The BSAC guidelines on treatment of infectious endocarditis (IE) were last published in 2004. The guidelines presented here have been updated and extended to reflect developments in diagnostics, new ...trial data and the availability of new antibiotics. The aim of these guidelines, which cover both native valve and prosthetic valve endocarditis, is to standardize the initial investigation and treatment of IE. An extensive review of the literature using a number of different search criteria has been carried out and cited publications used to support any changes we have made to the existing guidelines. Publications referring to in vitro or animal models have only been cited if appropriate clinical data are not available. Randomized, controlled trials suitable for the development of evidenced-based guidelines in this area are still lacking and therefore a consensus approach has again been adopted for most recommendations; however, we have attempted to grade the evidence, where possible. The guidelines have also been extended by the inclusion of sections on clinical diagnosis, echocardiography and surgery.
These evidence-based guidelines are an updated version of those published in 2006. They have been produced after a literature review of the treatment and prophylaxis of methicillin-resistant ...Staphylococcus aureus (MRSA). The guidelines aim to complement those recently published for the antibiotic treatment of common and emerging community-onset MRSA infections in the UK. The guidelines have reviewed and updated, where appropriate, previous recommendations, taking into account any changes in the UK epidemiology of MRSA, ongoing national surveillance data and the value of new antistaphylococcal agents licensed for use in UK practice. Emerging therapies that have not been licensed for UK use are not reviewed, but their future potential role has been mentioned where deemed appropriate. Recommendations are given for the treatment of common infections caused by MRSA, elimination of MRSA from carriage sites and prophylaxis of surgical site infection.
Executive Summary
Return of samples from the surface of Mars has been a goal of the international Mars science community for many years. Affirmation by NASA and ESA of the importance of Mars ...exploration led the agencies to establish the international MSR Objectives and Samples Team (iMOST). The purpose of the team is to re‐evaluate and update the sample‐related science and engineering objectives of a Mars Sample Return (MSR) campaign. The iMOST team has also undertaken to define the measurements and the types of samples that can best address the objectives.
Seven objectives have been defined for MSR, traceable through two decades of previously published international priorities. The first two objectives are further divided into sub‐objectives. Within the main part of the report, the importance to science and/or engineering of each objective is described, critical measurements that would address the objectives are specified, and the kinds of samples that would be most likely to carry key information are identified. These seven objectives provide a framework for demonstrating how the first set of returned Martian samples would impact future Martian science and exploration. They also have implications for how analogous investigations might be conducted for samples returned by future missions from other solar system bodies, especially those that may harbor biologically relevant or sensitive material, such as Ocean Worlds (Europa, Enceladus, Titan) and others.
Summary of Objectives and Sub‐Objectives for MSR Identified by iMOST
Objective 1
Interpret the primary geologic processes and history that formed the Martian geologic record, with an emphasis on the role of water.
Intent
To investigate the geologic environment(s) represented at the Mars 2020 landing site, provide definitive geologic context for collected samples, and detail any characteristics that might relate to past biologic processesThis objective is divided into five sub‐objectives that would apply at different landing sites.
1.1 Characterize the essential stratigraphic, sedimentologic, and facies variations of a sequence of Martian sedimentary rocks.
Intent
To understand the preserved Martian sedimentary record.
Samples
A suite of sedimentary rocks that span the range of variation.
Importance
Basic inputs into the history of water, climate change, and the possibility of life
1.2 Understand an ancient Martian hydrothermal system through study of its mineralization products and morphological expression.
Intent
To evaluate at least one potentially life‐bearing “habitable” environment
Samples
A suite of rocks formed and/or altered by hydrothermal fluids.
Importance
Identification of a potentially habitable geochemical environment with high preservation potential.
1.3 Understand the rocks and minerals representative of a deep subsurface groundwater environment.
Intent
To evaluate definitively the role of water in the subsurface.
Samples
Suites of rocks/veins representing water/rock interaction in the subsurface.
Importance
May constitute the longest‐lived habitable environments and a key to the hydrologic cycle.
1.4 Understand water/rock/atmosphere interactions at the Martian surface and how they have changed with time.
Intent
To constrain time‐variable factors necessary to preserve records of microbial life.
Samples
Regolith, paleosols, and evaporites.
Importance
Subaerial near‐surface processes could support and preserve microbial life.
1.5 Determine the petrogenesis of Martian igneous rocks in time and space.
Intent
To provide definitive characterization of igneous rocks on Mars.
