Content-based image retrieval (CBIR) has been proposed as key technology for computer-aided diagnostics (CAD). This paper reviews the state of the art and future challenges in CBIR for CAD applied to clinical practice.
We define applicability to clinical practice by having recently demonstrated the CBIR system on one of the CAD demonstration workshops held at international conferences, such as SPIE Medical Imaging, CARS, SIIM, RSNA, and IEEE ISBI. From 2009 to 2011, the programs of CADdemo@CARS and the CAD Demonstration Workshop at SPIE Medical Imaging were sought for the key word “retrieval” in the title. The systems identified were analyzed and compared according to the hierarchy of gaps for CBIR systems.
In total, 70 software demonstrations were analyzed. 5 systems were identified meeting the criterions. The fields of application are (i) bone age assessment, (ii) bone fractures, (iii) interstitial lung diseases, and (iv) mammography. Bridging the particular gaps of semantics, feature extraction, feature structure, and evaluation have been addressed most frequently.
In specific application domains, CBIR technology is available for clinical practice. While system development has mainly focused on bridging content and feature gaps, performance and usability have become increasingly important. The evaluation must be based on a larger set of reference data, and workflow integration must be achieved before CBIR-CAD is really established in clinical practice.
Content-based image retrieval; medical image retrieval; diagnosis aid; prototypes.
Supported by National Science Foundation (NSF), International Society of Intelligent Biological Medicine (ISIBM), International Journal of Computational Biology and Drug Design and International Journal of Functional Informatics and Personalized Medicine, IEEE 7th Bioinformatics and Bioengineering attracted more than 600 papers and 500 researchers and medical doctors. It was the only synergistic inter/multidisciplinary IEEE conference with 24 Keynote Lectures, 7 Tutorials, 5 Cutting-Edge Research Workshops and 32 Scientific Sessions including 11 Special Research Interest Sessions that were designed dynamically at Harvard in response to the current research trends and advances. The committee was very grateful for the IEEE Plenary Keynote Lectures given by: Dr. A. Keith Dunker (Indiana), Dr. Jun Liu (Harvard), Dr. Brian Athey (Michigan), Dr. Mark Borodovsky (Georgia Tech and President of ISIBM), Dr. Hamid Arabnia (Georgia and Vice-President of ISIBM), Dr. Ruzena Bajcsy (Berkeley and Member of United States National Academy of Engineering and Member of United States Institute of Medicine of the National Academies), Dr. Mary Yang (United States National Institutes of Health and Oak Ridge, DOE), Dr. Chih-Ming Ho (UCLA and Member of United States National Academy of Engineering and Academician of Academia Sinica), Dr. Andy Baxevanis (United States National Institutes of Health), Dr. Arif Ghafoor (Purdue), Dr. John Quackenbush (Harvard), Dr. Eric Jakobsson (UIUC), Dr. Vladimir Uversky (Indiana), Dr. Laura Elnitski (United States National Institutes of Health) and other world-class scientific leaders. The Harvard meeting was a large academic event 100% full-sponsored by IEEE financially and academically. After a rigorous peer-review process, the committee selected 27 high-quality research papers from 600 submissions. The committee is grateful for contributions from keynote speakers Dr. Russ Altman (IEEE BIBM conference keynote lecturer on combining simulation and machine learning to recognize function in 4D), Dr. Mary Qu Yang (IEEE BIBM workshop keynote lecturer on new initiatives of detecting microscopic disease using machine learning and molecular biology, http://ieeexplore.ieee.org/servlet/opac?punumber=4425386) and Dr. Jack Y. Yang (IEEE BIBM workshop keynote lecturer on data mining and knowledge discovery in translational medicine) from the first IEEE Computer Society BioInformatics and BioMedicine (IEEE BIBM) international conference and workshops, November 2-4, 2007, Silicon Valley, California, USA.
