Publications by authors named "Jean M Davidson"

26 Publications

  • Page 1 of 1

Reducing variability of breast cancer subtype predictors by grounding deep learning models in prior knowledge.

Comput Biol Med 2021 11 10;138:104850. Epub 2021 Sep 10.

Department of Biology, California Polytechnic State University, San Luis Obispo, CA, USA. Electronic address:

Deep learning neural networks have improved performance in many cancer informatics problems, including breast cancer subtype classification. However, many networks experience underspecificationwheremultiplecombinationsofparametersachievesimilarperformance, bothin training and validation. Additionally, certain parameter combinations may perform poorly when the test distribution differs from the training distribution. Embedding prior knowledge from the literature may address this issue by boosting predictive models that provide crucial, in-depth information about a given disease. Breast cancer research provides a wealth of such knowledge, particularly in the form of subtype biomarkers and genetic signatures. In this study, we draw on past research on breast cancer subtype biomarkers, label propagation, and neural graph machines to present a novel methodology for embedding knowledge into machine learning systems. We embed prior knowledge into the loss function in the form of inter-subject distances derived from a well-known published breast cancer signature. Our results show that this methodology reduces predictor variability on state-of-the-art deep learning architectures and increases predictor consistency leading to improved interpretation. We find that pathway enrichment analysis is more consistent after embedding knowledge. This novel method applies to a broad range of existing studies and predictive models. Our method moves the traditional synthesis of predictive models from an arbitrary assignment of weights to genes toward a more biologically meaningful approach of incorporating knowledge.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104850DOI Listing
November 2021

An atlas of dynamic chromatin landscapes in mouse fetal development.

Nature 2020 07 29;583(7818):744-751. Epub 2020 Jul 29.

Center for Epigenomics, University of California, San Diego School of Medicine, La Jolla, CA, USA.

The Encyclopedia of DNA Elements (ENCODE) project has established a genomic resource for mammalian development, profiling a diverse panel of mouse tissues at 8 developmental stages from 10.5 days after conception until birth, including transcriptomes, methylomes and chromatin states. Here we systematically examined the state and accessibility of chromatin in the developing mouse fetus. In total we performed 1,128 chromatin immunoprecipitation with sequencing (ChIP-seq) assays for histone modifications and 132 assay for transposase-accessible chromatin using sequencing (ATAC-seq) assays for chromatin accessibility across 72 distinct tissue-stages. We used integrative analysis to develop a unified set of chromatin state annotations, infer the identities of dynamic enhancers and key transcriptional regulators, and characterize the relationship between chromatin state and accessibility during developmental gene regulation. We also leveraged these data to link enhancers to putative target genes and demonstrate tissue-specific enrichments of sequence variants associated with disease in humans. The mouse ENCODE data sets provide a compendium of resources for biomedical researchers and achieve, to our knowledge, the most comprehensive view of chromatin dynamics during mammalian fetal development to date.
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http://dx.doi.org/10.1038/s41586-020-2093-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398618PMC
July 2020

Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts.

Nat Med 2019 06 3;25(6):911-919. Epub 2019 Jun 3.

Department of Computer Science, Stanford University, Stanford, CA, USA.

It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene. The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches. For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases. This includes muscle biopsies from patients with undiagnosed rare muscle disorders, and cultured fibroblasts from patients with mitochondrial disorders. However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
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http://dx.doi.org/10.1038/s41591-019-0457-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6634302PMC
June 2019

Biallelic Mutations in ATP5F1D, which Encodes a Subunit of ATP Synthase, Cause a Metabolic Disorder.

Am J Hum Genet 2018 03 22;102(3):494-504. Epub 2018 Feb 22.

Department of Pediatrics, Paracelsus Medical University, 5020 Salzburg, Austria.