Samples
Diverse suites of ancient igneous rocks.
Importance
Thermochemical record of the planet and nature of the interior.
Objective 2
Assess and interpret the potential biological history of Mars, including assaying returned samples for the evidence of life.
Intent
To investigate the nature and extent of Martian habitability, the conditions and processes that supported or challenged life, how different environments might have influenced the preservation of biosignatures and created nonbiological “mimics,” and to look for biosignatures of past or present life.This objective has three sub‐objectives:
2.1 Assess and characterize carbon, including possible organic and pre‐biotic chemistry.
Samples
All samples collected as part of Objective 1.
Importance
Any biologic molecular scaffolding on Mars would likely be carbon‐based.
2.2 Assay for the presence of biosignatures of past life at sites that hosted habitable environments and could have preserved any biosignatures.
Samples
All samples collected as part of Objective 1.
Importance
Provides the means of discovering ancient life.
2.3 Assess the possibility that any life forms detected are alive, or were recently alive.
Samples
All samples collected as part of Objective 1.
Importance
Planetary protection, and arguably the most important scientific discovery possible.
Objective 3
Quantitatively determine the evolutionary timeline of Mars.
Intent
To provide a radioisotope‐based time scale for major events, including magmatic, tectonic, fluvial, and impact events, and the formation of major sedimentary deposits and geomorphological features.
Samples
Ancient igneous rocks that bound critical stratigraphic intervals or correlate with crater‐dated surfaces.
Importance
Quantification of Martian geologic history.
Objective 4
Constrain the inventory of Martian volatiles as a function of geologic time and determine the ways in which these volatiles have interacted with Mars as a geologic system.
Intent
To recognize and quantify the major roles that volatiles (in the atmosphere and in the hydrosphere) play in Martian geologic and possibly biologic evolution.
Samples
Current atmospheric gas, ancient atmospheric gas trapped in older rocks, and minerals that equilibrated with the ancient atmosphere.
Importance
Key to understanding climate and environmental evolution.
Objective 5
Reconstruct the processes that have affected the origin and modification of the interior, including the crust, mantle, core and the evolution of the Martian dynamo.
Intent
To quantify processes that have shaped the planet's crust and underlying structure, including planetary differentiation, core segregation and state of the magnetic dynamo, and cratering.
Samples
Igneous, potentially magnetized rocks (both igneous and sedimentary) and impact‐generated samples.
Importance
Elucidate fundamental processes for comparative planetology.
Objective 6
Understand and quantify the potential Martian environmental hazards to future human exploration and the terrestrial biosphere.
Intent
To define and mitigate an array of health risks related to the Martian environment associated with the potential future human exploration of Mars.
Samples
Fine‐grained dust and regolith samples.
Importance
Key input to planetary protection planning and astronaut health.
Objective 7
Evaluate the type and distribution of in‐situ resources to support potential future Mars exploration.
Intent
To quantify the potential for obtaining Martian resources, including use of Martian materials as a source of water for human consumption, fuel production, building fabrication, and agriculture.
Samples
Regolith.
Importance
Production of simulants that will facilitate long‐term human presence on Mars.
Summary of iMOST Findings
Several specific findings were identified during the iMOST study. While they are not explicit recommendations, we suggest that they should serve as guidelines for future decision making regarding planning of potential future MSR missions.
The samples to be collected by the Mars 2020 (M‐2020) rover will be of sufficient size and quality to address and solve a wide variety of scientific questions.
Samples, by definition, are a statistical representation of a larger entity. Our ability to interpret the source geologic units and processes by studying sample sub sets is highly dependent on the quality of the sample context. In the case of the M‐2020 samples, the context is expected to be excellent, and at multiple scales. (A) Regional and planetary context will be established by the on‐going work of the multi‐agency fleet of Mars orbiters. (B) Local context will be established at field area‐ to outcrop‐ to hand sample‐ to hand lens scale using the instruments carried by M‐2020.
A significant fraction of the value of the MSR sample collection would come from its organization into sample suites, which are small groupings of samples designed to represent key aspects of geologic or geochemical variation.
If the Mars 2020 rover acquires a scientifically well‐chosen set of samples, with sufficient geological diversity, and if those samples were returned to Earth, then major progress can be expected on all seven of the objectives proposed in this study, regardless of the final choice of landing site. The specifics of which parts of Objective 1 could be achieved would be different at each of the final three candidate landing sites, but some combination of critically important progress could be made at any of them.
