The histological study of arteries with implanted metallic scaffolding devices, known as stents, remains a technical challenge. Given that the arterial response to stent implantation can sometimes lead to adverse outcomes, including the re-accumulation of tissue mass within the stent (or in-stent restenosis), overcoming these technical challenges is a priority for the advancement of research and development in this important clinical field. Essentially, the task is to section the stent-tissue interface with the least amount of disruption of tissue and cellular morphology. Although many methacrylate resin methodologies are successfully applied toward the study of endovascular stents by a variety of research laboratories, the exact formulations, as well as subsequent processing and sectioning methodology, remain largely coveted. In this paper, we describe in detail a methyl methacrylate resin-embedding methodology that can successfully be applied to tungsten carbide blade, as well as saw and grinding sectioning methods and transmission electron microscopy. In addition, we present a comparison of the two sectioning methodologies in terms of their effectiveness with regard to morphological, histochemical, and immunohistochemical analyses. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials.

The Rbfox genes encode an ancient family of sequence-specific RNA binding proteins (RBPs) that are critical developmental regulators in multiple tissues including skeletal muscle, cardiac muscle, and brain. The hallmark of Rbfox proteins is a single high-affinity RRM domain, highly conserved from insects to humans, that binds preferentially to UGCAUG motifs at diverse regulatory sites in pre-mRNA introns, mRNA 3'UTRs, and pre-miRNAs hairpin structures. Versatile regulatory circuits operate on Rbfox pre-mRNA and mRNA to ensure proper expression of Rbfox1 protein isoforms, which then act on the broader transcriptome to regulate alternative splicing networks, mRNA stability and translation, and microRNA processing. Complex Rbfox expression is encoded in large genes encompassing multiple promoters and alternative splicing options that govern spatiotemporal expression of structurally distinct and tissue-specific protein isoforms with different classes of RNA targets. Nuclear Rbfox1 is a candidate master regulator that binds intronic UGCAUG elements to impact splicing efficiency of target alternative exons, many in transcripts for other splicing regulators. Tissue-specificity of Rbfox-mediated alternative splicing is executed by combinatorial regulation through the integrated activity of Rbfox proteins and synergistic or antagonistic splicing factors. Studies in animal models show that Rbfox1-related genes are critical for diverse developmental processes including germ cell differentiation and memory in Drosophila, neuronal migration and function in mouse brain, myoblast fusion and skeletal muscle function, and normal heart function. Finally, genetic and biochemical evidence suggest that aberrations in Rbfox-regulated circuitry are risk factors for multiple human disorders, especially neurodevelopmental disorders including epilepsy and autism, and cardiac hypertrophy. WIREs RNA 2017, 8:e1398. doi: 10.1002/wrna.1398 For further resources related to this article, please visit the WIREs website.

BACKGROUND

Regular breakfast consumption may protect against type 2 diabetes risk in adults but little is known about its influence on type 2 diabetes risk markers in children. We investigated the associations between breakfast consumption (frequency and content) and risk markers for type 2 diabetes (particularly insulin resistance and glycaemia) and cardiovascular disease in children.

RESULTS

We conducted a cross-sectional study of 4,116 UK primary school children aged 9-10 years. Participants provided information on breakfast frequency, had measurements of body composition, and gave fasting blood samples for measurements of blood lipids, insulin, glucose, and glycated haemoglobin (HbA1c). A subgroup of 2,004 children also completed a 24-hour dietary recall. Among 4,116 children studied, 3,056 (74%) ate breakfast daily, 450 (11%) most days, 372 (9%) some days, and 238 (6%) not usually. Graded associations between breakfast frequency and risk markers were observed; children who reported not usually having breakfast had higher fasting insulin (percent difference 26.4%, 95% CI 16.6%-37.0%), insulin resistance (percent difference 26.7%, 95% CI 17.0%-37.2%), HbA1c (percent difference 1.2%, 95% CI 0.4%-2.0%), glucose (percent difference 1.0%, 95% CI 0.0%-2.0%), and urate (percent difference 6%, 95% CI 3%-10%) than those who reported having breakfast daily; these differences were little affected by adjustment for adiposity, socioeconomic status, and physical activity levels. When the higher levels of triglyceride, systolic blood pressure, and C-reactive protein for those who usually did not eat breakfast relative to those who ate breakfast daily were adjusted for adiposity, the differences were no longer significant. Children eating a high fibre cereal breakfast had lower insulin resistance than those eating other breakfast types (p for heterogeneity <0.01). Differences in nutrient intakes between breakfast frequency groups did not account for the differences in type 2 diabetes markers.