ATP synthase, H transporting, mitochondrial F1 complex, δ subunit (ATP5F1D; formerly ATP5D) is a subunit of mitochondrial ATP synthase and plays an important role in coupling proton translocation and ATP production. Here, we describe two individuals, each with homozygous missense variants in ATP5F1D, who presented with episodic lethargy, metabolic acidosis, 3-methylglutaconic aciduria, and hyperammonemia. Subject 1, homozygous for c.245C>T (p.Pro82Leu), presented with recurrent metabolic decompensation starting in the neonatal period, and subject 2, homozygous for c.317T>G (p.Val106Gly), presented with acute encephalopathy in childhood. Cultured skin fibroblasts from these individuals exhibited impaired assembly of FF ATP synthase and subsequent reduced complex V activity. Cells from subject 1 also exhibited a significant decrease in mitochondrial cristae. Knockdown of Drosophila ATPsynδ, the ATP5F1D homolog, in developing eyes and brains caused a near complete loss of the fly head, a phenotype that was fully rescued by wild-type human ATP5F1D. In contrast, expression of the ATP5F1D c.245C>T and c.317T>G variants rescued the head-size phenotype but recapitulated the eye and antennae defects seen in other genetic models of mitochondrial oxidative phosphorylation deficiency. Our data establish c.245C>T (p.Pro82Leu) and c.317T>G (p.Val106Gly) in ATP5F1D as pathogenic variants leading to a Mendelian mitochondrial disease featuring episodic metabolic decompensation.
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http://dx.doi.org/10.1016/j.ajhg.2018.01.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117612PMC
March 2018

The Encyclopedia of DNA elements (ENCODE): data portal update.

Nucleic Acids Res 2018 01;46(D1):D794-D801

Department of Genetics, Stanford University, Stanford, CA 94305-5120, USA.

The Encyclopedia of DNA Elements (ENCODE) Data Coordinating Center has developed the ENCODE Portal database and website as the source for the data and metadata generated by the ENCODE Consortium. Two principles have motivated the design. First, experimental protocols, analytical procedures and the data themselves should be made publicly accessible through a coherent, web-based search and download interface. Second, the same interface should serve carefully curated metadata that record the provenance of the data and justify its interpretation in biological terms. Since its initial release in 2013 and in response to recommendations from consortium members and the wider community of scientists who use the Portal to access ENCODE data, the Portal has been regularly updated to better reflect these design principles. Here we report on these updates, including results from new experiments, uniformly-processed data from other projects, new visualization tools and more comprehensive metadata to describe experiments and analyses. Additionally, the Portal is now home to meta(data) from related projects including Genomics of Gene Regulation, Roadmap Epigenome Project, Model organism ENCODE (modENCODE) and modERN. The Portal now makes available over 13000 datasets and their accompanying metadata and can be accessed at: https://www.encodeproject.org/.
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http://dx.doi.org/10.1093/nar/gkx1081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5753278PMC
January 2018

SnoVault and encodeD: A novel object-based storage system and applications to ENCODE metadata.

PLoS One 2017 12;12(4):e0175310. Epub 2017 Apr 12.

Stanford University School of Medicine, Department of Genetics, Stanford, California, United States of America.

The Encyclopedia of DNA elements (ENCODE) project is an ongoing collaborative effort to create a comprehensive catalog of functional elements initiated shortly after the completion of the Human Genome Project. The current database exceeds 6500 experiments across more than 450 cell lines and tissues using a wide array of experimental techniques to study the chromatin structure, regulatory and transcriptional landscape of the H. sapiens and M. musculus genomes. All ENCODE experimental data, metadata, and associated computational analyses are submitted to the ENCODE Data Coordination Center (DCC) for validation, tracking, storage, unified processing, and distribution to community resources and the scientific community. As the volume of data increases, the identification and organization of experimental details becomes increasingly intricate and demands careful curation. The ENCODE DCC has created a general purpose software system, known as SnoVault, that supports metadata and file submission, a database used for metadata storage, web pages for displaying the metadata and a robust API for querying the metadata. The software is fully open-source, code and installation instructions can be found at: http://github.com/ENCODE-DCC/snovault/ (for the generic database) and http://github.com/ENCODE-DCC/encoded/ to store genomic data in the manner of ENCODE. The core database engine, SnoVault (which is completely independent of ENCODE, genomic data, or bioinformatic data) has been released as a separate Python package.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0175310PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389787PMC
April 2017

Resources for the Comprehensive Discovery of Functional RNA Elements.

