PurposeThe study aimed at widening the clinical and genetic spectrum and assessing genotype-phenotype associations in FOXG1 syndrome due to FOXG1 variants.MethodsWe compiled 30 new and 53 reported patients with a heterozygous pathogenic or likely pathogenic variant in FOXG1. We grouped patients according to type and location of the variant. Statistical analysis of molecular and clinical data was performed using Fisher's exact test and a nonparametric multivariate test.ResultsAmong the 30 new patients, we identified 19 novel FOXG1 variants. Among the total group of 83 patients, there were 54 variants: 20 frameshift (37%), 17 missense (31%), 15 nonsense (28%), and 2 in-frame variants (4%). Frameshift and nonsense variants are distributed over all FOXG1 protein domains; missense variants cluster within the conserved forkhead domain. We found a higher phenotypic variability than previously described. Genotype-phenotype association revealed significant differences in psychomotor development and neurological features between FOXG1 genotype groups. More severe phenotypes were associated with truncating FOXG1 variants in the N-terminal domain and the forkhead domain (except conserved site 1) and milder phenotypes with missense variants in the forkhead conserved site 1.ConclusionsThese data may serve for improved interpretation of new FOXG1 sequence variants and well-founded genetic counseling.

Patients with an interstitial 13q deletion that contains the RB1 gene show retinoblastoma and variable clinical features. Relationship between phenotypic expression and loss of specific neighboring genes are unresolved, yet. We obtained clinical, cytogenetic and molecular data in 63 patients with an interstitial 13q deletion involving RB1. Whole-genome array analysis or customized high-resolution array analysis for 13q14.11q14.3 was performed in 38 patients, and cytogenetic analysis was performed in 54 patients. Deletion sizes ranged between 4.2 kb and more than 33.43 Mb; breakpoints were non-recurrent. Sequence analysis of deletion junctions in five patients revealed microhomology and insertion of 2-34 base pairs suggestive of non-homologous end joining. Milder phenotypic expression of retinoblastoma was observed in patients with deletions larger than 1 Mb, which contained the MED4 gene. Clinical features were compared between patients with small (within 13q14), medium (within 13q12.3q21.2) and large (within 13q12q31.2) deletions. Patients with a small deletion can show macrocephaly, tall stature, obesity, motor and/or speech delay. Patients with a medium deletion show characteristic facial features, mild to moderate psychomotor delay, short stature and microcephaly. Patients with a large deletion have characteristic craniofacial dysmorphism, short stature, microcephaly, mild to severe psychomotor delay, hypotonia, constipation and feeding problems. Additional features included deafness, seizures and brain and heart anomalies. We found no correlation between clinical features and parental origin of the deletion. Our data suggest that hemizygous loss of NUFIP1 and PCDH8 may contribute to psychomotor delay, deletion of MTLR1 to microcephaly and loss of EDNRB to feeding difficulties and deafness.

Purpose -Studying academic careers can be particularly useful for discussions about new forms of professional careers. This conceptual paper seeks to shed light on academic careers by discussing the (changing) multiple contexts governing academic careers. Design/methodology/approach -A neo-institutional framework for analysing academic careers is developed that treats them as outcomes of overlapping institutions belonging to the different social contexts in which academics simultaneously act. This approach allows one to locate academic careers in the context of new and traditional career literature and to address changes in the institutional context of academic careers. Findings -Shows how traditional structures and mechanisms of academic careers are interwoven with the overall patterns of national higher education systems and their societal embeddedness. Empirical evidence was found that academic careers are becoming more boundaryless. But evidence was also found that academic careers are more bound to the organisation due to recent changes in university policies and practices.Research limitations/implications -The paper is limited to the discussion of overlapping institutional contexts governing academic careers. Further international comparisons could deepen understanding of specific formal and informal rules. Future macro-micro research enables one to show how the career models can be traced to the career experiences and practices. Micro-macro research allows one to see how the aggregate outcomes of individual actions can be traced to the overall performance of a given higher education system. Originality/value -This conceptual paper proposes a neo-institutional framework for analysing academic careers. This approach is useful for cross-national comparisons, the study of emerging new career models and practices in academe, and the study of macro-micro-links in career research.

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Purpose – The purpose of this paper is to focus on doctoral students in Germany and the drivers behind their intention to enter an academic career. The aspirations of young researchers after graduating from doctoral training have become an important issue to policymakers in light of the changing nature of doctoral training. Design/methodology/approach – Borrowing from Ajzen’s Theory of Planned Behavior, we investigate how attitudes towards a career in academia, subjective norms and perceived behavioral control determine graduates’ intentions to pursue an academic career. We extend the model of Ajzen by measurements of research and training conditions in order to estimate the impact of organizational settings. We analyze a sample of 5,770 doctoral candidates from eight universities and three funding organizations. Findings – We find that apart from attitudes towards careers, academic career intentions are related to research and training conditions at the organizational level. Further, we find that large differences within the field of study and affiliation to a university or funding organization provide substantial explanations. Originality/value – This paper explores doctoral candidates’ academic career intentions which are an important precondition for the propagation of academic staff. For developers and practitioners in the field of doctoral training, our results yield a good understanding of the relationship between organizational settings at the level of doctoral training and career intentions.

In addition to mutations in both alleles of the retinoblastoma gene (RB1) alleles, retinoblastomas frequently show additional alterations including loss of chromosome arm 16q. In a previous study, the presence of 16q alterations was found to be associated with diffuse vitreous seeding of this tumor. This growth pattern is clinically important as it determines therapeutic decisions. The present study was designed to test this association and to narrow down the list of candidate genes in the minimal region of genomic loss on chromosome arm 16q. Our data confirm the association of 16q loss and diffuse vitreous seeding and define a minimal region of genomic loss of 6.6 Mb on 16q containing 86 known genes. As retinoblastoma is an embryonic tumor, we assumed that any gene relevant for its progression is likely to show regulated expression during retinogenesis. Microarray expression analysis of RNA from a continuous developmental series of murine retinas identified murine orthologs with regulated expression and these data helped to narrow the number of candidate genes in minimal region to 35. Analysis of gene expression in retinoblastomas with and without the loss of heterozygosity (LOH) on chromosome 16q further reduced this number to 26 candidate genes. One of these genes is cadherin 13 (CDH13) and notably, downregulation of CHD13 has previously been associated with poorer prognosis in various other cancers.

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With an ever-increasing amount of data, it is essential for many systems that documents can be retrieved efficiently.The process of information retrieval can be supported by metadata enrichment of the documents. The aim of thiswork is to make scientific publications and project descriptions, consisting of titles, abstracts and bibliographicalreferences, easier to find. Therefore, we investigate text analytical methods such as keyword extraction algorithms(TFIDF, Log-Likelihood, RAKE, TAKE and KECNW) and classification approaches using a SVM withensembles of classifier chains (Web of Science and GEPRIS categories as taxonomies) and compare their quality.We present an altered an optimized keyword extraction algorithm and a supervised subject and keywordclassification approach which are, to our knowledge so far, one of the first automatic applications of this kind ininformetrics and scientific information retrieval.The most promising methods are employed and the extracted information is attached to the documents as metadata.These support a search query, using pseudo relevance feedback, to obtain further relevant search results and canalso be used to derive profiles for authors, faculties, etc. The concepts developed here will serve as a basis for theLeipzig University Research Information System.