BACKGROUND

Information about the distribution of causes of and time trends for child mortality should be periodically updated. We report the latest estimates of causes of child mortality in 2010 with time trends since 2000.

METHODS

Updated total numbers of deaths in children aged 0-27 days and 1-59 months were applied to the corresponding country-specific distribution of deaths by cause. We did the following to derive the number of deaths in children aged 1-59 months: we used vital registration data for countries with an adequate vital registration system; we applied a multinomial logistic regression model to vital registration data for low-mortality countries without adequate vital registration; we used a similar multinomial logistic regression with verbal autopsy data for high-mortality countries; for India and China, we developed national models. We aggregated country results to generate regional and global estimates.

RESULTS

Of 7·6 million deaths in children younger than 5 years in 2010, 64·0% (4·879 million) were attributable to infectious causes and 40·3% (3·072 million) occurred in neonates. Preterm birth complications (14·1%; 1·078 million, uncertainty range [UR] 0·916-1·325), intrapartum-related complications (9·4%; 0·717 million, 0·610-0·876), and sepsis or meningitis (5·2%; 0·393 million, 0·252-0·552) were the leading causes of neonatal death. In older children, pneumonia (14·1%; 1·071 million, 0·977-1·176), diarrhoea (9·9%; 0·751 million, 0·538-1·031), and malaria (7·4%; 0·564 million, 0·432-0·709) claimed the most lives. Despite tremendous efforts to identify relevant data, the causes of only 2·7% (0·205 million) of deaths in children younger than 5 years were medically certified in 2010. Between 2000 and 2010, the global burden of deaths in children younger than 5 years decreased by 2 million, of which pneumonia, measles, and diarrhoea contributed the most to the overall reduction (0·451 million [0·339-0·547], 0·363 million [0·283-0·419], and 0·359 million [0·215-0·476], respectively). However, only tetanus, measles, AIDS, and malaria (in Africa) decreased at an annual rate sufficient to attain the Millennium Development Goal 4.

CONCLUSIONS

Child survival strategies should direct resources toward the leading causes of child mortality, with attention focusing on infectious and neonatal causes. More rapid decreases from 2010-15 will need accelerated reduction for the most common causes of death, notably pneumonia and preterm birth complications. Continued efforts to gather high-quality data and enhance estimation methods are essential for the improvement of future estimates.

BACKGROUND

The Bill & Melinda Gates Foundation.

Attention deficit hyperactivity disorder (ADHD) comprises a deficit in behavioral inhibition. A theoretical model is constructed that links inhibition to 4 executive neuropsychological functions that appear to depend on it for their effective execution: (a) working memory, (b) self-regulation of affect-motivation-arousal, (c) internalization of speech, and (d) reconstitution (behavioral analysis and synthesis). Extended to ADHD, the model predicts that ADHD should be associated with secondary impairments in these 4 executive abilities and the motor control they afford. The author reviews evidence for each of these domains of functioning and finds it to be strongest for deficits in behavioral inhibition, working memory, regulation of motivation, and motor control in those with ADHD. Although the model is promising as a potential theory of self-control and ADHD, far more research is required to evaluate its merits and the many predictions it makes about ADHD.

The functional relationship between apoptosis ('self-killing') and autophagy ('self-eating') is complex in the sense that, under certain circumstances, autophagy constitutes a stress adaptation that avoids cell death (and suppresses apoptosis), whereas in other cellular settings, it constitutes an alternative cell-death pathway. Autophagy and apoptosis may be triggered by common upstream signals, and sometimes this results in combined autophagy and apoptosis; in other instances, the cell switches between the two responses in a mutually exclusive manner. On a molecular level, this means that the apoptotic and autophagic response machineries share common pathways that either link or polarize the cellular responses.

The Dual Organellar GenoMe Annotator (DOGMA) automates the annotation of organellar (plant chloroplast and animal mitochondrial) genomes. It is a Web-based package that allows the use of BLAST searches against a custom database, and conservation of basepairing in the secondary structure of animal mitochondrial tRNAs to identify and annotate genes. DOGMA provides a graphical user interface for viewing and editing annotations. Annotations are stored on our password-protected server to enable repeated sessions of working on the same genome. Finished annotations can be extracted for direct submission to GenBank.