Mol Cell 2016 Mar;61(6):903-13

Department of Cellular and Molecular Medicine, Institute for Genomic Medicine, Stem Cell Program, Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA 92037, USA. Electronic address:

Transcriptome-wide maps of RNA binding protein (RBP)-RNA interactions by immunoprecipitation (IP)-based methods such as RNA IP (RIP) and crosslinking and IP (CLIP) are key starting points for evaluating the molecular roles of the thousands of human RBPs. A significant bottleneck to the application of these methods in diverse cell lines, tissues, and developmental stages is the availability of validated IP-quality antibodies. Using IP followed by immunoblot assays, we have developed a validated repository of 438 commercially available antibodies that interrogate 365 unique RBPs. In parallel, 362 short-hairpin RNA (shRNA) constructs against 276 unique RBPs were also used to confirm specificity of these antibodies. These antibodies can characterize subcellular RBP localization. With the burgeoning interest in the roles of RBPs in cancer, neurobiology, and development, these resources are invaluable to the broad scientific community. Detailed information about these resources is publicly available at the ENCODE portal (https://www.encodeproject.org/).
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http://dx.doi.org/10.1016/j.molcel.2016.02.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839293PMC
March 2016

Principles of metadata organization at the ENCODE data coordination center.

Database (Oxford) 2016 15;2016. Epub 2016 Mar 15.

Department of Genetics, Stanford University School of Medicine Department of Genetics, Stanford, CA, USA

The Encyclopedia of DNA Elements (ENCODE) Data Coordinating Center (DCC) is responsible for organizing, describing and providing access to the diverse data generated by the ENCODE project. The description of these data, known as metadata, includes the biological sample used as input, the protocols and assays performed on these samples, the data files generated from the results and the computational methods used to analyze the data. Here, we outline the principles and philosophy used to define the ENCODE metadata in order to create a metadata standard that can be applied to diverse assays and multiple genomic projects. In addition, we present how the data are validated and used by the ENCODE DCC in creating the ENCODE Portal (https://www.encodeproject.org/). Database URL: www.encodeproject.org.
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http://dx.doi.org/10.1093/database/baw001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792520PMC
October 2016

Integrative Genomics Implicates EGFR as a Downstream Mediator in NKX2-1 Amplified Non-Small Cell Lung Cancer.

PLoS One 2015 10;10(11):e0142061. Epub 2015 Nov 10.

Department of Pathology, Stanford University School of Medicine, Stanford, California, United States of America.

NKX2-1, encoding a homeobox transcription factor, is amplified in approximately 15% of non-small cell lung cancers (NSCLC), where it is thought to drive cancer cell proliferation and survival. However, its mechanism of action remains largely unknown. To identify relevant downstream transcriptional targets, here we carried out a combined NKX2-1 transcriptome (NKX2-1 knockdown followed by RNAseq) and cistrome (NKX2-1 binding sites by ChIPseq) analysis in four NKX2-1-amplified human NSCLC cell lines. While NKX2-1 regulated genes differed among the four cell lines assayed, cell proliferation emerged as a common theme. Moreover, in 3 of the 4 cell lines, epidermal growth factor receptor (EGFR) was among the top NKX2-1 upregulated targets, which we confirmed at the protein level by western blot. Interestingly, EGFR knockdown led to upregulation of NKX2-1, suggesting a negative feedback loop. Consistent with this finding, combined knockdown of NKX2-1 and EGFR in NCI-H1819 lung cancer cells reduced cell proliferation (as well as MAP-kinase and PI3-kinase signaling) more than knockdown of either alone. Likewise, NKX2-1 knockdown enhanced the growth-inhibitory effect of the EGFR-inhibitor erlotinib. Taken together, our findings implicate EGFR as a downstream effector of NKX2-1 in NKX2-1 amplified NSCLC, with possible clinical implications, and provide a rich dataset for investigating additional mediators of NKX2-1 driven oncogenesis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0142061PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4640868PMC
June 2016

ENCODE data at the ENCODE portal.

