility of ensuring access for users around

1750-668: Is the Arabidopsis thaliana genetic and molecular database – TAIR. Phytozome, in turn, stores the assemblies and annotation files of dozen of plant genomes, also containing visualization and analysis tools. Moreover, there is an interconnection between some databases in the information exchange/sharing and a major initiative was the International Nucleotide Sequence Database Collaboration (INSDC) which relates data from DDBJ, EMBL-EBI, and NCBI. Efficacy Efficacy

1820-461: Is the frequency table, which consists of data arranged in rows and columns, where the frequency is the number of occurrences or repetitions of data. Frequency can be: Absolute : represents the number of times that a determined value appear; N = f 1 + f 2 + f 3 + . . . + f n {\displaystyle N=f_{1}+f_{2}+f_{3}+...+f_{n}} Relative : obtained by

1890-437: Is the ability to perform a task to a satisfactory or expected degree. The word comes from the same roots as effectiveness , and it has often been used synonymously, although in pharmacology a distinction is now often made between efficacy and effectiveness . The word efficacy is used in pharmacology and medicine to refer both to the maximum response achievable from a pharmaceutical drug in research settings, and to

1960-590: Is used to describe whether a pesticide is effective in controlling a pest or disease. In Protestant Theology (esp. in Lutheran but also in Calvinist doctrine) efficacy is an attribute of Scripture . The efficacy of Scripture means that it is united with the power of the Holy Spirit and with it, not only demands, but also creates the acceptance of its teaching and that this teaching produces faith and obedience . Efficacy further means that Holy Scripture

2030-518: The Friden calculator from his department at Caltech , saying "Well, I am like a guy who is prospecting for gold along the banks of the Sacramento River in 1849. With a little intelligence, I can reach down and pick up big nuggets of gold. And as long as I can do that, I'm not going to let any people in my department waste scarce resources in placer mining ." Any research in life sciences

2100-771: The WHO 's Expert Committee on Mental Health . The Second Report of the Alcoholism Subcommittee, published in August 1952, have reproduced in its 2nd Annex, the text of an important communication that Jellinek gave to the first European Seminar on Alcoholism in Copenhagen in October 1951. In that conference, he exposed his work on the Phases of alcoholic addiction and he presented a detailed Chart (page 30) exposing

2170-463: The affinity . Efficacy, on the other hand, is a measure of the action of a drug once binding has occurred. The maximum response, E max , will be reduced if efficacy is sufficiently low. The definition of efficacy has been object for discussion. The only way in which absolute measures of efficacy have been obtained is by single ion channel analysis of ligand gated ion channels. It is still not possible to do this for G protein-linked receptors. In

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2240-448: The alternative hypothesis would be that the diets have different effects over animals metabolism (H 1 : μ 1 ≠ μ 2 ). The hypothesis is defined by the researcher, according to his/her interests in answering the main question. Besides that, the alternative hypothesis can be more than one hypothesis. It can assume not only differences across observed parameters, but their degree of differences ( i.e. higher or shorter). Usually,

2310-470: The effectiveness of an intervention regarding also non-specific parameters. Effectiveness refers to "how the drug works in a real-world situation", and is "often lower than efficacy because of interactions with other medications or health conditions of the patient, sufficient dose or duration of use not prescribed by the physician or followed by the patient, or use for an off-label condition that had not been tested." In agriculture and forestry, efficacy

2380-452: The experiment . They are completely randomized design , randomized block design , and factorial designs . Treatments can be arranged in many ways inside the experiment. In agriculture , the correct experimental design is the root of a good study and the arrangement of treatments within the study is essential because environment largely affects the plots ( plants , livestock , microorganisms ). These main arrangements can be found in

2450-485: The null hypothesis (H 0 ) is true. It is also called the calculated probability. It is common to confuse the p-value with the significance level (α) , but, the α is a predefined threshold for calling significant results. If p is less than α, the null hypothesis (H 0 ) is rejected. In multiple tests of the same hypothesis, the probability of the occurrence of falses positives (familywise error rate) increase and some strategy are used to control this occurrence. This