BACKGROUND

The Nearest Alignment Space Termination (NAST) tool is commonly used in sequence-based microbial ecology community analysis, but due to the limited portability of the original implementation, it has not been as widely adopted as possible. Python Nearest Alignment Space Termination (PyNAST) is a complete reimplementation of NAST, which includes three convenient interfaces: a Mac OS X GUI, a command-line interface and a simple application programming interface (API).

RESULTS

The availability of PyNAST will make the popular NAST algorithm more portable and thereby applicable to datasets orders of magnitude larger by allowing users to install PyNAST on their own hardware. Additionally because users can align to arbitrary template alignments, a feature not available via the original NAST web interface, the NAST algorithm will be readily applicable to novel tasks outside of microbial community analysis.

BACKGROUND

PyNAST is available at http://pynast.sourceforge.net.

Chromatin is not an inert structure, but rather an instructive DNA scaffold that can respond to external cues to regulate the many uses of DNA. A principle component of chromatin that plays a key role in this regulation is the modification of histones. There is an ever-growing list of these modifications and the complexity of their action is only just beginning to be understood. However, it is clear that histone modifications play fundamental roles in most biological processes that are involved in the manipulation and expression of DNA. Here, we describe the known histone modifications, define where they are found genomically and discuss some of their functional consequences, concentrating mostly on transcription where the majority of characterisation has taken place.

KEGG (http://www.kegg.jp/ or http://www.genome.jp/kegg/) is an integrated database resource for biological interpretation of genome sequences and other high-throughput data. Molecular functions of genes and proteins are associated with ortholog groups and stored in the KEGG Orthology (KO) database. The KEGG pathway maps, BRITE hierarchies and KEGG modules are developed as networks of KO nodes, representing high-level functions of the cell and the organism. Currently, more than 4000 complete genomes are annotated with KOs in the KEGG GENES database, which can be used as a reference data set for KO assignment and subsequent reconstruction of KEGG pathways and other molecular networks. As an annotation resource, the following improvements have been made. First, each KO record is re-examined and associated with protein sequence data used in experiments of functional characterization. Second, the GENES database now includes viruses, plasmids, and the addendum category for functionally characterized proteins that are not represented in complete genomes. Third, new automatic annotation servers, BlastKOALA and GhostKOALA, are made available utilizing the non-redundant pangenome data set generated from the GENES database. As a resource for translational bioinformatics, various data sets are created for antimicrobial resistance and drug interaction networks.

The effect of various drugs on the extracellular concentration of dopamine in two terminal dopaminergic areas, the nucleus accumbens septi (a limbic area) and the dorsal caudate nucleus (a subcortical motor area), was studied in freely moving rats by using brain dialysis. Drugs abused by humans (e.g., opiates, ethanol, nicotine, amphetamine, and cocaine) increased extracellular dopamine concentrations in both areas, but especially in the accumbens, and elicited hypermotility at low doses. On the other hand, drugs with aversive properties (e.g., agonists of kappa opioid receptors, U-50,488, tifluadom, and bremazocine) reduced dopamine release in the accumbens and in the caudate and elicited hypomotility. Haloperidol, a neuroleptic drug, increased extracellular dopamine concentrations, but this effect was not preferential for the accumbens and was associated with hypomotility and sedation. Drugs not abused by humans [e.g., imipramine (an antidepressant), atropine (an antimuscarinic drug), and diphenhydramine (an antihistamine)] failed to modify synaptic dopamine concentrations. These results provide biochemical evidence for the hypothesis that stimulation of dopamine transmission in the limbic system might be a fundamental property of drugs that are abused.

The Infectious Diseases Society of America (IDSA) continues to view with concern the lean pipeline for novel therapeutics to treat drug-resistant infections, especially those caused by gram-negative pathogens. Infections now occur that are resistant to all current antibacterial options. Although the IDSA is encouraged by the prospect of success for some agents currently in preclinical development, there is an urgent, immediate need for new agents with activity against these panresistant organisms. There is no evidence that this need will be met in the foreseeable future. Furthermore, we remain concerned that the infrastructure for discovering and developing new antibacterials continues to stagnate, thereby risking the future pipeline of antibacterial drugs. The IDSA proposed solutions in its 2004 policy report, "Bad Bugs, No Drugs: As Antibiotic R&D Stagnates, a Public Health Crisis Brews," and recently issued a "Call to Action" to provide an update on the scope of the problem and the proposed solutions. A primary objective of these periodic reports is to encourage a community and legislative response to establish greater financial parity between the antimicrobial development and the development of other drugs. Although recent actions of the Food and Drug Administration and the 110th US Congress present a glimmer of hope, significant uncertainly remains. Now, more than ever, it is essential to create a robust and sustainable antibacterial research and development infrastructure--one that can respond to current antibacterial resistance now and anticipate evolving resistance. This challenge requires that industry, academia, the National Institutes of Health, the Food and Drug Administration, the Centers for Disease Control and Prevention, the US Department of Defense, and the new Biomedical Advanced Research and Development Authority at the Department of Health and Human Services work productively together. This report provides an update on potentially effective antibacterial drugs in the late-stage development pipeline, in the hope of encouraging such collaborative action.