Working under the auspices of the Institute of Electrical and Electronic Engineers Engineering in Medicine and Biology Society (IEEE EMBS), the IEEE P1157 Medical Data Interchange (MEDIX) Committee has been chartered with developing international standards for communication of medical information between heterogeneous healthcare information systems. The IEEE P1157 Standards are based upon, and will conform to, the International Standards Organization (ISO) Reference Model for Open Systems Interconnection (OSI).
The IEEE P1157 Committee has adopted a phased approach and is working towards balloting the initial standards, which apply to communications between a patient care system (PCS) and selected ancillaries in the medical center setting.
A parallel, longer range effort, focused on developing a reference model for electronic exchange of the medical record structure, content, and related medical knowledge, is in progress.
A report of the 5th IEEE International Conference on Systems Biology (IEEE ISB2011), 2-4 September 2011, Zhuhai, China.
We conducted in two parts a systematic review of randomized controlled trials (RCTs) on electronic symptom reporting between patients and providers to improve health care service quality. Part 1 reviewed the typology of patient groups, health service innovations, and research targets. Four innovation categories were identified: consultation support, monitoring with clinician support, self-management with clinician support, and therapy.
To assess the methodological quality of the RCTs, and summarize effects and benefits from the methodologically best studies.
We searched Medline, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, and IEEE Xplore for original studies presented in English-language articles between 1990 and November 2011. Risk of bias and feasibility were judged according to the Cochrane recommendation, and theoretical evidence and preclinical testing were evaluated according to the Framework for Design and Evaluation of Complex Interventions to Improve Health. Three authors assessed the risk of bias and two authors extracted the effect data independently. Disagreement regarding bias assessment, extraction, and interpretation of results were resolved by consensus discussions.
Of 642 records identified, we included 32 articles representing 29 studies. No articles fulfilled all quality requirements. All interventions were feasible to implement in a real-life setting, and theoretical evidence was provided for almost all studies. However, preclinical testing was reported in only a third of the articles. We judged three-quarters of the articles to have low risk for random sequence allocation and approximately half of the articles to have low risk for the following biases: allocation concealment, incomplete outcome data, and selective reporting. Slightly more than one fifth of the articles were judged as low risk for blinding of outcome assessment. Only 1 article had low risk of bias for blinding of participants and personnel. We excluded 12 articles showing high risk or unclear risk for both selective reporting and blinding of outcome assessment from the effect assessment. The authors’ hypothesis was confirmed for 13 (65%) of the 20 remaining articles. Articles on self-management support were of higher quality, allowing us to assess effects in a larger proportion of studies. All except one self-management interventions were equally effective to or better than the control option. The self-management articles document substantial benefits for patients, and partly also for health professionals and the health care system.
Electronic symptom reporting between patients and providers is an exciting area of development for health services. However, the research generally is of low quality. The field would benefit from increased focus on methods for conducting and reporting RCTs. It appears particularly important to improve blinding of outcome assessment and to precisely define primary outcomes to avoid selective reporting. Supporting self-management seems to be especially promising, but consultation support also shows encouraging results.
Electronic symptom reporting; physician-patient relationship; patient participation; shared decision making; review; consultation; monitoring; self-management; bias
Image registration is one of the most important and universally useful computational tasks in biomedical image analysis. A recent article by Xing & Qiu (IEEE Transactions on Pattern Analysis and Machine Intelligence, 33(10):2081–2092, 2011) is based on an inappropriately narrow conceptualization of the image registration problem as the task of making two images look alike, which disregards whether the established spatial correspondence is plausible. The authors propose a new algorithm, Nonparametric Local Smoothing (NLS) for image registration, but use image similarities alone as a measure of registration performance, although these measures do not relate reliably to the realism of the correspondence map.
Using data obtained from its authors, we show experimentally that the method proposed by Xing & Qiu is not an effective registration algorithm. While it optimizes image similarity, it does not compute accurate, interpretable transformations. Even judged by image similarity alone, the proposed method is consistently outperformed by a simple pixel permutation algorithm, which is known by design not to compute valid registrations.