2520-614: The 1920s, he conducted research in Sierra Leone and at Tela , Honduras . In the 1930s he returned to the U.S.A. and worked at the Worcester State Hospital, Worcester, Massachusetts , from whence he was commissioned to conduct a study for the Research Council on Problems of Alcohol . The eventual outcome of his study was the 1942 book, Alcohol Addiction and Chronic Alcoholism . From 1941 to 1952, he

2590-602: The 1930s, models built on statistical reasoning had helped to resolve these differences and to produce the neo-Darwinian modern evolutionary synthesis . Solving these differences also allowed to define the concept of population genetics and brought together genetics and evolution. The three leading figures in the establishment of population genetics and this synthesis all relied on statistics and developed its use in biology. These and other biostatisticians, mathematical biologists , and statistically inclined geneticists helped bring together evolutionary biology and genetics into

2660-571: The Bonferroni correction is to control the false discovery rate (FDR) . The FDR controls the expected proportion of the rejected null hypotheses (the so-called discoveries) that are false (incorrect rejections). This procedure ensures that, for independent tests, the false discovery rate is at most q*. Thus, the FDR is less conservative than the Bonferroni correction and have more power, at the cost of more false positives. The main hypothesis being tested (e.g., no association between treatments and outcomes)

2730-560: The ability to collect data on a high-throughput scale, and the ability to perform much more complex analysis using computational techniques. This comes from the development in areas as sequencing technologies, Bioinformatics and Machine learning ( Machine learning in bioinformatics ). New biomedical technologies like microarrays , next-generation sequencers (for genomics) and mass spectrometry (for proteomics) generate enormous amounts of data, allowing many tests to be performed simultaneously. Careful analysis with biostatistical methods

2800-452: The capacity for sufficient therapeutic effect or beneficial change in clinical settings. In pharmacology, efficacy ( E max ) is the maximum response achievable from an applied or dosed agent, for instance, a small molecule drug. Intrinsic activity is a relative term for a drug's efficacy relative to a drug with the highest observed efficacy. It is a purely descriptive term that has little or no mechanistic interpretation. In order for

2870-423: The case of the glycine receptor and the nicotinic acetylcholine receptor (muscle type), it has been proposed by Sivilotti et al . that opening of the ion channel involves two steps after agonist is bound. Firstly a conformation change to a higher affinity (but still shut) form, followed by the conformation change from shut to open. It was found that partial agonism results from deficiency in the first step, and that

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2940-464: The corresponding residual sum of squares (RSS) and R of the validation test set, not those of the training set. Often, it is useful to pool information from multiple predictors together. For example, Gene Set Enrichment Analysis (GSEA) considers the perturbation of whole (functionally related) gene sets rather than of single genes. These gene sets might be known biochemical pathways or otherwise functionally related genes. The advantage of this approach

3010-529: The data is limited, it is necessary to make use of a representative sample in order to estimate them. With that, it is possible to test previously defined hypotheses and apply the conclusions to the entire population. The standard error of the mean is a measure of variability that is crucial to do inferences. Hypothesis testing is essential to make inferences about populations aiming to answer research questions, as settled in "Research planning" section. Authors defined four steps to be set: A confidence interval

3080-505: The data. Outliers may be plotted as circles. Although correlations between two different kinds of data could be inferred by graphs, such as scatter plot, it is necessary validate this though numerical information. For this reason, correlation coefficients are required. They provide a numerical value that reflects the strength of an association. Pearson correlation coefficient is a measure of association between two variables, X and Y. This coefficient, usually represented by ρ (rho) for

3150-418: The description of gene function classifying it by cellular component, molecular function and biological process ( Gene Ontology ). In addition to databases that contain specific molecular information, there are others that are ample in the sense that they store information about an organism or group of organisms. As an example of a database directed towards just one organism, but that contains much data about it,

3220-440: The development of methods and tools. Gregor Mendel started the genetics studies investigating genetics segregation patterns in families of peas and used statistics to explain the collected data. In the early 1900s, after the rediscovery of Mendel's Mendelian inheritance work, there were gaps in understanding between genetics and evolutionary Darwinism. Francis Galton tried to expand Mendel's discoveries with human data and proposed