Nucleic Acids Res 2016 Jan 2;44(D1):D726-32. Epub 2015 Nov 2.

Stanford University School of Medicine, Department of Genetics, Stanford, CA, 94305, USA

The Encyclopedia of DNA Elements (ENCODE) Project is in its third phase of creating a comprehensive catalog of functional elements in the human genome. This phase of the project includes an expansion of assays that measure diverse RNA populations, identify proteins that interact with RNA and DNA, probe regions of DNA hypersensitivity, and measure levels of DNA methylation in a wide range of cell and tissue types to identify putative regulatory elements. To date, results for almost 5000 experiments have been released for use by the scientific community. These data are available for searching, visualization and download at the new ENCODE Portal (www.encodeproject.org). The revamped ENCODE Portal provides new ways to browse and search the ENCODE data based on the metadata that describe the assays as well as summaries of the assays that focus on data provenance. In addition, it is a flexible platform that allows integration of genomic data from multiple projects. The portal experience was designed to improve access to ENCODE data by relying on metadata that allow reusability and reproducibility of the experiments.
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http://dx.doi.org/10.1093/nar/gkv1160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702836PMC
January 2016

Ontology application and use at the ENCODE DCC.

Database (Oxford) 2015 16;2015. Epub 2015 Mar 16.

Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA and Center for Biomolecular Science and Engineering, School of Engineering, University of California Santa Cruz, Santa Cruz, CA 95064, USA

The Encyclopedia of DNA elements (ENCODE) project is an ongoing collaborative effort to create a catalog of genomic annotations. To date, the project has generated over 4000 experiments across more than 350 cell lines and tissues using a wide array of experimental techniques to study the chromatin structure, regulatory network and transcriptional landscape of the Homo sapiens and Mus musculus genomes. All ENCODE experimental data, metadata and associated computational analyses are submitted to the ENCODE Data Coordination Center (DCC) for validation, tracking, storage and distribution to community resources and the scientific community. As the volume of data increases, the organization of experimental details becomes increasingly complicated and demands careful curation to identify related experiments. Here, we describe the ENCODE DCC's use of ontologies to standardize experimental metadata. We discuss how ontologies, when used to annotate metadata, provide improved searching capabilities and facilitate the ability to find connections within a set of experiments. Additionally, we provide examples of how ontologies are used to annotate ENCODE metadata and how the annotations can be identified via ontology-driven searches at the ENCODE portal. As genomic datasets grow larger and more interconnected, standardization of metadata becomes increasingly vital to allow for exploration and comparison of data between different scientific projects.
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http://dx.doi.org/10.1093/database/bav010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4360730PMC
September 2015

Doctors' age at domestic partnership and parenthood: cohort studies.

J R Soc Med 2012 Sep;105(9):390-9

UK Medical Careers Research Group, Unit of Healthcare Epidemiology, Department of Public Health, Oxford University, UK.

Objective: To report on doctors' family formation. Design Cohort studies using structured questionnaires. Setting UK. Participants Doctors who qualified in 1988, 1993, 1996, 1999, 2000 and 2002 were followed up.

Main Outcome Measures: Living with spouse or partner; and doctors' age when first child was born.

Results: The response to surveys including questions about domestic circumstances was 89.8% (20,717/23,077 doctors). The main outcomes - living with spouse or partner, and parenthood - varied according to age at qualification. Using the modal ages of 23-24 years at qualification, by the age of 24-25 (i.e. in their first year of medical work) a much smaller percentage of doctors than the general population was living with spouse or partner. By the age of 33, 75% of both women and men doctors were living with spouse or partner, compared with 68% of women and 61% of men aged 33 in the general population. By the age of 24-25, 2% of women doctors and 41% of women in the general population had a child; but women doctors caught up with the general population, in this respect, in their 30s. The specialty with the highest percentage of women doctors who, aged 35, had children was general practice (74%); the lowest was surgery (41%).