An aspect of the search for evidence of life is that we do not know in advance how evidence for Martian life would be preserved in the geologic record. In order for the returned samples to be most useful for both understanding geologic processes (Objective 1) and the search for life (Objective 2), the sample collection should contain BOTH typical and unusual samples from the rock units explored. This consideration should be incorporated into sample selection and the design of the suites.
The retrieval missions of a MSR campaign should (1) minimize stray magnetic fields to which the samples would be exposed and carry a magnetic witness plate to record exposure, (2) collect and return atmospheric gas sample(s), and (3) collect additional dust and/or regolith sample mass if possible.
Cyclic arginyl-glycyl-aspartic acid peptide (cRGD) peptides show a high affinity towards αVβ3 integrin, a receptor overexpressed in many cancers. We aimed to combine the versatility of ultrasmall ...gold nanoparticles (usGNP) with the target selectivity of cRGD peptide for the directed delivery of a cytotoxic payload in a novel design. usGNPs were synthesized with a modified Brust-Schiffrin method and functionalized via amide coupling and ligand exchange and their uptake, intracellular trafficking, and toxicity were characterized. Our cRGD functionalized usGNPs demonstrated increased cellular uptake by αVβ3 integrin expressing cells, are internalized via clathrin-dependent endocytosis, accumulated in the lysosomes, and when loaded with mertansine led to increased cytotoxicity. Targeting via cRGD functionalization provides a mechanism to improve the efficacy, tolerability, and retention of therapeutic GNPs.
Aims: To evaluate performance of frequency doubling technology (FDT) perimetry using the Humphrey Matrix 24-2 thresholding program in a hospital eye service (HES) glaucoma clinic. Methods: A random ...sample of individuals referred consecutively to the HES for suspected glaucoma were examined with 24-2 threshold FDT in addition to routine clinical tests. The discriminatory power of FDT and standard automated perimetry (SAP) were assessed using glaucomatous optic nerve head appearance as the reference gold standard. Results: 48 of 62 eligible referred individuals were recruited. Glaucoma prevalence was 31%. Median test duration per eye was 5 minutes 16 seconds for FDT and 5 minutes 9 seconds for SAP. There was no significant difference (p = 0.184) between proportions of individuals with reliable test results (FDT 75%, SAP 63%). Using a clinically appropriate binary criterion for abnormal visual field, sensitivity and specificity levels were 100% and 26% respectively for FDT and 80% and 52% for SAP. Both tests had higher negative than positive predictive values with marginal differences between tests. Criterion free receiver operator characteristic analysis revealed minimal discriminatory power differences. Conclusions: In a HES glaucoma clinic in which new referrals are evaluated, threshold 24-2 FDT testing with the Humphrey Matrix has performance characteristics similar to SAP. These findings suggest threshold testing using the FDT Matrix and SAP is comparable when the 24-2 test pattern is used.
Aim:To evaluate the performance of the frequency doubling technology (FDT) 24-2-5 screening test by comparison with the established N-30-5 FDT screening test for detection of glaucoma.Method:A ...prospective random sample of individuals referred for possible glaucoma were tested with FDT screening tests 24-2-5 and N-30-5 using the Humphrey Matrix perimeter in addition to standard clinical examination relevant to glaucoma detection. Discriminatory power, reliability and test time of these tests were assessed and compared. The case definition for glaucoma was made by patient according to the established clinical diagnosis.Results:Of 63 referred eligible individuals, 53 (84%) were recruited. Sensitivity and specificity for the N-30-5 screening test was 78 and 85% respectively, compared with 83% and 75% for the 24-2-5 with areas under a receiver operator characteristic curve being 0.87 and 0.92. Differences between these indices were not statistically significant. For a specificity of 95%, sensitivity values were 76% and 56% for the 24-2-5 and N-30-5 respectively. Mean (standard deviation) test duration for the FDT 24-2-5 and N-30-5 screening tests were 111 (13) and 39 (10) seconds respectively (p<0.001). A total of 19 subjects (36%) produced unreliable test results in one or both eyes when tested with the 24-2-5 screening test compared with 5 subjects (9%) with the N-30-5 (p<0.0005).Conclusion:Minimal discriminatory power differences existed between the two screening tests evaluated, with both screening tests exhibiting high discriminatory power for detection of individuals with glaucoma. More individuals produced unreliable results on the 24-2-5 screening, which also took longer to perform.