CONCLUSIONS

Children who ate breakfast daily, particularly a high fibre cereal breakfast, had a more favourable type 2 diabetes risk profile. Trials are needed to quantify the protective effect of breakfast on emerging type 2 diabetes risk. Please see later in the article for the Editors' Summary.

Removal of the 5' end cap is a critical determinant controlling mRNA stability and efficient gene expression. Removal of the cap is exquisitely controlled by multiple direct and indirect regulators that influence association with the cap and the catalytic step. A subset of these factors directly stimulate activity of the decapping enzyme, while others influence remodeling of factors bound to mRNA and indirectly stimulate decapping. Furthermore, the components of the general decapping machinery can also be recruited by mRNA-specific regulatory proteins to activate decapping. The Nudix hydrolase, Dcp2, identified as a first decapping enzyme, cleaves capped mRNA and initiates 5'-3' degradation. Extensive studies on Dcp2 led to broad understanding of its activity and the regulation of transcript specific decapping and decay. Interestingly, seven additional Nudix proteins possess intrinsic decapping activity in vitro and at least two, Nudt16 and Nudt3, are decapping enzymes that regulate mRNA stability in cells. Furthermore, a new class of decapping proteins within the DXO family preferentially function on incompletely capped mRNAs. Importantly, it is now evident that each of the characterized decapping enzymes predominantly modulates only a subset of mRNAs, suggesting the existence of multiple decapping enzymes functioning in distinct cellular pathways. WIREs RNA 2017, 8:e1379. doi: 10.1002/wrna.1379 For further resources related to this article, please visit the WIREs website.

Probabilistic models based on Bayes' rule are an increasingly popular approach to understanding human cognition. Bayesian models allow immense representational latitude and complexity. Because they use normative Bayesian mathematics to process those representations, they define optimal performance on a given task. This article focuses on key mechanisms of Bayesian information processing, and provides numerous examples illustrating Bayesian approaches to the study of human cognition. We start by providing an overview of Bayesian modeling and Bayesian networks. We then describe three types of information processing operations-inference, parameter learning, and structure learning-in both Bayesian networks and human cognition. This is followed by a discussion of the important roles of prior knowledge and of active learning. We conclude by outlining some challenges for Bayesian models of human cognition that will need to be addressed by future research. WIREs Cogn Sci 2011 2 8-21 DOI: 10.1002/wcs.80 For further resources related to this article, please visit the WIREs website.

In June 2008, the editors of Chaos decided to institute a new section to appear from time to time that addresses timely and controversial topics related to nonlinear science. The first of these deals with the dynamical characterization of human heart rate variability. We asked authors to respond to the following questions: Is the normal heart rate chaotic? If the normal heart rate is not chaotic, is there some more appropriate term to characterize the fluctuations (e.g., scaling, fractal, multifractal)? How does the analysis of heart rate variability elucidate the underlying mechanisms controlling the heart rate? Do any analyses of heart rate variability provide clinical information that can be useful in medical assessment (e.g., in helping to assess the risk of sudden cardiac death)? If so, please indicate what additional clinical studies would be useful for measures of heart rate variability to be more broadly accepted by the medical community. In addition, as a challenge for analysis methods, PhysioNet [A. L. Goldberger et al., "PhysioBank, PhysioToolkit, and PhysioNet: Components of a new research resource for complex physiologic signals," Circulation 101, e215-e220 (2000)] provided data sets from 15 patients of whom five were normal, five had heart failure, and five had atrial fibrillation (http://www.physionet.org/challenge/chaos/). This introductory essay summarizes the main issues and introduces the essays that respond to these questions.