3290-430: The disease concept of alcoholism ", and significantly accelerated the movement towards the medicalization of drunkenness and alcohol habituation . Jellinek’s initial 1946 study was funded by Marty Mann and R. Brinkley Smithers (Falcone, 2003). It was based on a narrow, selective study of a hand-picked group of members of Alcoholics Anonymous ( AA ) who had returned a self-reporting questionnaire. Valverde opines that

3360-418: The division of the absolute frequency by the total number; n i = f i N {\displaystyle n_{i}={\frac {f_{i}}{N}}} In the next example, we have the number of genes in ten operons of the same organism. Line graphs represent the variation of a value over another metric, such as time. In general, values are represented in the vertical axis, while

3430-558: The former group as being " reactors to placebo ", and this seems to be the first time that anyone had spoken of either " placebo reactions " or " placebo responses ". The Jellinek Memorial Award , or Jellinek Award , is an award presented annually by the Jellinek Memorial Fund in Jellinek's honor. It is given to a scientist who has made an outstanding contribution to research on alcohol or alcoholism. Winners receive

3500-425: The literature under the names of " lattices ", "incomplete blocks", " split plot ", "augmented blocks", and many others. All of the designs might include control plots , determined by the researcher, to provide an error estimation during inference . In clinical studies , the samples are usually smaller than in other biological studies, and in most cases, the environment effect can be controlled or measured. It

3570-410: The number of items of this collection ( n {\displaystyle {n}} ). The median is the value in the middle of a dataset. The mode is the value of a set of data that appears most often. Box plot is a method for graphically depicting groups of numerical data. The maximum and minimum values are represented by the lines, and the interquartile range (IQR) represent 25–75% of

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3640-532: The number of observations n is smaller than the number of features or predictors p: n < p). As a matter of fact, one can get quite high R -values despite very low predictive power of the statistical model. These classical statistical techniques (esp. least squares linear regression) were developed for low dimensional data (i.e. where the number of observations n is much larger than the number of predictors p: n >> p). In cases of high dimensionality, one should always consider an independent validation test set and

3710-406: The opening and shutting steps are essentially the same for both full and partial agonists. This has been confirmed and extended by Sine and colleagues (2009). The implication of this work is that efficacy has to be defined by at least two equilibrium constants (or, more generally, by four rate constants). The combined influences of affinity and efficacy determine how effectively a drug will produce

3780-481: The outbreak of Zika virus in the birth rate in Brazil. The histogram (or frequency distribution) is a graphical representation of a dataset tabulated and divided into uniform or non-uniform classes. It was first introduced by Karl Pearson . A scatter plot is a mathematical diagram that uses Cartesian coordinates to display values of a dataset. A scatter plot shows the data as a set of points, each one presenting

3850-405: The outcome. Although, the hypothesis is sustained by question research and its expected and unexpected answers. As an example, consider groups of similar animals (mice, for example) under two different diet systems. The research question would be: what is the best diet? In this case, H 0 would be that there is no difference between the two diets in mice metabolism (H 0 : μ 1 = μ 2 ) and

3920-428: The population and r for the sample, assumes values between −1 and 1, where ρ = 1 represents a perfect positive correlation, ρ = −1 represents a perfect negative correlation, and ρ = 0 is no linear correlation. It is used to make inferences about an unknown population, by estimation and/or hypothesis testing. In other words, it is desirable to obtain parameters to describe the population of interest, but since

3990-512: The population. So, the sample might catch the most variability across a population. The sample size is determined by several things, since the scope of the research to the resources available. In clinical research , the trial type, as inferiority , equivalence , and superiority is a key in determining sample size . Experimental designs sustain those basic principles of experimental statistics . There are three basic experimental designs to randomly allocate treatments in all plots of

4060-561: The preceding outward Word." The Formula of Concord teaches that when humans reject the calling of the Holy Spirit, it is not a result of the Word being less efficacious. Instead, contempt for the means of grace is the result of "the perverse will of man, which rejects or perverts the means and instrument of the Holy Ghost, which God offers him through the call , and resists the Holy Ghost, who wishes to be efficacious, and works through

4130-512: The predictors (such as gene expression levels), the information of one predictor might be contained in another one. It could be that only 5% of the predictors are responsible for 90% of the variability of the response. In such a case, one could apply the biostatistical technique of dimension reduction (for example via principal component analysis). Classical statistical techniques like linear or logistic regression and linear discriminant analysis do not work well for high dimensional data (i.e. when