A purified protein derived from the twisted beta-pleated sheet fibrils in cerebrovascular amyloidosis associated with Alzheimer's disease has been isolated by Sephadex G-100 column chromatography with 5 M guanidine-HC1 in 1 N acetic acid and by high performance liquid chromatography. Amino acid sequence analysis and a computer search reveals this protein to have no homology with any protein sequenced thus far. This protein may be derived from a unique serum precursor which may provide a diagnostic test for Alzheimer's disease and a means to understand its pathogenesis.

Diagnostic systems of several kinds are used to distinguish between two classes of events, essentially "signals" and "noise". For them, analysis in terms of the "relative operating characteristic" of signal detection theory provides a precise and valid measure of diagnostic accuracy. It is the only measure available that is uninfluenced by decision biases and prior probabilities, and it places the performances of diverse systems on a common, easily interpreted scale. Representative values of this measure are reported here for systems in medical imaging, materials testing, weather forecasting, information retrieval, polygraph lie detection, and aptitude testing. Though the measure itself is sound, the values obtained from tests of diagnostic systems often require qualification because the test data on which they are based are of unsure quality. A common set of problems in testing is faced in all fields. How well these problems are handled, or can be handled in a given field, determines the degree of confidence that can be placed in a measured value of accuracy. Some fields fare much better than others.

OBJECTIVE

To describe the National Institute of Mental Health Diagnostic Interview Schedule for Children Version IV (NIMH DISC-IV) and how it differs from earlier versions of the interview. The NIMH DISC-IV is a highly structured diagnostic interview, designed to assess more than 30 psychiatric disorders occurring in children and adolescents, and can be administered by "lay" interviewers after a minimal training period. The interview is available in both English and Spanish versions.

METHODS

An editorial board was established in 1992 to guide DISC development and ensure that a standard version of the instrument is maintained. Preliminary reliability and acceptability results of the NIMH DISC-IV in a clinical sample of 84 parents and 82 children (aged 9-17 years) drawn from outpatient child and adolescent psychiatric clinics at 3 sites are presented. Results of the previous version in a community sample are reviewed.

RESULTS

Despite its greater length and complexity, the NIMH DISC-IV compares favorably with earlier versions. Alternative versions of the interview are in development (the Present State DISC, the Teacher DISC, the Quick DISC, the Voice DISC).

CONCLUSIONS

The NIMH DISC is an acceptable, inexpensive, and convenient instrument for ascertaining a comprehensive range of child and adolescent diagnoses.

The reduction of oxygen to water proceeds via one electron at a time. In the mitochondrial respiratory chain, Complex IV (cytochrome oxidase) retains all partially reduced intermediates until full reduction is achieved. Other redox centres in the electron transport chain, however, may leak electrons to oxygen, partially reducing this molecule to superoxide anion (O2-*). Even though O2-* is not a strong oxidant, it is a precursor of most other reactive oxygen species, and it also becomes involved in the propagation of oxidative chain reactions. Despite the presence of various antioxidant defences, the mitochondrion appears to be the main intracellular source of these oxidants. This review describes the main mitochondrial sources of reactive species and the antioxidant defences that evolved to prevent oxidative damage in all the mitochondrial compartments. We also discuss various physiological and pathological scenarios resulting from an increased steady state concentration of mitochondrial oxidants.