Conclusions: Doctors are more likely than other people to live with a spouse or partner, and to have children, albeit typically at later ages. Differences between specialties in rates of motherhood may indicate sacrifice by some women of family in favour of career.
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http://dx.doi.org/10.1258/jrsm.2012.120016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3439659PMC
September 2012

S phase-coupled E2f1 destruction ensures homeostasis in proliferating tissues.

PLoS Genet 2012 16;8(8):e1002831. Epub 2012 Aug 16.

Department of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.

Precise control of cell cycle regulators is critical for normal development and tissue homeostasis. E2F transcription factors are activated during G1 to drive the G1-S transition and are then inhibited during S phase by a variety of mechanisms. Here, we genetically manipulate the single Drosophila activator E2F (E2f1) to explore the developmental requirement for S phase-coupled E2F down-regulation. Expression of an E2f1 mutant that is not destroyed during S phase drives cell cycle progression and causes apoptosis. Interestingly, this apoptosis is not exclusively the result of inappropriate cell cycle progression, because a stable E2f1 mutant that cannot function as a transcription factor or drive cell cycle progression also triggers apoptosis. This observation suggests that the inappropriate presence of E2f1 protein during S phase can trigger apoptosis by mechanisms that are independent of E2F acting directly at target genes. The ability of S phase-stabilized E2f1 to trigger apoptosis requires an interaction between E2f1 and the Drosophila pRb homolog, Rbf1, and involves induction of the pro-apoptotic gene, hid. Simultaneously blocking E2f1 destruction during S phase and inhibiting the induction of apoptosis results in tissue overgrowth and lethality. We propose that inappropriate accumulation of E2f1 protein during S phase triggers the elimination of potentially hyperplastic cells via apoptosis in order to ensure normal development of rapidly proliferating tissues.
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http://dx.doi.org/10.1371/journal.pgen.1002831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3420931PMC
December 2012

Using Drosophila S2 cells to measure S phase-coupled protein destruction via flow cytometry.

Methods Mol Biol 2011 ;782:205-19

Department of Biology, University of North Carolina, Chapel Hill, NC, USA.

Cell proliferation depends on the timely synthesis and destruction of proteins at specific phases of the cell cycle. Recently it was discovered that the destruction of several key cell cycle regulatory proteins during S phase is coupled directly to DNA replication. These proteins harbor a motif called a PIP degron that mediates binding to chromatin bound PCNA at replication forks and recruits the CRL4(Cdt2) E3 ubiquitin ligase. These interactions comprise an elegant mechanism for coupling DNA replication with ubiquitylation and subsequent proteolysis by the 26S proteasome. Here we describe a flow cytometry-based method using Drosophila S2 cells that recapitulates S phase-specific protein proteolysis. Because of the high degree of evolutionary conservation of the PIP degron and CRL4(Cdt2) and the ease of culturing and inhibiting gene function by RNAi in S2 cells, our flow cytometric method should serve as a general tool for determining whether any eukaryotic protein is subject to replication-coupled protein destruction.
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http://dx.doi.org/10.1007/978-1-61779-273-1_15DOI Listing
January 2012

Loss of the histone pre-mRNA processing factor stem-loop binding protein in Drosophila causes genomic instability and impaired cellular proliferation.

PLoS One 2009 Dec 4;4(12):e8168. Epub 2009 Dec 4.

Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina, United States of America.

Background: Metazoan replication-dependent histone mRNAs terminate in a conserved stem-loop structure rather than a polyA tail. Formation of this unique mRNA 3' end requires Stem-loop Binding Protein (SLBP), which directly binds histone pre-mRNA and stimulates 3' end processing. The 3' end stem-loop is necessary for all aspects of histone mRNA metabolism, including replication coupling, but its importance to organism fitness and genome maintenance in vivo have not been characterized.