4200-898: The progressive nature of alcoholism. That chart is considered as the 1st version of the future Jellinek's Curve that some other people, including Max Glatt , would eventually draw from his work. Upon his retirement from the WHO in the late 1950s, he returned to the USA. In 1958 he joined the Psychiatry Schools of both the University of Toronto and the University of Alberta , and in 1962, he moved to Stanford University in California, where he remained until his death. Addiction researcher Griffith Edwards (2002, p. 98) holds that, in his opinion, Jellinek's The Disease Concept of Alcoholism

4270-435: The subjects (~60%) responded to the placebo, and 79 did not. The trial also demonstrated that the chemical in question significantly contributed to the remedy's efficacy. In the process of examining the data produced by his trial, Jellinek discovered that there was a significant difference in responses to the active chemicals between the 120 who had responded to the placebo and the 79 who did not. He (1946, p. 90) described

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4340-446: The technical assumptions are slightly altered (so-called robustness checks) is the main way of combating mis-specification. Model criteria selection will select or model that more approximate true model. The Akaike's Information Criterion (AIC) and The Bayesian Information Criterion (BIC) are examples of asymptotically efficient criteria. Recent developments have made a large impact on biostatistics. Two important changes have been

4410-499: The time variation is represented in the horizontal axis. A bar chart is a graph that shows categorical data as bars presenting heights (vertical bar) or widths (horizontal bar) proportional to represent values. Bar charts provide an image that could also be represented in a tabular format. In the bar chart example, we have the birth rate in Brazil for the December months from 2010 to 2016. The sharp fall in December 2016 reflects

4480-466: The value of one variable determining the position on the horizontal axis and another variable on the vertical axis. They are also called scatter graph , scatter chart , scattergram , or scatter diagram . The arithmetic mean is the sum of a collection of values ( x 1 + x 2 + x 3 + ⋯ + x n {\displaystyle {x_{1}+x_{2}+x_{3}+\cdots +x_{n}}} ) divided by

4550-399: The way to ask the scientific question , an exhaustive literature review might be necessary. So the research can be useful to add value to the scientific community . Once the aim of the study is defined, the possible answers to the research question can be proposed, transforming this question into a hypothesis . The main propose is called null hypothesis (H 0 ) and is usually based on

4620-404: The whole genome , or all the sperm cells , for animals, or the total leaf area, for a plant, for example. It is not possible to take the measures from all the elements of a population . Because of that, the sampling process is very important for statistical inference . Sampling is defined as to randomly get a representative part of the entire population, to make posterior inferences about

4690-464: The world. They are useful for researchers depositing data, retrieve information and files (raw or processed) originated from other experiments or indexing scientific articles, as PubMed . Another possibility is search for the desired term (a gene, a protein, a disease, an organism, and so on) and check all results related to this search. There are databases dedicated to SNPs ( dbSNP ), the knowledge on genes characterization and their pathways ( KEGG ) and

4760-661: Was Associate Professor of Applied Physiology at Yale University . In 1941 he was managing editor of the newly established Quarterly Journal of Studies on Alcohol (now the Journal of Studies on Alcohol and Drugs ). In 1950 he was engaged by the World Health Organization in Geneva as a consultant on alcoholism, and made significant contributions to the work of the Alcoholism Sub-committee of

4830-454: Was a work of outstanding scholarship based on a careful consideration of the available evidence. In 1849, the Swedish physician Magnus Huss (1807–1890) was the first to systematically classify the damage that was attributable to alcohol ingestion. Huss coined the term alcoholism and used it to label what he considered to be a chronic, relapsing disease. Jellinek coined the expression "

4900-767: Was born in New York City and died at the desk of his study at Stanford University on 22 October 1963. Jellinek studied biostatistics and physiology at the University of Berlin from 1908 to 1910. He then studied philosophy , philology , anthropology , and theology for two years at the Joseph Fourier University in Grenoble . He was also enrolled, apparently concurrently, at the University of Leipzig from 25 November 1911 to 29 July 1913, and from 22 November 1913 to 2 December 1914 for classes in languages, linguistics and cultural history. During

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