A teratoma is a benign tumor containing a mixture of differentiated tissues and organotypic derivatives of the three germ layers, while a teratocarcinoma also contains embryonal carcinoma cells (EC cells). Experimental teratomas and teratocarcinomas have been derived from early mammalian embryos transplanted into the adult animal (ectopic sites). In the rat, the pluripotency of the transplanted epiblast was demonstrated and a quantifiable restriction of developmental potential persisted after subsequent transplantation of chemically defined cultivated postimplantation embryos. The rat is nonpermissive for teratocarcinoma development and rat pluripotent cell lines have been established only recently. Transplantation of mouse embryos, epiblast, or embryonic stem cells (mESCs) gave rise to teratocarcinomas. The pluripotency of reprogrammed human cells has been tested by a 'gold standard' trilaminar teratoma assay in immunocompromised mice in vivo. Human pluripotent stem cells proposed for use in regenerative medicine such as human embryonic stem cell (hESC), human nuclear-transfer/therapeutic cloning embryonic stem cell (NT-ESC), or human induced pluripotent stem cell (hiPSC) lines, once differentiated in vitro to the desired cell type, should be again tested in a long-term animal teratoma assay to exclude their malignancy. Such an approach led to a recently implemented human therapy with retinal pigmented epithelium. For greater biosafety, the teratoma assay should be standardized and complemented by assessments of mutations/epimutations, RNA/protein expression, and possible immunogenicity of autologous pluripotent cells. Furthermore, the standardized teratoma assay should be directed more to the assessment of EC/malignant cell features than of differentiated tissues, especially after a unique case of human therapy with neural stem cells was found to lead to malignancy. For further resources related to this article, please visit the WIREs website.

The Motorik-Modul (MoMo) Longitudinal Study aims to contribute to long-term improvement in the health of German children and adolescents by focusing on: (i) the development of physical fitness and physical activity (including period effects); (ii) the individual and physical/social environmental determinants of the development of physical fitness and physical activity; and (iii) the impact of physical fitness and physical activity on the development of physical and mental health. The MoMo Longitudinal Study began with a nationwide representative sample of 4529 children and adolescents who ranged in age from 4-17 years at the study baseline (2003-2006). The first survey wave of the MoMo Longitudinal Study was conducted between 2009 and 2012, with two subsequent survey waves to be conducted between 2014 and 2016 and 2018 and 2020, respectively. The MoMo Longitudinal Study includes a physical fitness test profile, a physical activity questionnaire, and subjective and objective measures of health from the German Health Interview and Examination Survey (KiGGS). Data access is provided on request (alexander.woll@kit.edu). For further information, including a complete list of publications please visit www.motorik-modul.de.

Phototherapy with narrow-band UVB (NB-UVB), with a peak exclusively at 311 nm wavelength, has been found to be more effective in treating a variety of skin diseases than conventional broad-band UVB (BB-UVB). To assess the difference in carcinogenic activity between NB-UVB and BB-UVB, we investigated skin tumor formation by irradiating albino hairless, Ogg1 knockout mice and C57BL/6J wild counterparts with these two UV sources. We found that the ratio of malignant skin tumors induced by NB-UVB was significantly higher than that induced by BB-UVB. There was no significant difference in carcinogenicity of skin tumor induced by NB-UVB between Ogg1 knockout and wild-type mice. To investigate the possible cause of different carcinogenic activity by the different UV sources, we examined three types of DNA damage: cyclobutane pyrimidine dimer (CPD), (6-4) photoproduct, and 8-oxoguanine (8-oxoG) induced by each UV source. We found that CPD formation following a minimum erythema dose (MED) by NB-UVB was significantly higher than that following 1 MED by BB-UVB, whereas the formation of (6-4) photoproducts and 8-oxoG following BB-UVB was significantly higher than those following NB-UVB exposure. These results suggest that CPD formation is closely related to the higher carcinogenic characteristics of NB-UVB. JID JOURNAL CLUB ARTICLE: For questions, answers and open discussion about this article please go to http://network.nature.com/.