This study has demonstrated that the NLS algorithm proposed recently for image registration, and published in one of the most respected journals in computer science, is not, in fact, an effective registration method at all. Our results also emphasize the general need to apply registration evaluation criteria that are sensitive to whether correspondences are accurate and mappings between images are physically interpretable. These goals cannot be achieved by simply reporting image similarities.
Image registration; Correspondence; Accuracy
Genetic Analysis Workshop 17 (GAW17) provided a platform for evaluating existing statistical genetic methods and for developing novel methods to analyze rare variants that modulate complex traits. In this article, we present an overview of the 1000 Genomes Project exome data and simulated phenotype data that were distributed to GAW17 participants for analyses, the different issues addressed by the participants, and the process of preparation of manuscripts resulting from the discussions during the workshop.
The electroencephalography (EEG) signal has a high complexity, and the process of extracting clinically relevant features is achieved by visual analysis of the recordings. The interobserver agreement in EEG interpretation is only moderate. This is partly due to the method of reporting the findings in free-text format. The purpose of our endeavor was to create a computer-based system for EEG assessment and reporting, where the physicians would construct the reports by choosing from predefined elements for each relevant EEG feature, as well as the clinical phenomena (for video-EEG recordings). A working group of EEG experts took part in consensus workshops in Dianalund, Denmark, in 2010 and 2011. The faculty was approved by the Commission on European Affairs of the International League Against Epilepsy (ILAE). The working group produced a consensus proposal that went through a pan-European review process, organized by the European Chapter of the International Federation of Clinical Neurophysiology. The Standardised Computer-based Organised Reporting of EEG (SCORE) software was constructed based on the terms and features of the consensus statement and it was tested in the clinical practice. The main elements of SCORE are the following: personal data of the patient, referral data, recording conditions, modulators, background activity, drowsiness and sleep, interictal findings, “episodes” (clinical or subclinical events), physiologic patterns, patterns of uncertain significance, artifacts, polygraphic channels, and diagnostic significance. The following specific aspects of the neonatal EEGs are scored: alertness, temporal organization, and spatial organization. For each EEG finding, relevant features are scored using predefined terms. Definitions are provided for all EEG terms and features. SCORE can potentially improve the quality of EEG assessment and reporting; it will help incorporate the results of computer-assisted analysis into the report, it will make possible the build-up of a multinational database, and it will help in training young neurophysiologists.
Assessment; Database; Definitions; EEG; Semiology; Terms
Our first predictor of protein disorder was published just over a decade ago in the Proceedings of the IEEE International Conference on Neural Networks (Romero P, Obradovic Z, Kissinger C, Villafranca JE, Dunker AK (1997) Identifying disordered regions in proteins from amino acid sequence. Proceedings of the IEEE International Conference on Neural Networks, 1: 90–95). By now more than twenty other laboratory groups have joined the efforts to improve the prediction of protein disorder. While the various prediction methodologies used for protein intrinsic disorder resemble those methodologies used for secondary structure prediction, the two types of structures are entirely different. For example, the two structural classes have very different dynamic properties, with the irregular secondary structure class being much less mobile than the disorder class. The prediction of secondary structure has been useful. On the other hand, the prediction of intrinsic disorder has been revolutionary, leading to major modifications of the more than 100 year-old views relating protein structure and function. Experimentalists have been providing evidence over many decades that some proteins lack fixed structure or are disordered (or unfolded) under physiological conditions. In addition, experimentalists are also showing that, for many proteins, their functions depend on the unstructured rather than structured state; such results are in marked contrast to the greater than hundred year old views such as the lock and key hypothesis. Despite extensive data on many important examples, including disease-associated proteins, the importance of disorder for protein function has been largely ignored. Indeed, to our knowledge, current biochemistry books don't present even one acknowledged example of a disorder-dependent function, even though some reports of disorder-dependent functions are more than 50 years old. The results from genome-wide predictions of intrinsic disorder and the results from other bioinformatics studies of intrinsic disorder are demanding attention for these proteins.