Methodology/principal Findings: In Drosophila, disruption of the Slbp gene prevents normal histone pre-mRNA processing and causes histone pre-mRNAs to utilize the canonical 3' end processing pathway, resulting in polyadenylated histone mRNAs that are no longer properly regulated. Here we show that Slbp mutants display genomic instability, including loss of heterozygosity (LOH), increased presence of chromosome breaks, tetraploidy, and changes in position effect variegation (PEV). During imaginal disc growth, Slbp mutant cells show defects in S phase and proliferate more slowly than control cells.

Conclusions/significance: These data are consistent with a model in which changing the 3' end of histone mRNA disrupts normal replication-coupled histone mRNA biosynthesis and alters chromatin assembly, resulting in genomic instability, inhibition of cell proliferation, and impaired development.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0008168PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2781718PMC
December 2009

Endoreplication: polyploidy with purpose.

Genes Dev 2009 Nov;23(21):2461-77

Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.

A great many cell types are necessary for the myriad capabilities of complex, multicellular organisms. One interesting aspect of this diversity of cell type is that many cells in diploid organisms are polyploid. This is called endopolyploidy and arises from cell cycles that are often characterized as "variant," but in fact are widespread throughout nature. Endopolyploidy is essential for normal development and physiology in many different organisms. Here we review how both plants and animals use variations of the cell cycle, termed collectively as endoreplication, resulting in polyploid cells that support specific aspects of development. In addition, we discuss briefly how endoreplication occurs in response to certain physiological stresses, and how it may contribute to the development of cancer. Finally, we describe the molecular mechanisms that support the onset and progression of endoreplication.
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http://dx.doi.org/10.1101/gad.1829209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2779750PMC
November 2009

Retention in the British National Health Service of medical graduates trained in Britain: cohort studies.

BMJ 2009 Jun 3;338:b1977. Epub 2009 Jun 3.

UK Medical Careers Research Group, Department of Public Health, University of Oxford, Old Road Campus, Oxford OX3 7LF.

Objective: To report the percentage of graduates from British medical schools who eventually practise medicine in the British NHS.

Design: Cohort studies using postal questionnaires, employment data, and capture-recapture analysis.

Setting: Great Britain.

Subjects: 32 430 graduates from all British medical schools in nine graduation cohorts from 1974 to 2002, subdivided into home based medical students (those whose homes were in Great Britain when they entered medical school) and those from overseas (whose homes were outside Great Britain when they entered medical school).

Main Outcome Measures: Working in the NHS at seven census points from two to 27 years after qualification.

Results: Of home based doctors, 88% of men (6807 of 7754) and 88% of women (7909 of 8985) worked as doctors in the NHS two years after qualification. The corresponding values were 87% of men (7483 of 8646) and 86% of women (7364 of 8594) at five years; 86% (6803 of 7872) and 86% (5407 of 6321) at 10 years; 85% (5404 of 6331) and 84% (3206 of 3820) at 15 years; and 82% (2534 of 3089) and 81% (1132 of 1395) at 20 years. Attrition from the NHS had not increased in recent cohorts compared with older ones at similar times after graduation. Of overseas students, 76% (776 of 1020) were in the NHS at two years, 72% (700 of 972) at five years, 63% (448 of 717) at ten years, and 52% (128 of 248) at 20 years.

Conclusions: The majority of British medical graduates from British medical schools practise in the NHS in both the short and long term. Differences between men and women in this respect are negligible. A majority of doctors from overseas homes remain in Britain for their years as junior doctors, but eventually about half leave the NHS.
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http://dx.doi.org/10.1136/bmj.b1977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2690621PMC
June 2009

The first house officer year: views of graduate and non-graduate entrants to medical school.

Med Educ 2008 Mar;42(3):286-93

Department of Public Health, University of Oxford, Oxford, UK.

Objective: To determine whether graduate and non-graduate entrants to medical school differ in their views on the first year spent in medical practice as a pre-registration house officer.

Methods: We carried out postal questionnaire surveys of medical qualifiers of 1999, 2000 and 2002 from all UK medical schools, 1 year after qualification. The timing of the study slightly pre-dates the recent major expansion in graduate entry fast-track courses.