The cellular constituents forming the haematopoietic stem cell (HSC) niche in the bone marrow are unclear, with studies implicating osteoblasts, endothelial and perivascular cells. Here we demonstrate that mesenchymal stem cells (MSCs), identified using nestin expression, constitute an essential HSC niche component. Nestin(+) MSCs contain all the bone-marrow colony-forming-unit fibroblastic activity and can be propagated as non-adherent 'mesenspheres' that can self-renew and expand in serial transplantations. Nestin(+) MSCs are spatially associated with HSCs and adrenergic nerve fibres, and highly express HSC maintenance genes. These genes, and others triggering osteoblastic differentiation, are selectively downregulated during enforced HSC mobilization or beta3 adrenoreceptor activation. Whereas parathormone administration doubles the number of bone marrow nestin(+) cells and favours their osteoblastic differentiation, in vivo nestin(+) cell depletion rapidly reduces HSC content in the bone marrow. Purified HSCs home near nestin(+) MSCs in the bone marrow of lethally irradiated mice, whereas in vivo nestin(+) cell depletion significantly reduces bone marrow homing of haematopoietic progenitors. These results uncover an unprecedented partnership between two distinct somatic stem-cell types and are indicative of a unique niche in the bone marrow made of heterotypic stem-cell pairs.

BACKGROUND

Constitutive activation of KIT receptor tyrosine kinase is critical in the pathogenesis of gastrointestinal stromal tumors. Imatinib mesylate, a selective tyrosine kinase inhibitor, has been shown in preclinical models and preliminary clinical studies to have activity against such tumors.

METHODS

We conducted an open-label, randomized, multicenter trial to evaluate the activity of imatinib in patients with advanced gastrointestinal stromal tumor. We assessed antitumor response and the safety and tolerability of the drug. Pharmacokinetics were assessed in a subgroup of patients.

RESULTS

A total of 147 patients were randomly assigned to receive 400 mg or 600 mg of imatinib daily. Overall, 79 patients (53.7 percent) had a partial response, 41 patients (27.9 percent) had stable disease, and for technical reasons, response could not be evaluated in 7 patients (4.8 percent). No patient had a complete response to the treatment. The median duration of response had not been reached after a median follow-up of 24 weeks after the onset of response. Early resistance to imatinib was noted in 20 patients (13.6 percent). Therapy was well tolerated, although mild-to-moderate edema, diarrhea, and fatigue were common. Gastrointestinal or intraabdominal hemorrhage occurred in approximately 5 percent of patients. There were no significant differences in toxic effects or response between the two doses. Imatinib was well absorbed, with pharmacokinetics similar to those reported in patients with chronic myeloid leukemia.

CONCLUSIONS

Imatinib induced a sustained objective response in more than half of patients with an advanced unresectable or metastatic gastrointestinal stromal tumor. Inhibition of the KIT signal-transduction pathway is a promising treatment for advanced gastrointestinal stromal tumors, which resist conventional chemotherapy.

The Cowan I strain of the bacterium Staphylococcus aureus has been used as an adsorbent for antibodies complexed with radiolabeled antigens from cell lysates. This application is advanced as a superior alternative to other methods of immune precipitation for the isolation of antigens. It exploits the high adsorption capacity for IgG molecules by protein A molecules on the cell walls of certain strains of staphylococci, along with the advantageous sedimentation properties of the bacteria. The interaction of immune complexes with the adsorbent was defined initially using a model system of bovine serum albumin with a high excess of rabbit anti-bovine serum albumin antibodies (IgG). The uptake of immune complexes under these conditions was extremely rapid, occurring within seconds, whereas maximum binding of free IgG was much slower. In addition, once bound the complexed antigen could not be displaced from the adsorbent either by large amounts of normal IgG or by extra free antibody. Antigen could be eluted almost completely from the inert adsorbent for analytic or preparative purposes with a variety of solvent systems, such as the detergent SDS in combination with urea and high temperature, and neutral salts with strong lyotropic salting in properties. The efficacy of the protein A-antibody adsorption technique was tested in direct comparisons with a conventional double antibody precipitation method for the isolation of mouse lymphocyte IgM. The bacterial adsorbent not only had a distinct advantage in speed of antigen isolation, but analyses by polyacrylamide gel electrophoresis in SDS also revealed consistently higher antigen recoveries, lower levels of background radioactivity, and an absence of other cell components which may nonspecifically bind to and complicate analyses using conventional immune precipitates.