BACKGROUND

Death is the most extreme consequence of intimate partner violence. Female homicide studies with data on the perpetrator-victim relationship can provide insights. We compare the results of two South African national studies of female homicide with similar sampling done 10 y apart.

RESULTS

We conducted a retrospective national survey using a weighted cluster design of a proportionate random sample of 38 mortuaries to identify homicides committed in 2009. We abstracted victim data from mortuary and autopsy reports, and perpetrator data from police interviews. We compared homicides of women 14 y and older in 2009 with previously published data collected with the same methodology for homicides committed in 1999. The study found that the rate of female homicide per 100,000 female population in 2009 was 12.9 (95% confidence interval [CI]: 9.3, 16.5), compared to 24.7 (95% CI: 17.7, 31.6) in 1999. The incidence rate ratio of 0.54 (95% CI: 0.20, 0.84) reflects a significantly lower rate in 2009. The rate of intimate partner femicide was 5.6/100,000 in 2009 versus 8.8/100,000 in 1999, with an incidence rate ratio of 0.63 (95% CI: 0.24, 1.02), indicating no difference between rates. Logistic regression analysis of homicide characteristics showed that the odds ratio of suspected rape among non-intimate femicides in 2009 compared to 1999 was 2.61 (95% CI: 1.23, 4.08) and among intimate partner femicides it was 0.84 (95% CI: 0.50, 1.42). The OR of homicide by gunshot was 0.54 (95% CI: 0.30, 0.99) in 2009 versus 1999. There was a significant drop in convictions of perpetrators of non-intimate femicide in 2009 versus 1999 (OR = 0.32 [95% CI: 0.19, 0.53]). Limitations of the study include the relatively small sample size and having only two time points.

CONCLUSIONS

Female homicide in South Africa was lower in 2009 than 1999, but intimate partner femicide and suspected rape homicide rates were not statistically different. The cause of the difference is unknown. The findings suggest that South Africa needs greater efforts nationally to implement evidence-based violence prevention. Please see later in the article for the Editors' Summary.

BACKGROUND

The measurement of health status of the elderly remains one important topic. Self-rated health status (SRH) is considered to be a simple indicator to measure the health status of the old population. But some researchers still take a skeptical view about its reliability. This study aims to investigate the association between SRH indicator and health status of the elderly and discuss its subsequent public health implications.

METHODS

In a total 1096 people who were 60 years of age or older from 1784 households from a suburban area of Beijing were interviewed using multistage stratified cluster sampling. SRH was measured by a single question "please choose one point in this 0-100 scale, which can best represent your health today." The disease status and physical functional status were also obtained. A multiple linear regression was conducted to test the associate between SRH and individual's disease/functional status.

RESULTS

The average of SRH scores of the elderly was 72.49 ± 15.64 (on a 1-100 scale). The SRH scores declined not only with the severity of self-reported mental/disease status, but also with the decrease of physical functional status. Multiple linear regression showed that after adjustment for other variables, 2-week sickness, chronic diseases, hospitalization, and ability of self-care (washing and dressing) were able to explain 35% of the variation in SRH among the elderly. Among them, disease status and self-care ability were the most powerful predictor of SRH. After adjusting other variables, physical functional status could explain only 5% of the variation in SRH.