Results: Differences between graduate and non-graduate entrants were few and, even when statistically significant, were small in scale. Graduate entrants viewed their working hours, pay and living conditions at work, such as hospital accommodation and food, a little less favourably than did non-graduate entrants. Graduate entrants were also less satisfied than non-graduates with time available for family, social and recreational activities. However, graduate entrants were more likely than non-graduate entrants to feel positive about their future career prospects. There were no differences between graduate and non-graduate entrants in whether they felt they had been well prepared by their medical schools for the jobs they undertook as house officers. Levels of job satisfaction expressed by graduate and non-graduate entrants were similar, as were their responses to most other statements about attitudes to clinical work.

Conclusions: 'Quality of life' issues, a sense of being fairly rewarded, and expectations about one's physical working environment seem a little more important to graduate than to non-graduate entrants. Apart from these, the findings suggest that graduate status, at entry to medical school, has no appreciable influence on attitudes to the work of a junior hospital doctor.
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http://dx.doi.org/10.1111/j.1365-2923.2007.02992.xDOI Listing
March 2008

Career preferences of graduate and non-graduate entrants to medical schools in the UK.

Med Educ 2007 Apr;41(4):349-61

Department of Public Health, University of Oxford, Oxford, UK.

Objective: Recent UK policy has been to increase substantially the number of graduate entrants to medical schools. Our aim was to study whether graduate and non-graduate entrants have different long-term career preferences.

Methods: We conducted postal questionnaire surveys of medical qualifiers from all UK medical schools in 1999, 2000 and 2002, surveyed 1 year after qualification, and qualifiers of 1999 and 2000, surveyed 3 years after qualification.

Results: By Year 3 after qualification, general practice was the choice of 33% of men graduate entrants and 21% of men non-graduates ( = 12.5, P < 0.001) and of 43% of women graduates and 38% of women non-graduates ( = 1.6, P = 0.2). Surgery was a much less popular choice for men graduate entrants than for men non-graduates; but similar percentages of women graduate and non-graduate entrants chose surgery. A lower percentage of graduate entrants than of non-graduates favoured paediatrics. Other differences between graduates and non-graduates were generally small. General practice was the preferred career for a much lower percentage of those who took an intercalated degree while at medical school, than of those who did not.

Conclusions: Increasing graduate entry to medical school is likely to increase the percentage of doctors who want to become general practitioners, but only modestly so. It may also lead to a decline in the percentages choosing surgery and paediatrics. Otherwise, at least on the current criteria used for selecting students, increasing graduate entry will probably not make much difference to the percentage of newly qualified doctors seeking careers in different branches of practice.
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http://dx.doi.org/10.1111/j.1365-2929.2007.02706.xDOI Listing
April 2007

Country of training and ethnic origin of UK doctors: database and survey studies.

BMJ 2004 Sep 3;329(7466):597. Epub 2004 Sep 3.

UK Medical Careers Research Group, Department of Public Health, University of Oxford, Oxford OX3 7LF.

Objectives: To report on the country of training and ethnicity of consultants in different specialties in the NHS, on trends in intake to UK medical schools by ethnicity, and on the specialty choices made by UK medical graduates in different ethnic groups.

Design: Analysis of official databases of consultants and of students accepted to study medicine; survey data about career choices made by newly qualified doctors.

Setting And Subjects: England and Wales (consultants), United Kingdom (students and newly qualified doctors).

Results: Of consultants appointed before 1992, 15% had trained abroad; of those appointed in 1992-2001, 24% had trained abroad. The percentage of consultants who had trained abroad and were non-white was significantly high, compared with their overall percentage among consultants, in geriatric medicine, genitourinary medicine, paediatrics, old age psychiatry, and learning disability. UK trained non-white doctors had specialty destinations similar to those of UK trained white doctors. The percentage of UK medical graduates who are non-white has increased substantially from about 2% in 1974 and will approach 30% by 2005. White men now comprise little more than a quarter of all UK medical students. White and non-white UK graduates make similar choices of specialty.

