Frequency-dependent selection in vaccine-associated pneumococcal population dynamics

Many bacterial species are composed of multiple lineages distinguished by extensive variation in gene content. These often cocirculate in the same habitat, but the evolutionary and ecological processes that shape these complex populations are poorly understood. Addressing these questions is particularly important for Streptococcus pneumoniae, a nasopharyngeal commensal and respiratory pathogen, because the changes in population structure associated with the recent introduction of partial-coverage vaccines have substantially reduced pneumococcal disease. Here we show that pneumococcal lineages from multiple populations each have a distinct combination of intermediate-frequency genes. Functional analysis suggested that these loci may be subject to negative frequency-dependent selection (NFDS) through interactions with other bacteria, hosts or mobile elements. Correspondingly, these genes had similar frequencies in four populations with dissimilar lineage compositions. These frequencies were maintained following substantial alterations in lineage prevalences once vaccination programmes began. Fitting a multilocus NFDS model of post-vaccine population dynamics to three genomic datasets using Approximate Bayesian Computation generated reproducible estimates of the influence of NFDS on pneumococcal evolution, the strength of which varied between loci. Simulations replicated the stable frequency of lineages unperturbed by vaccination, patterns of serotype switching and clonal replacement. This framework highlights how bacterial ecology affects the impact of clinical interventions.Accessory loci are shown to have similar frequencies in diverse Streptococcus pneumoniae populations, suggesting negative frequency-dependent selection drives post-vaccination population restructuring

Differences in genotype and virulence among four multidrug-resistant <i>Streptococcus pneumoniae</i> isolates belonging to the PMEN1 clone

We report on the comparative genomics and characterization of the virulence phenotypes of four &lt;i&gt;S. pneumoniae&lt;/i&gt; strains that belong to the multidrug resistant clone PMEN1 (Spain&lt;sup&gt;23F&lt;/sup&gt; ST81). Strains SV35-T23 and SV36-T3 were recovered in 1996 from the nasopharynx of patients at an AIDS hospice in New York. Strain SV36-T3 expressed capsule type 3 which is unusual for this clone and represents the product of an in vivo capsular switch event. A third PMEN1 isolate - PN4595-T23 - was recovered in 1996 from the nasopharynx of a child attending day care in Portugal, and a fourth strain - ATCC700669 - was originally isolated from a patient with pneumococcal disease in Spain in 1984. We compared the genomes among four PMEN1 strains and 47 previously sequenced pneumococcal isolates for gene possession differences and allelic variations within core genes. In contrast to the 47 strains - representing a variety of clonal types - the four PMEN1 strains grouped closely together, demonstrating high genomic conservation within this lineage relative to the rest of the species. In the four PMEN1 strains allelic and gene possession differences were clustered into 18 genomic regions including the capsule, the blp bacteriocins, erythromycin resistance, the MM1-2008 prophage and multiple cell wall anchored proteins. In spite of their genomic similarity, the high resolution chinchilla model was able to detect variations in virulence properties of the PMEN1 strains highlighting how small genic or allelic variation can lead to significant changes in pathogenicity and making this set of strains ideal for the identification of novel virulence determinant

MRI of the lung (3/3)-current applications and future perspectives

BACKGROUND: MRI of the lung is recommended in a number of clinical indications. Having a non-radiation alternative is particularly attractive in children and young subjects, or pregnant women. METHODS: Provided there is sufficient expertise, magnetic resonance imaging (MRI) may be considered as the preferential modality in specific clinical conditions such as cystic fibrosis and acute pulmonary embolism, since additional functional information on respiratory mechanics and regional lung perfusion is provided. In other cases, such as tumours and pneumonia in children, lung MRI may be considered an alternative or adjunct to other modalities with at least similar diagnostic value. RESULTS: In interstitial lung disease, the clinical utility of MRI remains to be proven, but it could provide additional information that will be beneficial in research, or at some stage in clinical practice. Customised protocols for chest imaging combine fast breath-hold acquisitions from a "buffet" of sequences. Having introduced details of imaging protocols in previous articles, the aim of this manuscript is to discuss the advantages and limitations of lung MRI in current clinical practice. CONCLUSION: New developments and future perspectives such as motion-compensated imaging with self-navigated sequences or fast Fourier decomposition MRI for non-contrast enhanced ventilation- and perfusion-weighted imaging of the lung are discussed. Main Messages • MRI evolves as a third lung imaging modality, combining morphological and functional information. • It may be considered first choice in cystic fibrosis and pulmonary embolism of young and pregnant patients. • In other cases (tumours, pneumonia in children), it is an alternative or adjunct to X-ray and CT. • In interstitial lung disease, it serves for research, but the clinical value remains to be proven. • New users are advised to make themselves familiar with the particular advantages and limitations

