The majority of known Toxoplasma gondii isolates from Europe and North America belong to three clonal lines that differ dramatically in their virulence, depending on the host. To identify the ...responsible genes, we mapped virulence in F₁ progeny derived from crosses between type II and type III strains, which we introduced into mice. Five virulence (VIR) loci were thus identified, and for two of these, genetic complementation showed that a predicted protein kinase (ROP18 and ROP16, respectively) is the key molecule. Both are hypervariable rhoptry proteins that are secreted into the host cell upon invasion. These results suggest that secreted kinases unique to the Apicomplexa are crucial in the host-pathogen interaction.
A common feature of microarray experiments is the occurrence of missing gene expression data. These missing values occur for a variety of reasons, in particular, because of the filtering of poor ...quality spots and the removal of undefined values when a logarithmic transformation is applied to negative background-corrected intensities. The efficiency and power of an analysis performed can be substantially reduced by having an incomplete matrix of gene intensities. Additionally, most statistical methods require a complete intensity matrix. Furthermore, biases may be introduced into analyses through missing information on some genes. Thus methods for appropriately replacing (imputing) missing data and/or weighting poor quality spots are required.
We present a likelihood-based method for imputing missing data or weighting poor quality spots that requires a number of biological or technical replicates. This likelihood-based approach assumes that the data for a given spot arising from each channel of a two-dye (two-channel) cDNA microarray comparison experiment independently come from a three-component mixture distribution--the parameters of which are estimated through use of a constrained E-M algorithm. Posterior probabilities of belonging to each component of the mixture distributions are calculated and used to decide whether imputation is required. These posterior probabilities may also be used to construct quality weights that can down-weight poor quality spots in any analysis performed afterwards. The approach is illustrated using data obtained from an experiment to observe gene expression changes with 24 hr paclitaxel (Taxol) treatment on a human cervical cancer derived cell line (HeLa).
As the quality of microarray experiments affect downstream processes, it is important to have a reliable and automatic method of identifying poor quality spots and arrays. We propose a method of identifying poor quality spots, and suggest a method of repairing the arrays by either imputation or assigning quality weights to the spots. This repaired data set would be less biased and can be analysed using any of the appropriate statistical methods found in the microarray literature.
Abstract
Corals are under siege by both local and global threats, creating a worldwide reef crisis. Cryopreservation is an important intervention measure and a vital component of the modern coral ...conservation toolkit, but preservation techniques are currently limited to sensitive reproductive materials that can only be obtained a few nights per year during spawning. Here, we report the successful cryopreservation and revival of cm-scale coral fragments via mL-scale isochoric vitrification. We demonstrate coral viability at 24 h post-thaw using a calibrated oxygen-uptake respirometry technique, and further show that the method can be applied in a passive, electronics-free configuration. Finally, we detail a complete prototype coral cryopreservation pipeline, which provides a platform for essential next steps in modulating post-thaw stress and initiating long-term growth. These findings pave the way towards an approach that can be rapidly deployed around the world to secure the biological genetic diversity of our vanishing coral reefs.
Abstract Background Cardiac resynchronization therapy (CRT) has been shown to improve heart failure (HF) symptoms and survival. We hypothesized that a greater improvement in left-ventricular ejection ...fraction (LVEF) after CRT is associated with greater survival benefit. Methods and Results In 693 patients across 2 international centers, the improvement in LVEF after CRT was determined. Patients were grouped as non-/modest-, moderate-, or super-responders to CRT, defined as an absolute change in LVEF of ≤5%, 6–15%, and >15%, respectively. Changes in New York Heart Association (NYHA) functional class and left ventricular end-diastolic dimension (LVEDD) were assessed for each group. There were 395 non-/modest-, 186 moderate-, and 112 super-responders. Super-responders were more likely to be female and to have nonischemic cardiomyopathy, lower creatinine, and lower pulmonary artery systolic pressure than non-/modest- and moderate-responders. Super-responders were also more likely to have lower LVEF than non-/modest-responders. There was no difference in NYHA functional class, mitral regurgitation grade, or tricuspid regurgitation grade between groups. Improvement in NYHA functional class (−0.9 ± 0.9 vs −0.4 ± 0.8 P < .001 and −0.6 ± 0.8 P = .02) and LVEDD (−8.7 ± 9.9 mm vs −0.5 ± 5.0 and −2.4 ± 5.8 mm P < .001 for both) was greatest in super-responders. Kaplan-Meier survival analysis revealed that super-responders achieved better survival compared with non-/modest- ( P < .001) and moderate-responders ( P = .049). Conclusions Improvement in HF symptoms and survival after CRT is proportionate to the degree of improvement in LV systolic function. Super-response is more likely in women, those with nonischemic substrate, and those with lower pulmonary artery systolic pressure.
Introduction: The quality of an Emergency Medical Technician (EMT) or paramedic training program is likely one factor that contributes to a candidate's success on the National Registry Cognitive ...Examination. However, program pass rates and their associated geographic location have not previously been evaluated. Our objective was to evaluate the performance of EMT and paramedic programs in the United States, pass rates on the National Registry Cognitive Examinations, and relationship to geography.