Disorder prediction has been important for showing that the relatively few experimentally characterized examples are members of a very large collection of related disordered proteins that are wide-spread over all three domains of life. Many significant biological functions are now known to depend directly on, or are importantly associated with, the unfolded or partially folded state. Here our goal is to review the key discoveries and to weave these discoveries together to support novel approaches for understanding sequence-function relationships.
Intrinsically disordered protein is common across the three domains of life, but especially common among the eukaryotic proteomes. Signaling sequences and sites of posttranslational modifications are frequently, or very likely most often, located within regions of intrinsic disorder. Disorder-to-order transitions are coupled with the adoption of different structures with different partners. Also, the flexibility of intrinsic disorder helps different disordered regions to bind to a common binding site on a common partner. Such capacity for binding diversity plays important roles in both protein-protein interaction networks and likely also in gene regulation networks. Such disorder-based signaling is further modulated in multicellular eukaryotes by alternative splicing, for which such splicing events map to regions of disorder much more often than to regions of structure. Associating alternative splicing with disorder rather than structure alleviates theoretical and experimentally observed problems associated with the folding of different length, isomeric amino acid sequences. The combination of disorder and alternative splicing is proposed to provide a mechanism for easily "trying out" different signaling pathways, thereby providing the mechanism for generating signaling diversity and enabling the evolution of cell differentiation and multicellularity. Finally, several recent small molecules of interest as potential drugs have been shown to act by blocking protein-protein interactions based on intrinsic disorder of one of the partners. Study of these examples has led to a new approach for drug discovery, and bioinformatics analysis of the human proteome suggests that various disease-associated proteins are very rich in such disorder-based drug discovery targets.
The first step to detect when a vineyard has any type of deficiency, pest or disease is to observe its stems, its grapes and/or its leaves. To place a sensor in each leaf of every vineyard is obviously not feasible in terms of cost and deployment. We should thus look for new methods to detect these symptoms precisely and economically. In this paper, we present a wireless sensor network where each sensor node takes images from the field and internally uses image processing techniques to detect any unusual status in the leaves. This symptom could be caused by a deficiency, pest, disease or other harmful agent. When it is detected, the sensor node sends a message to a sink node through the wireless sensor network in order to notify the problem to the farmer. The wireless sensor uses the IEEE 802.11 a/b/g/n standard, which allows connections from large distances in open air. This paper describes the wireless sensor network design, the wireless sensor deployment, how the node processes the images in order to monitor the vineyard, and the sensor network traffic obtained from a test bed performed in a flat vineyard in Spain. Although the system is not able to distinguish between deficiency, pest, disease or other harmful agents, a symptoms image database and a neuronal network could be added in order learn from the experience and provide an accurate problem diagnosis.
Wireless Sensor Network; image sensor; image processing; vineyard monitoring
The IEEE has gone to ballot on a "Standard for Medical Device Communications", IEEE P1073. The lower layer, hardware portions of the standard are expected to be approved by the IEEE Standards Board at their December 11-13, 1994 meeting. Other portions of the standard are in the initial stages of the IEEE ballot process. The intent of the standard is to allow hospitals and other users to interface medical electronic devices to host computer systems in a standard, interchangeable manner. The standard is optimized for acute care environments such as ICU's, operating rooms, and emergency rooms.  IEEE General Committee and Subcommittee work has been on-going since 1984. Significant amounts of work have been done to discover and meet the needs of the patient care setting. Surveys performed in 1989 identified the following four key user requirements for medical device communications: 1) Frequent reconfiguration of the network. 2) Allow "plug and play" operation by users. 3) Associate devices with a specific bed and patient. 4) Support a wide range of hospital computer system topologies. Additionally, the most critical difference in the acute care setting is patient safety, which has an overall effect on the standard. The standard that went to ballot meets these requirements. The standard is based on existing ISO standards. P1073 is compliant with the OSI seven layer model. P1073 specifies the entire communication stack, from object-oriented software to hospital unique connectors. The standard will be able to be put forward as a true international standard, much in the way that the IEEE 802.x family of standards (like Ethernet) were presented as draft ISO standards.(ABSTRACT TRUNCATED AT 250 WORDS)
Capacity building has been employed in international health and development sectors to describe the process of ‘experts’ from more resourced countries training people in less resourced countries. Hence the concept has an implicit power imbalance based on ‘expert’ knowledge. In 2011, a health research strengthening workshop was undertaken at Atoifi Adventist Hospital, Solomon Islands to further strengthen research skills of the Hospital and College of Nursing staff and East Kwaio community leaders through partnering in practical research projects. The workshop was based on participatory research frameworks underpinned by decolonising methodologies, which sought to challenge historical power imbalances and inequities. Our research question was, “Is research capacity strengthening a two-way process?”