Background Clinical depression and postdialysis fatigue are important concerns for patients with kidney failure and can have a negative impact on quality of life and survival. Study Design The ...FREEDOM (Following Rehabilitation, Economics and Everyday-Dialysis Outcome Measurements) Study is an ongoing prospective cohort study investigating the clinical and economic benefits of daily (6 times per week) hemodialysis (HD). In this interim report, as part of an a priori planned analysis, we examine the long-term impact of daily HD on depressive symptoms, measured using the Beck Depression Inventory (BDI) survey, and postdialysis recovery time, measured using a previously validated questionnaire. Setting & Participants Adult patients initiating daily HD with a planned 12-month follow-up. Outcomes & Measurements The BDI survey and postdialysis recovery time question were administered at baseline, and changes were assessed at months 4 and 12. Results 239 participants were enrolled (intention-to-treat cohort) and 128 completed the study (per-protocol cohort). Mean age was 52 years, 64% were men, 55% had an arteriovenous fistula, and 90% transitioned from in-center HD therapy. In the per-protocol cohort, there was a significant decrease in mean BDI score over 12 months (11.2 95% CI, 9.6-12.9 vs 7.8 95% CI, 6.5-9.1; P < 0.001). For robustness, the intention-to-treat analysis was performed, yielding similar results. The percentage of patients with depressive symptoms (BDI score >10) significantly decreased during 12 months (41% vs 27%; P = 0.03). Similarly, in the per-protocol cohort, there was a significant decrease in postdialysis recovery time over 12 months (476 95% CI, 359-594 vs 63 minutes 95% CI, 32-95; P < 0.001). The intention-to-treat analysis yielded similar results. The percentage of patients experiencing prolonged postdialysis recovery time (≥60 minutes) also significantly decreased (81% vs 35%; P = 0.001). Limitations Observational study with lack of control arm. Conclusions Daily HD is associated with long-term improvement in depressive symptoms and postdialysis recovery time.
AIM To examine the outcome of care for patients with glaucoma followed up by the hospital eye service compared with those followed up by community optometrists. METHODS A randomised study with ...patients allocated to follow up by the hospital eye service or community optometrists was carried out in the former county of Avon in south west England. 403 patients with established or suspected primary open angle glaucoma attending Bristol Eye Hospital and meeting defined inclusion and exclusion criteria were studied. The mean number of missed points on visual field testing in the better eye (using a “better/worse” eye analysis) in each group were measured. The visual field was measured using the Henson semiautomated central field analyser (CFA 3000). Measurements were made by the research team on all patients at baseline before randomisation and again 2 years after randomisation. The mean number of missed points on visual field testing in the worse eye, mean intraocular pressure (mm Hg), and cup disc ratio using a “better/worse” eye analysis in each group at 2 years were also measured. Measurements were made by the research team on all patients at baseline before randomisation and again 2 years after randomisation. An analysis of covariance comparing method of follow up taking into account baseline measurements of outcome variables was carried out. Additional control was considered for age, sex, diagnostic group (glaucoma suspect/established primary open angle glaucoma), and treatment (any/none). RESULTS From examination of patient notes, 2780 patients with established or suspected glaucoma were identified. Of these, 752 (27.1%) fulfilled the entry criteria. For hospital and community follow up group respectively, mean number of missed points on visual field testing at 2 year follow up for better eye was 7.9 points and 6.8 points; for the worse eye 20.2 points and 18.4 points. Similarly, intraocular pressure was 19.3 mm Hg and 19.3 mm Hg (better eye), and 19.1 mm Hg and 19.0 mm Hg (worse eye); cup disc ratio at 2 year follow up was 0.72 and 0.72 (better eye), and 0.74 and 0.74 for hospital and community follow up group respectively. No significant differences in any of the key visual variables were found between the two groups before or after adjusting for baseline values and age, sex, treatment, and type of glaucoma. CONCLUSIONS It is feasible to set and run shared care schemes for a proportion of patients with suspected and established glaucoma using community optometrists. After 2 years (a relatively short time in the life of a patient with glaucoma), there were no marked or statistically significant differences in outcome between patients followed up in the hospital eye service or by community optometrists. Decisions to implement such schemes need to be based on careful consideration of the costs of such schemes and local circumstances, including geographical access and the current organisation of glaucoma care within the hospital eye service.
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