CONCLUSIONS

Self-rated health reflects the disease/functional health status of the elderly. It is an easy-to-implement variable and it can reduce both recall bias and investigator bias, thus being widely used in health surveys. It is a cost-effective means of measuring the health status. However, the comparability of SRH in different populations should be studied in future.

Screening for pulmonary metastatic disease is an important step for staging a patient with a known or recently discovered malignancy. Here we present our recommendations for screening for metastatic disease based on recommendations from the literature and experiences of pulmonary radiologists. In short, chest computed tomographic (CT) screening is the most appropriate tool for evaluation of pulmonary metastasis in the majority of cases. Chest computed tomographic screening is also recommended for follow-up and to determine response to therapy. Other modalities such as chest radiography, magnetic resonance imaging, and scintigraphy will also be discussed. Please note that this study is a summary of the complete version of this topic, which is available on the ACR website at www.acr.org. Practitioners are encouraged to refer to the complete version.

Quality control processes are widespread and play essential roles in detecting defective molecules and removing them in order to maintain organismal fitness. Aberrant messenger RNA (mRNA) molecules, unless properly managed, pose a significant hurdle to cellular proteostasis. Often mRNAs harbor premature stop codons, possess structures that present a block to the translational machinery, or lack stop codons entirely. In eukaryotes, the three cytoplasmic mRNA-surveillance processes, nonsense-mediated decay (NMD), no-go decay (NGD), and nonstop decay (NSD), evolved to cope with these aberrant mRNAs, respectively. Nonstop mRNAs and mRNAs that inhibit translation elongation are especially problematic as they sequester valuable ribosomes from the translating ribosome pool. As a result, in addition to RNA degradation, NSD and NGD are intimately coupled to ribosome rescue in all domains of life. Furthermore, protein products produced from all three classes of defective mRNAs are more likely to malfunction. It is not surprising then that these truncated nascent protein products are subject to degradation. Over the past few years, many studies have begun to document a central role for the ribosome in initiating the RNA and protein quality control processes. The ribosome appears to be responsible for recognizing the target mRNAs as well as for recruiting the factors required to carry out the processes of ribosome rescue and nascent protein decay. WIREs RNA 2017, 8:e1366. doi: 10.1002/wrna.1366 For further resources related to this article, please visit the WIREs website.

Spatial navigation in the absence of vision has been investigated from a variety of perspectives and disciplines. These different approaches have progressed our understanding of spatial knowledge acquisition by blind individuals, including their abilities, strategies, and corresponding mental representations. In this review, we propose a framework for investigating differences in spatial knowledge acquisition by blind and sighted people consisting of three longitudinal models (i.e., convergent, cumulative, and persistent). Recent advances in neuroscience and technological devices have provided novel insights into the different neural mechanisms underlying spatial navigation by blind and sighted people and the potential for functional reorganization. Despite these advances, there is still a lack of consensus regarding the extent to which locomotion and wayfinding depend on amodal spatial representations. This challenge largely stems from methodological limitations such as heterogeneity in the blind population and terminological ambiguity related to the concept of cognitive maps. Coupled with an over-reliance on potential technological solutions, the field has diffused into theoretical and applied branches that do not always communicate. Here, we review research on navigation by congenitally blind individuals with an emphasis on behavioral and neuroscientific evidence, as well as the potential of technological assistance. Throughout the article, we emphasize the need to disentangle strategy choice and performance when discussing the navigation abilities of the blind population. For further resources related to this article, please visit the WIREs website.

Children use syntax to guide verb learning in a process known as syntactic bootstrapping. Recent work explores how syntactic bootstrapping works-how it begins, and how it interacts with progress in syntax acquisition. We review evidence for three claims about the mechanisms and representations underlying syntactic bootstrapping: (1) Learners are biased to represent linguistic knowledge in a usefully abstract mental vocabulary, permitting rapid generalization of newly acquired syntactic knowledge to new verbs. (2) Toddlers collect information about each verb's combinatorial behavior in sentences based on listening experience, before they know anything about the verb's semantic content. (3) Syntactic bootstrapping begins with an unlearned bias to map nouns in sentences one-to-one onto the participant roles in events. These lines of evidence point toward a picture of early verb learning in which shallow structural analyses of sentences are intrinsically meaningful to learners, and in which information about verbs' combinatorial behavior pervades the lexicon from very early in development. Copyright © 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website.