In this qualitative study, five Solomon Islanders and five Australians each responded to four open-ended questions about their experience of the research capacity strengthening workshop and activities: five chose face to face interview, five chose to provide written responses. Written responses and interview transcripts were inductively analysed in NVivo 9.
Six major themes emerged. These were: Respectful relationships; Increased knowledge and experience with research process; Participation at all stages in the research process; Contribution to public health action; Support and sustain research opportunities; and Managing challenges of capacity strengthening. All researchers identified benefits for themselves, their institution and/or community, regardless of their role or country of origin, indicating that the capacity strengthening had been a two-way process.
The flexible and responsive process we used to strengthen research capacity was identified as mutually beneficial. Using community-based participatory frameworks underpinned by decolonising methodologies is assisting to redress historical power imbalances and inequities and is helping to sustain the initial steps taken to establish a local research agenda at Atoifi Hospital. It is our experience that embedding mutuality throughout the research capacity strengthening process has had great benefit and may also benefit researchers from more resourced and less resourced countries wanting to partner in research capacity strengthening activities.
Capacity building; Research capacity strengthening; Health research; Solomon Islands; Atoifi Adventist Hospital; Mutuality
The December 2011 5th International Workshop on HIV Persistence during Therapy addressed the issue of HIV persistence among 210 scientists from 10 countries involved in the study of HIV reservoirs and the search of an HIV cure. High quality abstracts were selected and discussed as oral or poster presentations. The aim of this review is to distribute the scientific highlights of this workshop outside the group as analyzed and represented by experts in retrovirology, immunology and clinical research.
HIV persistence; HIV reservoirs; HIV latency; HIV cure; HIV eradication; HIV reservoir group
The mini-CEX is a valid and reliable method to assess the clinical competencies of trainees. Its data could be useful for educators to redesign curriculum as a process of quality improvement. The aim of this study was to evaluate a mini-CEX assessment program in our internal medicine residency training. We investigated the impact of mini-CEX workshops as a faculty development program on the acquisition of cognitive knowledge and the difference of practice behaviors among faculty members used the mini-CEX to assess residents’ performance at work.
We designed an observational, two-phase study. In the faculty development program, we started a mini-CEX workshop for trainers in 2010, and the short-term outcome of the program was evaluated by comparing the pretest and posttest results to demonstrate the improvement in cognitive knowledge on mini-CEX. From September 2010 to August 2011, we implemented a monthly mini-CEX assessment program in our internal medicine residency training. The data of these mini-CEX assessment forms were collected and analyzed.
In the group of 49 mini-CEX workshop attendees, there was a statistically significant improvement in cognitive knowledge by comparing the pretest and posttest results (67.35 ± 15.25 versus 81.22 ± 10.34, p < 0.001). Among the 863 clinical encounters of mini-CEX, which involved 97 residents and 139 evaluators, 229 (26.5%), 326 (37.8%), and 308 (35.7%) evaluations were completed by the first-year, second-year, and third- year residents separately. We found a statistically significant interaction between level of training and score in dimensions of mini-CEX. The scores in all dimensions measured were better for senior residents. Participation in mini-CEX workshops as a faculty development program strengthened the adherence of trainers to the principles of mini-CEX as a formative assessment in regard to provision of feedback. However, a deficiency in engaging residents’ reflection was found.