Conclusions: Specialist medical practice in the NHS has been heavily dependent on doctors who have trained abroad, particularly in specialties where posts have been hard to fill. By contrast, UK trained doctors from ethnic minorities are not over-represented in the less popular specialties. Ethnic minorities are well represented in UK medical school intakes; and white men, but not white women, are now substantially under-represented.
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http://dx.doi.org/10.1136/bmj.38202.364271.BEDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC516656PMC
September 2004

Doctors' views of their first year of medical work and postgraduate training in the UK: questionnaire surveys.

Med Educ 2003 Sep;37(9):802-8

UK Medical Career Research Group, Unit of Health Care Epidemiology, Department of Public Health, University of Oxford, Old Road, Oxford, UK.

Objective: The first year of postgraduate work for newly qualified doctors in the UK, the pre-registration year, is spent working intensively in training posts under supervision. Our aim was to report the views of pre-registration doctors on these posts.

Design: Questionnaire survey.

Subjects: All medical graduates of 1999 and a 25% sample of graduates of 2000 from all UK medical schools.

Main Outcome Measures: Doctors' views on the pre-registration house officer (PRHO) year, recorded as ratings in answers to questions and statements about the year.

Results: In reply to the question 'How much have you enjoyed the PRHO year overall?', rated on a scale from 0-10 (0 = no enjoyment; 10 = enjoyed it greatly), 44% of respondents (1341/3068) gave scores of 8-10; in all, 83.2% of respondents gave scores in the upper half of the scale (> or =6). However, there were criticisms of specific aspects of working conditions. Only a third agreed that their training during the year had been of a high standard. Posts in medicine were rated more highly than those in surgery for quality of training. Differences in views held by women and men junior doctors were few. However, where differences existed, women were slightly more positive about their work than men.

Conclusion: Most graduates enjoyed the pre-registration year but there is still considerable scope for improvement in working conditions and training. Men and women gave similar responses, which suggests that later divergence in their career pathways is not attributable to different views formed about work in their pre-registration year.
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http://dx.doi.org/10.1046/j.1365-2923.2003.01611.xDOI Listing
September 2003

Doctors' reasons for rejecting initial choices of specialties as long-term careers.

Med Educ 2003 Apr;37(4):312-8

UK Medical Careers Research Group, Unit of Health Care Epidemiology, University of Oxford, UK.

Objectives: To report on rejected choices of specialty as long-term careers and reasons for rejection.

Design: Postal questionnaire survey.

Setting: United Kingdom.

Participants: All graduates of 1996 and 1999 from UK medical schools during their first year after qualification.

Main Outcome Measures: Any career choice which had been seriously considered and rejected and the reason for its rejection.

Results: In all, 33.1% (1871) of respondents named a rejected choice and gave reasons for its rejection. Disproportionately high numbers rejected the surgical specialties, paediatrics and obstetrics and gynaecology (O&G), using the specialty distribution of positive choices as the comparator. Relatively few doctors rejected general practice (GP) after giving it serious consideration. Doctors rejecting the hospital medical and surgical specialties or paediatrics were most likely to specify reasons relating to quality of life. Three-quarters of the graduates of 1999 who rejected O&G did so because of poor career prospects.

Conclusions: Quality of life issues, and concerns about working relationships, are sufficiently influential to persuade many doctors to abandon an initial choice of medical career. It is unlikely that much of the decline in entry to GP is attributable to rejection of GP by doctors who initially chose it. The decline must therefore represent an increase in the number of doctors who had never seriously considered it as a long-term career choice.
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http://dx.doi.org/10.1046/j.1365-2923.2003.01473.xDOI Listing
April 2003

UK senior doctors' career destinations, job satisfaction, and future intentions: questionnaire survey.

BMJ 2002 Sep;325(7366):685-6

UK Medical Careers Research Group, Unit of Health-Care Epidemiology, Department of Public Health, University of Oxford, Oxford OX3 7LF.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC126656PMC
http://dx.doi.org/10.1136/bmj.325.7366.685DOI Listing
September 2002
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