The vertebrate vasculature displays high organotypic specialization, with the structure and function of blood vessels catering to the specific needs of each tissue. A unique feature of the central nervous system (CNS) vasculature is the blood-brain barrier (BBB). The BBB regulates substance influx and efflux to maintain a homeostatic environment for proper brain function. Here, we review the development and cell biology of the BBB, focusing on the cellular and molecular regulation of barrier formation and the maintenance of the BBB through adulthood. We summarize unique features of CNS endothelial cells and highlight recent progress in and general principles of barrier regulation. Finally, we illustrate why a mechanistic understanding of the development and maintenance of the BBB could provide novel therapeutic opportunities for CNS drug delivery. Expected final online publication date for the Annual Review of Cell and Developmental Biology Volume 35 is October 7, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Gene expression is regulated through the activity of transcription factors (TFs) and chromatin-modifying proteins acting on specific DNA sequences, referred to as cis-regulatory elements. These include promoters, located at the transcription initiation sites of genes, and a variety of distal cis-regulatory modules (CRMs), the most common of which are transcriptional enhancers. Because regulated gene expression is fundamental to cell differentiation and acquisition of new cell fates, identifying, characterizing, and understanding the mechanisms of action of CRMs is critical for understanding development. CRM discovery has historically been challenging, as CRMs can be located far from the genes they regulate, have few readily identifiable sequence characteristics, and for many years were not amenable to high-throughput discovery methods. However, the recent availability of complete genome sequences and the development of next-generation sequencing methods have led to an explosion of both computational and empirical methods for CRM discovery in model and nonmodel organisms alike. Experimentally, CRMs can be identified through chromatin immunoprecipitation directed against TFs or histone post-translational modifications, identification of nucleosome-depleted 'open' chromatin regions, or sequencing-based high-throughput functional screening. Computational methods include comparative genomics, clustering of known or predicted TF-binding sites, and supervised machine-learning approaches trained on known CRMs. All of these methods have proven effective for CRM discovery, but each has its own considerations and limitations, and each is subject to a greater or lesser number of false-positive identifications. Experimental confirmation of predictions is essential, although shortcomings in current methods suggest that additional means of validation need to be developed. For further resources related to this article, please visit the WIREs website.

BACKGROUND

The authors have declared no conflicts of interest for this article.

BACKGROUND

Given the lack of complete vital registration data in most developing countries, for many countries it is not possible to accurately estimate under-five mortality rates from vital registration systems. Heavy reliance is often placed on direct and indirect methods for analyzing data collected from birth histories to estimate under-five mortality rates. Yet few systematic comparisons of these methods have been undertaken. This paper investigates whether analysts should use both direct and indirect estimates from full birth histories, and under what circumstances indirect estimates derived from summary birth histories should be used.

RESULTS

Usings Demographic and Health Surveys data from West Africa, East Africa, Latin America, and South/Southeast Asia, I quantify the differences between direct and indirect estimates of under-five mortality rates, analyze data quality issues, note the relative effects of these issues, and test whether these issues explain the observed differences. I find that indirect estimates are generally consistent with direct estimates, after adjustment for fertility change and birth transference, but don't add substantial additional insight beyond direct estimates. However, choice of direct or indirect method was found to be important in terms of both the adjustment for data errors and the assumptions made about fertility.