Gene conversion is the nonreciprocal transfer of information from one DNA duplex to another; in meiosis, it is frequently associated with crossing-over. We review the genetic properties of meiotic recombination and previous models of conversion and crossing-over. In these models, recombination is initiated by single-strand nicks, and heteroduplex DNA is generated. Gene conversion is explained by the repair of mismatches present in heteroduplex DNA. We propose a new mechanism for meiotic recombination, in which events are initiated by double-strand breaks that are enlarged to double-strand gaps. Gene conversion can then occur by the repair of a double-strand gap, and postmeiotic segregation can result from heteroduplex DNA formed at the boundaries of the gap-repair region. The repair of double-strand gaps is an efficient process in yeast, and is known to be associated with crossing-over. The genetic implications of the double-strand-break repair model are explored.

BACKGROUND

Infection with Helicobacter pylori has been linked with chronic atrophic gastritis, an inflammatory precursor of gastric adenocarcinoma. In a nested case-control study, we explored whether H. pylori infection increases the risk of gastric carcinoma.

METHODS

From a cohort of 128,992 persons followed since the mid-1960s at a health maintenance organization, 186 patients with gastric carcinoma were selected as case patients and were matched according to age, sex, and race with 186 control subjects without gastric carcinoma. Stored serum samples collected during the 1960s were tested for IgG antibodies to H. pylori by enzyme-linked immunosorbent assay. Data on cigarette use, blood group, ulcer disease, and gastric surgery were obtained from questionnaires administered at enrollment. Tissue sections and pathology reports were reviewed to confirm the histologic results.

RESULTS

The mean time between serum collection and the diagnosis of gastric carcinoma was 14.2 years. Of the 109 patients with confirmed gastric adenocarcinoma (excluding tumors of the gastroesophageal junction), 84 percent had been infected previously with H. pylori, as compared with 61 percent of the matched control subjects (odds ratio, 3.6; 95 percent confidence interval, 1.8 to 7.3). Tumors of the gastroesophageal junction were not linked to H. pylori infection, nor were tumors in the gastric cardia. H. pylori was a particularly strong risk factor for stomach cancer in women (odds ratio, 18) and blacks (odds ratio, 9). A history of gastric surgery was independently associated with the development of cancer (odds ratio, 17; P = 0.03), but a history of peptic ulcer disease was negatively associated with subsequent gastric carcinoma (odds ratio, 0.2; P = 0.02). Neither blood group nor smoking history affected risk.

CONCLUSIONS

Infection with H. pylori is associated with an increased risk of gastric adenocarcinoma and may be a cofactor in the pathogenesis of this malignant condition.

BACKGROUND

A worldwide outbreak of severe acute respiratory syndrome (SARS) has been associated with exposures originating from a single ill health care worker from Guangdong Province, China. We conducted studies to identify the etiologic agent of this outbreak.

METHODS

We received clinical specimens from patients in seven countries and tested them, using virus-isolation techniques, electron-microscopical and histologic studies, and molecular and serologic assays, in an attempt to identify a wide range of potential pathogens.

RESULTS

None of the previously described respiratory pathogens were consistently identified. However, a novel coronavirus was isolated from patients who met the case definition of SARS. Cytopathological features were noted in Vero E6 cells inoculated with a throat-swab specimen. Electron-microscopical examination revealed ultrastructural features characteristic of coronaviruses. Immunohistochemical and immunofluorescence staining revealed reactivity with group I coronavirus polyclonal antibodies. Consensus coronavirus primers designed to amplify a fragment of the polymerase gene by reverse transcription-polymerase chain reaction (RT-PCR) were used to obtain a sequence that clearly identified the isolate as a unique coronavirus only distantly related to previously sequenced coronaviruses. With specific diagnostic RT-PCR primers we identified several identical nucleotide sequences in 12 patients from several locations, a finding consistent with a point-source outbreak. Indirect fluorescence antibody tests and enzyme-linked immunosorbent assays made with the new isolate have been used to demonstrate a virus-specific serologic response. This virus may never before have circulated in the U.S. population.

CONCLUSIONS

A novel coronavirus is associated with this outbreak, and the evidence indicates that this virus has an etiologic role in SARS. Because of the death of Dr. Carlo Urbani, we propose that our first isolate be named the Urbani strain of SARS-associated coronavirus.

Whether and how human tumours are genetically unstable has been debated for decades. There is now evidence that most cancers may indeed be genetically unstable, but that the instability exists at two distinct levels. In a small subset of tumours, the instability is observed at the nucleotide level and results in base substitutions or deletions or insertions of a few nucleotides. In most other cancers, the instability is observed at the chromosome level, resulting in losses and gains of whole chromosomes or large portions thereof. Recognition and comparison of these instabilities are leading to new insights into tumour pathogenesis.

