Genome-wide identification of lineage and locus specific variation associated with pneumococcal carriage duration.

Streptococcus pneumoniae is a leading cause of invasive disease in infants, especially in low-income settings. Asymptomatic carriage in the nasopharynx is a prerequisite for disease, but variability in its duration is currently only understood at the serotype level. Here we developed a model to calculate the duration of carriage episodes from longitudinal swab data, and combined these results with whole genome sequence data. We estimated that pneumococcal genomic variation accounted for 63% of the phenotype variation, whereas the host traits considered here (age and previous carriage) accounted for less than 5%. We further partitioned this heritability into both lineage and locus effects, and quantified the amount attributable to the largest sources of variation in carriage duration: serotype (17%), drug-resistance (9%) and other significant locus effects (7%). A pan-genome-wide association study identified prophage sequences as being associated with decreased carriage duration independent of serotype, potentially by disruption of the competence mechanism. These findings support theoretical models of pneumococcal competition and antibiotic resistance

Entangled Pair Resource Allocation under Uncertain Fidelity Requirements

In quantum networks, effective entanglement routing facilitates remote entanglement communication between quantum source and quantum destination nodes. Unlike routing in classical networks, entanglement routing in quantum networks must consider the quality of entanglement qubits (i.e., entanglement fidelity), presenting a challenge in ensuring entanglement fidelity over extended distances. To address this issue, we propose a resource allocation model for entangled pairs and an entanglement routing model with a fidelity guarantee. This approach jointly optimizes entangled resources (i.e., entangled pairs) and entanglement routing to support applications in quantum networks. Our proposed model is formulated using two-stage stochastic programming, taking into account the uncertainty of quantum application requirements. Aiming to minimize the total cost, our model ensures efficient utilization of entangled pairs and energy conservation for quantum repeaters under uncertain fidelity requirements. Experimental results demonstrate that our proposed model can reduce the total cost by at least 20\% compared to the baseline model.Comment: 6 pages and 6 figure

Dynamics of cadmium acclimation in Daphnia pulex:linking fitness costs, cross-tolerance, and hyper-induction of metallothionein

Acclimation increases tolerance to stress in individuals but is assumed to contribute fitness costs when the stressor is absent, though data supporting this widely held claim are sparse. Therefore, using clonal (i.e., genetically identical) cultures of Daphnia pulex, we isolated the contributions of acclimation to the regulation of the metal response gene, metallothionein 1 (MT1), and defined the reproductive benefits and costs of cadmium (Cd)-acclimation. Daphnia pulex were exposed for 50 parthenogenetic generations to environmentally realistic levels (1 μg Cd/L), and tolerance to Cd and other metals assessed during this period via standard toxicity tests. These tests revealed (1) increased tolerance to Cd compared to genetically identical nonacclimated cultures, (2) fitness costs in Cd-acclimated Daphnia when Cd was removed, and (3) cross-tolerance of Cd-acclimated Daphnia to zinc and silver, but not arsenic, thereby defining a functional role for metallothionein. Indeed, Cd-acclimated clones had significantly higher expression of MT1 mRNA than nonacclimated clones, when Cd exposed. Both the enhanced induction of MT1 and tolerant phenotype were rapidly lost when Cd was removed (1–2 generations), which is further evidence of acclimation costs. These findings provide evidence for the widely held view that acclimation is costly and are important for investigating evolutionary principles of genetic assimilation and the survival mechanisms of natural populations that face changing environments

The Changing Role of Ancillary Health Care Service Providers: An Evaluation of Health Diagnostic Laboratory, Inc.

In an effort to reduce cost and improve quality, health care payers have enacted a number of incentives to motivate providers to focus their efforts on achieving better clinical outcomes and reducing the prevalence and progression of disease. In response to these incentives, providers are entering into new arrangements such as accountable care organizations and patient-centered medical homes to redesign delivery processes and achieve quality and cost objectives. This article reports the results of a study designed to evaluate the impact on cost and quality of care resulting from services provided by Health Diagnostic Laboratory, Inc., a clinical laboratory with a comprehensive care model. The results show that patients who utilized these laboratory services experienced lower total cost of care (23% reduction, P \u3c 0.01) and improved lipid profiles during the follow-up period. Total cost reductions were related to cost reductions found in both inpatient and ambulatory care. These findings suggest that accountable care organizations, patient-centered medical homes, and other groups entering shared savings initiatives should consider the potential role ancillary service providers with comprehensive care models can play in the delivery of integrated care. (Population Health Management 2014; 17: 121-126

Methodological problems in dementia research in primary care: a case study of a randomized controlled trial

The emerging UK national research network in neurodegenerative diseases and dementias aims to promote large-scale community-based studies of therapeutic interventions, based in primary care. However, trials in primary care settings can be problematic, a common difficulty being the recruitment of a large enough sample. The article discusses recruitment issues in a multi-centre randomized controlled trial of differing educational approaches to improving dementia care in general practice. Sample size calculations based on community studies of prevalence may be misleading in intervention trials which may recruit practices with atypical demography. Recruitment rates for practitioners in this study were lower than expected. Professionals excluded themselves from the study mainly due to pressures of time and staff shortages, and we detected both ambivalent attitudes to primary care research and a perception that research into dementia care was not a high priority. Evaluation of the quality of care may be perceived as criticism of clinical practice, at a time when general practice is undergoing major administrative and contractual changes. Variations in Research Ethics Committee conditions for approval led to different methods of recruitment of patients and carers into the study, a factor which may have contributed to disparate levels of recruitment across study sites. Patient and carer levels of recruitment were lower than expected and were affected partly by carers' time pressures and other family commitments, but largely by problems in identifying patients and carers in the practices. The development of research potential in primary care is at an early stage and studies reliant on patient recruitment in general practice must allow for multiple obstacles to enrollment. This is particularly relevant for studies of dementia care, where the prevalence of dementia in a demographically average population is low and the incidence very low, compared with other disabilities. Professionals may give dementia low priority in allocating practice time for research projects, and strategies to address this problem are needed

Causes and Consequences of Diachronous V-Shaped Ridges in the North Atlantic Ocean

In the North Atlantic Ocean, the geometry of diachronous V‐shaped features that straddle the Reykjanes Ridge is often attributed to thermal pulses which advect away from the center of the Iceland plume. Recently, two alternative hypotheses have been proposed: rift propagation and buoyant mantle upwelling. Here we evaluate these different proposals using basin‐wide geophysical and geochemical observations. The centerpiece of our analysis is a pair of seismic reflection profiles oriented parallel to flow lines that span the North Atlantic Ocean. V‐shaped ridges and troughs are mapped on both Neogene and Paleogene oceanic crust, enabling a detailed chronology of activity to be established for the last 50 million years. Estimates of the cumulative horizontal displacement across normal faults help to discriminate between brittle and magmatic modes of plate separation, suggesting that crustal architecture is sensitive to the changing planform of the plume. Water‐loaded residual depth measurements are used to estimate crustal thickness and to infer mantle potential temperature which varies by ±25°C on timescales of 3–8 Ma. This variation is consistent with the range of temperatures inferred from geochemical modeling of dredged basaltic rocks along the ridge axis itself, from changes in Neogene deep‐water circulation, and from the regional record of episodic Cenozoic magmatism. We conclude that radial propagation of transient thermal anomalies within an asthenospheric channel that is 150 ± 50 km thick best accounts for the available geophysical and geochemical observations