Faculty development is a prerequisite to train evaluators in order to implement a successful mini-CEX assessment program. We demonstrated the effectiveness of our mini-CEX workshops in terms of knowledge acquisition and enhancement of giving feedback when the faculty members used the tool. Further programs on providing effective feedback should be conducted to increase the impact of the mini-CEX as a formative assessment.
Mini-CEX; Mini clinical evaluation exercise; Faculty development
Research ethics is predominantly taught and practiced in Anglophone countries, particularly those in North America and Western Europe. Initiatives to build research ethics capacity in developing countries must attempt to avoid imposing foreign frameworks and engage with ethical issues in research that are locally relevant. This article describes the process and outcomes of a capacity-building workshop that took place in Kinshasa, Democratic Republic of Congo in the summer of 2011. Although the workshop focused on a specific ethical theme – the responsibilities of researchers to provide health-related care to their research participants – we argue that the structure of the workshop offers a useful method for engaging with research ethics in general, and the theme of ancillary care encourages a broad perspective on research ethics that is highly pertinent in low-income countries. The workshop follows an interactive, locally driven model that could be fruitfully replicated in similar settings.
Research ethics; Developing countries; Francophone Africa; Ancillary care; Medical education
The 22nd Annual Antibody Engineering and 9th Annual Antibody Therapeutics international conferences, and the 2011 Annual Meeting of The Antibody Society, organized by IBC Life Sciences with contributions from The Antibody Society and two Scientific Advisory Boards, were held December 5–8, 2011 in San Diego, CA. The meeting drew ∼800 participants who attended sessions on a wide variety of topics relevant to antibody research and development. As a preview to the main events, a pre-conference workshop held on December 4, 2011 focused on antibodies as probes of structure. The Antibody Engineering Conference comprised eight sessions: (1) structure and dynamics of antibodies and their membrane receptor targets; (2) model-guided generation of binding sites; (3) novel selection strategies; (4) antibodies in a complex environment: targeting intracellular and misfolded proteins; (5) rational vaccine design; (6) viral retargeting with engineered binding molecules; (7) the biology behind potential blockbuster antibodies and (8) antibodies as signaling modifiers: where did we go right, and can we learn from success? The Antibody Therapeutics Conference comprised five sessions: (1) Twenty-five years of therapeutic antibodies: lessons learned and future challenges; (2) preclinical and early stage development of antibody therapeutics; (3) next generation anti-angiogenics; (4) updates of clinical stage antibody therapeutics and (5) antibody drug conjugates and bispecific antibodies.
antibody engineering; antibody therapeutics; antibody-drug conjugates; bispecific antibodies; computational design; antibody-antigen structure; vaccine design
Note from Anna B. Reisman, Co-Director, Yale Internal Medicine Residency Writers’ Workshop, Assistant Professor, Department of Internal Medicine, Yale University School of Medicine and VA Connecticut Health Care System: This issue inaugurates a new feature: selected writings from the Yale Internal Medicine Residency Program’s Writers’ Workshop. The annual workshop began in 2003. Abraham Verghese and Richard Selzer, among the best known physician-writers in the United States, have served as workshop leaders, teaching the craft of writing to more than 35 residents. In designing the workshop with my co-director, Dr. Asghar Rastegar, our aim was to make participants better physicians by providing a creative outlet for reflection. The tempo of a resident’s day is typically furious — one patient dies, perhaps, another sickens, a third refuses a necessary procedure, a fourth’s wife cries inconsolably at the bedside — with no time in between to ponder what happened, much less what it meant to the patient or to the resident and how it might shape the way the resident practices medicine in the future. Without time to muse about the experience, many residents take the easy road: They emotionally detach. Writing, we believe, can be an antidote to this tendency. The exercise of writing not only makes us empathic; it also sharpens our diagnostic skills. One of the keys to compelling writing is attention to detail: the nervous twitch of an old man’s eye muscles or the decayed front teeth of a young woman, a former crack addict. Such details not only make our writing come alive but also sensitize us to our patients’ plights and sharpen our diagnostic skills. The stories and essays written by the Writers’ Workshop participants present a range of experiences, real and imagined, and take us deep into the minds of young doctors trying to make sense of what they do.