Homeostatic model assessment (HOMA) is a method for assessing beta-cell function and insulin resistance (IR) from basal (fasting) glucose and insulin or C-peptide concentrations. It has been reported in >500 publications, 20 times more frequently for the estimation of IR than beta-cell function. This article summarizes the physiological basis of HOMA, a structural model of steady-state insulin and glucose domains, constructed from physiological dose responses of glucose uptake and insulin production. Hepatic and peripheral glucose efflux and uptake were modeled to be dependent on plasma glucose and insulin concentrations. Decreases in beta-cell function were modeled by changing the beta-cell response to plasma glucose concentrations. The original HOMA model was described in 1985 with a formula for approximate estimation. The computer model is available but has not been as widely used as the approximation formulae. HOMA has been validated against a variety of physiological methods. We review the use and reporting of HOMA in the literature and give guidance on its appropriate use (e.g., cohort and epidemiological studies) and inappropriate use (e.g., measuring beta-cell function in isolation). The HOMA model compares favorably with other models and has the advantage of requiring only a single plasma sample assayed for insulin and glucose. In conclusion, the HOMA model has become a widely used clinical and epidemiological tool and, when used appropriately, it can yield valuable data. However, as with all models, the primary input data need to be robust, and the data need to be interpreted carefully.

CONCLUSIONS

Here, we present PRINSEQ for easy and rapid quality control and data preprocessing of genomic and metagenomic datasets. Summary statistics of FASTA (and QUAL) or FASTQ files are generated in tabular and graphical form and sequences can be filtered, reformatted and trimmed by a variety of options to improve downstream analysis.

METHODS

This open-source application was implemented in Perl and can be used as a stand alone version or accessed online through a user-friendly web interface. The source code, user help and additional information are available at http://prinseq.sourceforge.net/.

Procedures are described for the detection and isolation of plasmids of various sizes (2.6 to 350 megadaltons) that are harbored in species of Agrobacterium, Rhizobium, Escherichia, Salmonella, Erwinia, Pseudomonas, and Xanthomonas. The method utilized the molecular characteristics of covalently closed circular deoxyribonucleic acid (DNA) that is released from cells under conditions that denature chromosomal DNA by using alkaline sodium dodecyl sulfate (pH 12.6) at elevated temperatures. Proteins and cell debris were removed by extraction with phenol-chloroform. Under these conditions chromosomal DNA concentrations were reduced or eliminated. The clarified extract was used directly for electrophoretic analysis. These procedures also permitted the selective isolation of plasmid DNA that can be used directly in nick translation, restriction endonuclease analysis, transformation, and DNA cloning experiments.

A multilocus sequence typing (MLST) scheme has been developed for Staphylococcus aureus. The sequences of internal fragments of seven housekeeping genes were obtained for 155 S. aureus isolates from patients with community-acquired and hospital-acquired invasive disease in the Oxford, United Kingdom, area. Fifty-three different allelic profiles were identified, and 17 of these were represented by at least two isolates. The MLST scheme was highly discriminatory and was validated by showing that pairs of isolates with the same allelic profile produced very similar SmaI restriction fragment patterns by pulsed-field gel electrophoresis. All 22 isolates with the most prevalent allelic profile were methicillin-resistant S. aureus (MRSA) isolates and had allelic profiles identical to that of a reference strain of the epidemic MRSA clone 16 (EMRSA-16). Four MRSA isolates that were identical in allelic profile to the other major epidemic MRSA clone prevalent in British hospitals (clone EMRSA-15) were also identified. The majority of isolates (81%) were methicillin-susceptible S. aureus (MSSA) isolates, and seven MSSA clones included five or more isolates. Three of the MSSA clones included at least five isolates from patients with community-acquired invasive disease and may represent virulent clones with an increased ability to cause disease in otherwise healthy individuals. The most prevalent MSSA clone (17 isolates) was very closely related to EMRSA-16, and the success of the latter clone at causing disease in hospitals may be due to its emergence from a virulent MSSA clone that was already a major cause of invasive disease in both the community and hospital settings. MLST provides an unambiguous method for assigning MRSA and MSSA isolates to known clones or assigning them as novel clones via the Internet.