Methods: We conducted a cross-sectional evaluation of EMT and paramedic programs' first and cumulative third attempt pass rates on the National Registry Cognitive Examination in 2015. Included were civilian EMT and paramedic programs with >5 graduates testing for certification. Descriptive statistics were calculated for program pass rates, total graduates testing, and pass rates by National Association of State EMS Officials (NASEMSO) regions.
Results: We included 1,939 EMT programs (6-1,892 graduates testing/program) and 602 paramedic programs (6-689 graduates testing/program). We excluded 262 (11.9%) EMT and 51 (7.8%) paramedic programs with ≤5 graduates testing annually due to unstable estimates of program pass rates. EMT programs in the highest quartile for total number of graduates testing outperformed the lowest quartile in both first attempt (65.7% vs. 61.9%, p < 0.001) and cumulative third attempt pass rates (79.1% vs 72.7%, p < 0.001). This difference was also seen for paramedic programs on first attempt (77.3% vs. 62.5%, p < 0.001) and cumulative third attempt (91.9% vs. 76.9%, p < 0.001). EMT program pass rates for first and cumulative third attempts also varied by NASEMSO region (first: 62-68%; third: 74-78%) with the Great Lakes and West regions outperforming the other regions. Paramedic program pass rates differed by NASEMSO regions as well (first: 65-83%; third: 81-95%) with highest pass rates in the West region.
Conclusions Program performance for both EMT and paramedic programs varies by total number of graduates testing and geographic location. Graduates from larger EMT and paramedic programs have higher first and cumulative third attempt pass rates compared to graduates from smaller programs. Additionally, there is variability in program pass rates across NASEMSO regions for both certification levels. Further evaluation is necessary to better understand the variability in program performance in the United States.
Mass critical care entails time-sensitive decisions and changes in the standard of care that it is possible to deliver. These circumstances increase provider uncertainty as well as patients' ...vulnerability and may, therefore, jeopardize disciplined, ethical decision-making. Planning for pandemics and disasters should incorporate ethics guidance to support providers who may otherwise make ad hoc patient care decisions that overstep ethical boundaries. This article provides consensus-developed suggestions about ethical challenges in caring for the critically ill or injured during pandemics or disasters. The suggestions in this article are important for all of those involved in any pandemic or disaster with multiple critically ill or injured patients, including front-line clinicians, hospital administrators, and public health or government officials.
We adapted the American College of Chest Physicians (CHEST) Guidelines Oversight Committee's methodology to develop suggestions. Twenty-four key questions were developed, and literature searches were conducted to identify evidence for suggestions. The detailed literature reviews produced 144 articles. Based on their expertise within this domain, panel members also supplemented the literature search with governmental publications, interdisciplinary workgroup consensus documents, and other information not retrieved through PubMed. The literature in this field is not suitable to support evidence-based recommendations. Therefore, the panel developed expert opinion-based suggestions using a modified Delphi process.
We report the suggestions that focus on five essential domains: triage and allocation, ethical concerns of patients and families, ethical responsibilities to providers, conduct of research, and international concerns.
Ethics issues permeate virtually all aspects of pandemic and disaster response. We have addressed some of the most pressing issues, focusing on five essential domains: triage and allocation, ethical concerns of patients and families, ethical responsibilities to providers, conduct of research, and international concerns. Our suggestions reflect the consensus of the Task Force. We recognize, however, that some suggestions, including those related to end-of-life care, may be controversial. We highlight the need for additional research and dialogue in articulating values to guide health-care decisions during disasters.
CDC, the Food and Drug Administration (FDA), state and local health departments, and public health and clinical partners are investigating a multistate outbreak of lung injury associated with the use ...of electronic cigarette (e-cigarette), or vaping, products. In late August, CDC released recommendations for health care providers regarding e-cigarette, or vaping, product use associated lung injury (EVALI) based on limited data from the first reported cases (1,2). This report summarizes national surveillance data describing clinical features of more recently reported cases and interim recommendations based on these data for U.S. health care providers caring for patients with suspected or known EVALI. It provides interim guidance for 1) initial clinical evaluation; 2) suggested criteria for hospital admission and treatment; 3) patient follow-up; 4) special considerations for groups at high risk; and 5) clinical and public health recommendations. Health care providers evaluating patients suspected to have EVALI should ask about the use of e-cigarette, or vaping, products in a nonjudgmental and thorough manner. Patients suspected to have EVALI should have a chest radiograph (CXR), and hospital admission is recommended for patients who have decreased blood oxygen (O
) saturation (<95%) on room air or who are in respiratory distress. Health care providers should consider empiric use of a combination of antibiotics, antivirals, or steroids based upon clinical context. Evidence-based tobacco product cessation strategies, including behavioral counseling, are recommended to help patients discontinue use of e-cigarette, or vaping, products. To reduce the risk of recurrence, patients who have been treated for EVALI should not use e-cigarette, or vaping, products. CDC recommends that persons should not use e-cigarette, or vaping, products that contain tetrahydrocannabinol (THC). At present, CDC recommends persons consider refraining from using e-cigarette, or vaping, products that contain nicotine. Irrespective of the ongoing investigation, e-cigarette, or vaping, products should never be used by youths, young adults, or women who are pregnant. Persons who do not currently use tobacco products should not start using e-cigarette, or vaping, products.
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