This special issue on nanoinformatics for biomedicine is a collection of recent papers from the 2012 IEEE Workshop on Nanoinformatics for Biomedicine (NanoInfo 2012) and other work in the area. These papers illustrate different aspects of nanoinformatics to support biomedical research and to advance knowledge on nanomaterial–biological interactions. The topics covered include data curation, data standards, data mining and predictive modeling, machine learning, and translational research. The objectives of this special issue are multifold: (1) to bring together and showcase some of the latest research results in the field; (2) to introduce some useful repositories, systems, and analysis tools; and (3) to stimulate more research activities in the field.
nanobiotechnology; nanoinformatics; data curation; data mining; machine learning; translational research
We report here that a human immunodeficiency virus type 1 (HIV-1)-specific neutralizing monoclonal antibody (MAb 1575) mapped to the conserved putative intracellular region from amino acid residues 735 to 752 (735-752 region) of gp41 also recognizes a region in an extracellular portion of p17. Both epitopes have a core recognition sequence (IEEE) in a nonhomologous context. The IEEE motif found in HIV-1 p17 is located in a region known as HGP-30 (residues 86 to 115) which has been previously associated with virus neutralization, cytotoxic T lymphocyte activity, and mother-to-child transmission. An analysis of available gp41 and p17 sequences demonstrates that in these regions both IEEE sequences are highly conserved in different HIV-1 clades. The presence of the IEEE epitope in p17 allows us to explain some unexpected neutralizing characteristics of MAb 1575. In addition, the gp41 735-752 region has been previously reported both in intra- and extracellular locations. Our results suggest that the extracellular location was the result of cross-reactivity with p17.
This is the second issue featuring a selected piece from the Yale Internal Medicine Residency Program's Writers' Workshop. The annual workshop began in 2003. Abraham Verghese and Richard Selzer, among the best known physician-writers in the United States, have served as workshop leaders, teaching the craft of writing to more than 35 residents. In designing the workshop, Anna B. Reisman, assistant professor in the Department of Internal Medicine at the Yale University School of Medicine and VA Connecticut Health Care System, and Dr. Asghar Rastegar had the goal of making participants better physicians by providing a creative outlet for reflection.The stories and essays written by the Writers' Workshop participants present a range of experiences, real and imagined, and take readers deep into the minds of young doctors trying to make sense of what they do.
Efforts to annotate the genomes of a wide variety of model organisms are currently carried out by sequencing centers, model organism databases and academic/institutional laboratories around the world. Different annotation methods and tools have been developed over time to meet the needs of biologists faced with the task of annotating biological data. While standardized methods are essential for consistent curation within each annotation group, methods and tools can differ between groups, especially when the groups are curating different organisms. Biocurators from several institutes met at the Third International Biocuration Conference in Berlin, Germany, April 2009 and hosted the ‘Best Practices in Genome Annotation: Inference from Evidence’ workshop to share their strategies, pipelines, standards and tools. This article documents the material presented in the workshop.