An Educational and Physical Program to Reduce Headache, Neck/Shoulder Pain in a Working Community: A Cluster-Randomized Controlled Trial

Background: Noninvasive physical management is often prescribed for headache and neck pain. Systematic reviews, however, indicate that the evidence of its efficacy is limited. Our aim was to evaluate the effectiveness of a workplace educational and physical program in reducing headache and neck/shoulder pain. Methodology/Principal Findings: Cluster-randomized controlled trial. All municipal workers of the City of Turin, Italy, were invited to participate. Those who agreed were randomly assigned, according to their departments, to the intervention group (IG) or to the control group and were given diaries for the daily recording of pain episodes for 1 month (baseline). Subsequently, only the IG (119 departments, 923 workers) began the physical and educational program, whereas the control group (117 departments, 990 workers) did not receive any intervention. All participants were again given diaries for the daily recording of pain episodes after 6 months of intervention. The primary outcome was the change in the frequency of headache (expressed as the proportion of subjects with a 6550% reduction of frequency; responder rate); among the secondary outcomes there were the absolute reduction of the number of days per month with headache and neck/shoulder pain. Differences between the two groups were evaluated using mixed-effect regression models. The IG showed a higher responder rate [risk ratio, 95% confidence interval (CI)] for headache (1.58; 1.28 to 1.92) and for neck/shoulder pain (1.53; 1.27 to 1.82), and a larger reduction of the days per month (95% CI) with headache (-1.72; -2.40 to -1.04) and with neck/shoulder pain (-2.51; -3.56 to -1.47). Conclusions: The program effectively reduced headache and neck/shoulder pain in a large working community and appears to be easily transferable to primary-care settings. Further trials are needed to investigate the program effectiveness in a clinical setting, for highly selected patients suffering from specific headache types. Trial Registration: ClinicalTrials.gov NCT00551980. \ua9 2012 Mongini et al

Genomic fluidity: an integrative view of gene diversity within microbial populations

<p>Abstract</p> <p>Background</p> <p>The dual concepts of pan and core genomes have been widely adopted as means to assess the distribution of gene families within microbial species and genera. The core genome is the set of genes shared by a group of organisms; the pan genome is the set of all genes seen in any of these organisms. A variety of methods have provided drastically different estimates of the sizes of pan and core genomes from sequenced representatives of the same groups of bacteria.</p> <p>Results</p> <p>We use a combination of mathematical, statistical and computational methods to show that current predictions of pan and core genome sizes may have no correspondence to true values. Pan and core genome size estimates are problematic because they depend on the estimation of the occurrence of rare genes and genomes, respectively, which are difficult to estimate precisely because they are rare. Instead, we introduce and evaluate a robust metric - genomic fluidity - to categorize the gene-level similarity among groups of sequenced isolates. Genomic fluidity is a measure of the dissimilarity of genomes evaluated at the gene level.</p> <p>Conclusions</p> <p>The genomic fluidity of a population can be estimated accurately given a small number of sequenced genomes. Further, the genomic fluidity of groups of organisms can be compared robustly despite variation in algorithms used to identify genes and their homologs. As such, we recommend that genomic fluidity be used in place of pan and core genome size estimates when assessing gene diversity within genomes of a species or a group of closely related organisms.</p