CONCLUSIONS

Although adjusted indirect estimates are generally consistent with adjusted direct estimates, some notable inconsistencies were observed for countries that had experienced either a political or economic crisis or stalled health transition in their recent past. This result suggests that when a population has experienced a smooth mortality decline or only short periods of excess mortality, both adjusted methods perform equally well. However, the observed inconsistencies identified suggest that the indirect method is particularly prone to bias resulting from violations of its strong assumptions about recent mortality and fertility. Hence, indirect estimates of under-five mortality rates from summary birth histories should be used only for populations that have experienced either smooth mortality declines or only short periods of excess mortality in their recent past. Please see later in the article for the Editors' Summary.

BACKGROUND

The under-five mortality rate (the probability of dying between birth and age 5 y, also denoted in the literature as U5MR and (5)q(0)) is a key indicator of child health, but it conceals important information about how this mortality is distributed by age. One important distinction is what amount of the under-five mortality occurs below age 1 y ((1)q(0)) versus at age 1 y and above ((4)q(1)). However, in many country settings, this distinction is often difficult to establish because of various types of data errors. As a result, it is common practice to resort to model age patterns to estimate (1)q(0) and (4)q(1) on the basis of an observed value of (5)q(0). The most commonly used model age patterns for this purpose are the Coale and Demeny and the United Nations systems. Since the development of these models, many additional sources of data for under-five mortality have become available, making possible a general evaluation of age patterns of infant and child mortality. In this paper, we do a systematic comparison of empirical values of (1)q(0) and (4)q(1) against model age patterns, and discuss whether observed deviations are due to data errors, or whether they reflect true epidemiological patterns not addressed in existing model life tables.

RESULTS

We used vital registration data from the Human Mortality Database, sample survey data from the World Fertility Survey and Demographic and Health Surveys programs, and data from Demographic Surveillance Systems. For each of these data sources, we compared empirical combinations of (1)q(0) and (4)q(1) against combinations provided by Coale and Demeny and United Nations model age patterns. We found that, on the whole, empirical values fall relatively well within the range provided by these models, but we also found important exceptions. Sub-Saharan African countries have a tendency to exhibit high values of (4)q(1) relative to (1)q(0), a pattern that appears to arise for the most part from true epidemiological causes. While this pattern is well known in the case of western Africa, we observed that it is more widespread than commonly thought. We also found that the emergence of HIV/AIDS, while perhaps contributing to high relative values of (4)q(1), does not appear to have substantially modified preexisting patterns. We also identified a small number of countries scattered in different parts of the world that exhibit unusually low values of (4)q(1) relative to (1)q(0), a pattern that is not likely to arise merely from data errors. Finally, we illustrate that it is relatively common for populations to experience changes in age patterns of infant and child mortality as they experience a decline in mortality.

CONCLUSIONS

Existing models do not appear to cover the entire range of epidemiological situations and trajectories. Therefore, model life tables should be used with caution for estimating (1)q(0) and (4)q(1) on the basis of (5)q(0). Moreover, this model-based estimation procedure assumes that the input value of (5)q(0) is correct, which may not always be warranted, especially in the case of survey data. A systematic evaluation of data errors in sample surveys and their impact on age patterns of (1)q(0) and (4)q(1) is urgently needed, along with the development of model age patterns of under-five mortality that would cover a wider range of epidemiological situations and trajectories. Please see later in the article for the Editors' Summary.