Climate and human influences on marine ecosystems are largely manifested by changes in predator–prey interactions. It follows that ecosystem-based management of the world's oceans requires a better understanding of food web relationships. An international workshop on predator–prey interactions in marine ecosystems was held at the Oregon State University, Corvallis, OR, USA on 16–18 March 2010. The meeting brought together scientists from diverse fields of expertise including theoretical ecology, animal behaviour, fish and seabird ecology, statistics, fisheries science and ecosystem modelling. The goals of the workshop were to critically examine the methods of scaling-up predator–prey interactions from local observations to systems, the role of shifting ecological processes with scale changes, and the complexity and organizational structure in trophic interactions.
predator–prey; food webs; scaling; marine ecosystems
In September of 2011, the National Institute of Neurological Disorders and Stroke (NINDS), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the International Rett Syndrome Foundation (IRSF) and the Rett Syndrome Research Trust (RSRT) convened a workshop involving a broad cross-section of basic scientists, clinicians and representatives from the National Institutes of Health (NIH), the US Food and Drug Administration (FDA), the pharmaceutical industry and private foundations to assess the state of the art in animal studies of Rett syndrome (RTT). The aim of the workshop was to identify crucial knowledge gaps and to suggest scientific priorities and best practices for the use of animal models in preclinical evaluation of potential new RTT therapeutics. This review summarizes outcomes from the workshop and extensive follow-up discussions among participants, and includes: (1) a comprehensive summary of the physiological and behavioral phenotypes of RTT mouse models to date, and areas in which further phenotypic analyses are required to enhance the utility of these models for translational studies; (2) discussion of the impact of genetic differences among mouse models, and methodological differences among laboratories, on the expression and analysis, respectively, of phenotypic traits; and (3) definitions of the standards that the community of RTT researchers can implement for rigorous preclinical study design and transparent reporting to ensure that decisions to initiate costly clinical trials are grounded in reliable preclinical data.
Hormones influence countless biological processes across the lifespan, and during developmental sensitive periods hormones have the potential to cause permanent tissue-specific alterations in anatomy and physiology. There are numerous critical periods in development wherein different targets are affected. This review outlines the proceedings of the Hormonal Programming in Development session at the US-South American Workshop in Neuroendocrinology in August 2011. Here we discuss how gonadal hormones impact various biological processes within the brain and gonads during early development and describe the changes that take place in the aging female ovary. At the cellular level, hormonal targets in the brain include neurons, glia, or vasculature. On a genomic/epigenomic level, transcription factor signaling and epigenetic changes alter the expression of hormone receptor genes across development and following ischemic brain insult. In addition, organizational hormone exposure alters epigenetic processes in specific brain nuclei and may be a mediator of sexual differentiation of the neonatal brain. During development of the ovary, exposure to excess gonadal hormones leads to polycystic ovarian syndrome (PCOS). Exposure to excess androgens during fetal development also has a profound effect on the development of the male reproductive system. In addition, increased sympathetic nerve activity and stress during early life have been linked to PCOS symptomology in adulthood. Finally, we describe how age-related decreases in fertility are linked to high levels of nerve growth factor (NGF), which enhances sympathetic nerve activity and alters ovarian function.
Gonadal hormones; Development; Aging; Brain; Ovary; Stress
Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a neurogenetic disorder associated with neurocognitive impairments. This article focuses on the cortical gyrification changes that are associated with the genetic disorder in 6–15-year-old children with 22q11.2DS, when compared with a group of age-matched typically developing (TD) children. Local gyrification index (lGI; Schaer et al. : IEEE Trans Med Imaging 27:161–170) was used to characterize the cortical gyrification at each vertex of the pial surface. Vertex-wise statistical analysis of lGI differences between the two groups revealed cortical areas of significant reduction in cortical gyrification in children with 22q11.2DS, which were mainly distributed along the medial aspect of each hemisphere. To gain further insight into the developmental trajectory of the cortical gyrification, we examined age as a factor in lGI changes over the 6–15 years of development, within and across the two groups of children. Our primary results pertaining to the developmental trajectory of cortical gyrification revealed cortical regions where the change in lGI over the 6–15 years of age was significantly modulated by diagnosis, implying an atypical development of cortical gyrification in children with 22q11.2DS, when compared with the TD children. Significantly, these cortical areas included parietal structures that are associated, in typical individuals, with visuospatial, attentional, and numerical cognition tasks in which children with 22q11.2DS show impairments.
22q11.2DS; development; cortex; gyrification; impairment