The long-term effects of naprapathic manual therapy on back and neck pain - Results from a pragmatic randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Back and neck pain are very common, disabling and recurrent disorders in the general population and the knowledge of long-term effect of treatments are sparse. The aim of this study was to compare the long-term effects (up to one year) of naprapathic manual therapy and evidence-based advice on staying active regarding non-specific back and/or neck pain. Naprapathy, a health profession mainly practiced in Sweden, Finland, Norway and in the USA, is characterized by a combination of manual musculoskeletal manipulations, aiming to decrease pain and disability in the neuromusculoskeletal system.</p> <p>Methods</p> <p>Subjects with non-specific pain/disability in the back and/or neck lasting for at least two weeks (n = 409), recruited at public companies in Sweden, were included in this pragmatic randomized controlled trial. The two interventions compared were naprapathic manual therapy such as spinal manipulation/mobilization, massage and stretching, (<it>Index Group</it>), and advice to stay active and on how to cope with pain, provided by a physician (C<it>ontrol Group</it>). Pain intensity, disability and health status were measured by questionnaires.</p> <p>Results</p> <p>89% completed the 26-week follow-up and 85% the 52-week follow-up. A higher proportion in the Index Group had a clinically important decrease in pain (risk difference (RD) = 21%, <it>95% CI: 10-30</it>) and disability (RD = 11%, <it>95% CI: 4-22</it>) at 26-week, as well as at 52-week follow-ups (pain: RD = 17%, <it>95% CI: 7-27 </it>and disability: RD = 17%, <it>95% CI: 5-28</it>). The differences between the groups in pain and disability considered over one year were statistically significant favoring naprapathy (p ≤ 0.005). There were also significant differences in improvement in bodily pain and social function (subscales of SF-36 health status) favoring the Index Group.</p> <p>Conclusions</p> <p>Combined manual therapy, like naprapathy, is effective in the short and in the long term, and might be considered for patients with non-specific back and/or neck pain.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN56954776.</p

Incidence and determinants of new AIDS-defining illnesses after HAART initiation in a Senegalese cohort

<p>Abstract</p> <p>Background</p> <p>Although a dramatic decrease in AIDS progression has been observed after Highly Active Anti Retroviral Therapy (HAART) in both low- and high-resource settings, few data support that fact in low-resource settings.</p> <p>This study describes the incidence of AIDS-defining illnesses (ADI) after HAART initiation and analyzes their risk factors in a low-resource setting. A focus was put on CD4 cell counts and viral load measurements.</p> <p>Methods</p> <p>404 HIV-1-infected Senegalese adult patients were enrolled in a prospective observational cohort and data censored as of April 2008. A Poisson regression was used to model the incidence of ADIs over two periods and to assess its association with baseline variables, current CD4, current viral load, CD4 response, and virological response.</p> <p>Results</p> <p>ADI incidence declined from 20.5 ADIs per 100 person-years, 95% CI = [16.3;25.8] during the first year to 4.3, 95% CI = [2.3;8.1] during the fourth year but increased afterwards. Before 42 months, the decrease was greater in patients with clinical stage CDC-C at baseline and with a viral load remaining below 1000 cp/mL but was uniform across CD4 strata (p = 0.1). After 42 months, 293 patients were still at risk. The current CD4 and viral load were associated with ADI incidence (decrease of 21% per 50 CD4/mm³and of 61% for patients with a viral load < 1000 cp/mL).</p> <p>Conclusions</p> <p>During the first four years, a uniform decline of ADI incidence was observed even in patients with low CD4-cell counts at HAART initiation as long as the viral load remained undetectable. An increase was noted later in patients with immunologic and virological failures but also in patients with only virological failure.</p

Global Peak in Atmospheric Radiocarbon Provides a Potential Definition for the Onset of the Anthropocene Epoch in 1965

Anthropogenic activity is now recognised as having profoundly and permanently altered the Earth system, suggesting we have entered a human-dominated geological epoch, the ‘Anthropocene’. To formally define the onset of the Anthropocene, a synchronous global signature within geological-forming materials is required. Here we report a series of precisely-dated tree-ring records from Campbell Island (Southern Ocean) that capture peak atmospheric radiocarbon (14C) resulting from Northern Hemisphere-dominated thermonuclear bomb tests during the 1950s and 1960s. The only alien tree on the island, a Sitka spruce (Picea sitchensis), allows us to seasonally-resolve Southern Hemisphere atmospheric 14C, demonstrating the ‘bomb peak’ in this remote and pristine location occurred in the last-quarter of 1965 (October-December), coincident with the broader changes associated with the post-World War II ‘Great Acceleration’ in industrial capacity and consumption. Our findings provide a precisely-resolved potential Global Stratotype Section and Point (GSSP) or ‘golden spike’, marking the onset of the Anthropocene Epoch