Throughout the body, T cells monitor MHC-bound ligands expressed on the surface of essentially all cell types. MHC ligands that trigger a T cell immune response are referred to as T cell epitopes. Identifying such epitopes enables tracking, phenotyping, and stimulating T cells involved in immune responses in infectious disease, allergy, autoimmunity, transplantation, and cancer. The specific T cell epitopes recognized in an individual are determined by genetic factors such as the MHC molecules the individual expresses, in parallel to the individual's environmental exposure history. The complexity and importance of T cell epitope mapping has motivated the development of computational approaches that predict what T cell epitopes are likely to be recognized in a given individual or in a broader population. Such predictions guide experimental epitope mapping studies and enable computational analysis of the immunogenic potential of a given protein sequence region. Expected final online publication date for the Annual Review of Immunology, Volume 38 is April 26, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Legionella species are environmental gram-negative bacteria able to cause a severe form of pneumonia in humans known as Legionnaires' disease. Since the identification of Legionella pneumophila in 1977, four decades of research on Legionella biology and Legionnaires' disease have brought important insights into the biology of the bacteria and the molecular mechanisms that these intracellular pathogens use to cause disease in humans. Nowadays, Legionella species constitute a remarkable model of bacterial adaptation, with a genus genome shaped by their close coevolution with amoebae and an ability to exploit many hosts and signaling pathways through the secretion of a myriad of effector proteins, many of which have a eukaryotic origin. This review aims to discuss current knowledge of Legionella infection mechanisms and future research directions to be taken that might answer the many remaining open questions. This research will without a doubt be a terrific scientific journey worth taking. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 15 is January 24, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Guided by its sight, scent, texture, and taste, animals ingest food. Once ingested, it is up to the gut to make sense of the food's nutritional value. Classic sensory systems rely on neuroepithelial circuits to convert stimuli into signals that guide behavior. However, sensation of the gut milieu was thought to be mediated only by the passive release of hormones until the discovery of synapses in enteroendocrine cells. These are gut sensory epithelial cells, and those that form synapses are referred as neuropod cells. Neuropod cells provide the foundation for the gut to transduce sensory signals from the intestinal milieu to the brain through fast neurotransmission onto neurons, including those of the vagus nerve. These findings have sparked a new field of exploration in sensory neurobiology-that of gut-brain sensory transduction. Expected final online publication date for the Annual Review of Neuroscience, Volume 43 is July 8, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Visual categories group together different objects as the same kinds of thing. We review a selection of research on how visual categories are learned. We begin with a guide to visual category learning experiments, describing a space of common manipulations of objects, categories, and methods used in the category learning literature. We open with a guide to these details in part because throughout our review we highlight how methodological details can sometimes loom large in theoretical discussions of visual category learning, how variations in methodological details can significantly affect our understanding of visual category learning, and how manipulations of methodological details can affect how visual categories are learned. We review a number of core theories of visual category learning, specifically those theories instantiated as computational models, highlighting just some of the experimental results that help distinguish between competing models. We examine behavioral and neural evidence for single versus multiple representational systems for visual category learning. We briefly discuss how visual category learning influences visual perception, describing empirical and brain imaging results that show how learning to categorize objects can influence how those objects are represented and perceived. We close with work that can potentially impact translation, describing recent experiments that explicitly manipulate key methodological details of category learning procedures with the goal of optimizing visual category learning. WIREs Cogn Sci 2014, 5:75-94. doi: 10.1002/wcs.1268 CONFLICT OF INTEREST: The authors have declared no conflicts of interest for this article. For further resources related to this article, please visit the WIREs website.

Inductive reasoning entails using existing knowledge or observations to make predictions about novel cases. We review recent findings in research on category-based induction as well as theoretical models of these results, including similarity-based models, connectionist networks, an account based on relevance theory, Bayesian models, and other mathematical models. A number of touchstone empirical phenomena that involve taxonomic similarity are described. We also examine phenomena involving more complex background knowledge about premises and conclusions of inductive arguments and the properties referenced. Earlier models are shown to give a good account of similarity-based phenomena but not knowledge-based phenomena. Recent models that aim to account for both similarity-based and knowledge-based phenomena are reviewed and evaluated. Among the most important new directions in induction research are a focus on induction with uncertain premise categories, the modeling of the relationship between inductive and deductive reasoning, and examination of the neural substrates of induction. A common theme in both the well-established and emerging lines of induction research is the need to develop well-articulated and empirically testable formal models of induction. Copyright © 2010 John Wiley & Sons, Ltd. For further resources related to this article, please visit the WIREs website.