Saprolegnia diclina IIIA and S. parasitica employ different infection strategies when colonizing eggs of Atlantic salmon, Salmo salar L.

Acknowledgements The work has been funded by the European Commission through the EU Marie Curie ITN project SAPRO (238550) (MMS, AW). We would also like to acknowledge support from the BBSRC and the University of Aberdeen (PvW) and Landcatch and AquaGen for providing salmon eggs. Elin Rolen's assistance with sequencing of the strains is highly appreciated.Peer reviewedPublisher PD

Effects of Patient-Directed Music Intervention on Anxiety and Sedative Exposure in Critically Ill Patients Receiving Mechanical Ventilatory Support: A Randomized Clinical Trial

Importance: Alternatives to sedative medications, such as music, may alleviate the anxiety associated with ventilatory support. Objective: To test whether listening to self-initiated patient-directed music (PDM) can reduce anxiety and sedative exposure during ventilatory support in critically ill patients. Design, Setting, and Patients: Randomized clinical trial that enrolled 373 patients from 12 intensive care units (ICUs) at 5 hospitals in the Minneapolis-St Paul, Minnesota, area receiving acute mechanical ventilatory support for respiratory failure between September 2006 and March 2011. Of the patients included in the study, 86% were white, 52% were female, and the mean (SD) age was 59 (14) years. The patients had a mean (SD) Acute Physiology, Age and Chronic Health Evaluation III score of 63 (21.6) and a mean (SD) of 5.7 (6.4) study days. Interventions: Self-initiated PDM (n = 126) with preferred selections tailored by a music therapist whenever desired while receiving ventilatory support, self-initiated use of noise-canceling headphones (NCH; n = 122), or usual care (n = 125). Main Outcomes and Measures: Daily assessments of anxiety (on 100-mm visual analog scale) and 2 aggregate measures of sedative exposure (intensity and frequency). Results: Patients in the PDM group listened to music for a mean (SD) of 79.8 (126) (median [range], 12 [0-796]) minutes/day. Patients in the NCH group wore the noise-abating headphones for a mean (SD) of 34.0 (89.6) (median [range], 0 [0-916]) minutes/day. The mixed-models analysis showed that at any time point, patients in the PDM group had an anxiety score that was 19.5 points lower (95% CI, −32.2 to −6.8) than patients in the usual care group (P = .003). By the fifth study day, anxiety was reduced by 36.5% in PDM patients. The treatment × time interaction showed that PDM significantly reduced both measures of sedative exposure. Compared with usual care, the PDM group had reduced sedation intensity by −0.18 (95% CI, −0.36 to −0.004) points/day (P = .05) and had reduced frequency by −0.21 (95% CI, −0.37 to −0.05) points/day (P = .01). The PDM group had reduced sedation frequency by −0.18 (95% CI, −0.36 to −0.004) points/day vs the NCH group (P = .04). By the fifth study day, the PDM patients received 2 fewer sedative doses (reduction of 38%) and had a reduction of 36% in sedation intensity. Conclusions and Relevance: Among ICU patients receiving acute ventilatory support for respiratory failure, PDM resulted in greater reduction in anxiety compared with usual care, but not compared with NCH. Concurrently, PDM resulted in greater reduction in sedation frequency compared with usual care or NCH, and greater reduction in sedation intensity compared with usual care, but not compared with NCH. Trial Registration: clinicaltrials.gov Identifier: NCT00440700 Critically ill mechanically ventilated patients receive intravenous sedative and analgesic medications to reduce anxiety and promote comfort and ventilator synchrony. These potent medications are often administered at high doses for prolonged periods and are associated with adverse effects such as bradycardia, hypotension, gut dysmotility, immobility, weakness, and delirium.1-3 Despite protocols and sedation assessment tools that guide clinicians, patients still experience significant levels of anxiety.4,5 Unrelieved anxiety and fear are not only unpleasant symptoms that clinicians want to palliate, but increased sympathetic nervous system activity can cause dyspnea and increased myocardial oxygen demand.6 Sustained anxiety and sympathetic nervous system activation can decrease the ability to concentrate, rest, or relax.6,7 Mechanically ventilated patients have little control over pharmacological interventions to relieve anxiety; dosing and frequency of sedative and analgesic medications are controlled by intensive care unit (ICU) clinicians. Interventions are needed that reduce anxiety, actively involve patients, and minimize the use of sedative medications. Nonpharmacological interventions such as relaxing music are effective in reducing anxiety while reducing medication administration.8,9 Music is a powerful distractor that can alter perceived levels of anxiety10 by occupying attention channels in the brain with meaningful, auditory stimuli11 rather than stressful environmental stimuli. Listening to preferred, relaxing music has reduced anxiety in mechanically ventilated patients in limited trials.12-15 It is not known if music can reduce anxiety throughout the course of ventilatory support, or reduce exposure to sedative medications. We evaluated if a patient-directed music (PDM) intervention could reduce anxiety and sedative exposure in ICU patients receiving mechanical ventilation

Mobile camera-space manipulation

The invention is a method of using computer vision to control systems consisting of a combination of holonomic and nonholonomic degrees of freedom such as a wheeled rover equipped with a robotic arm, a forklift, and earth-moving equipment such as a backhoe or a front-loader. Using vision sensors mounted on the mobile system and the manipulator, the system establishes a relationship between the internal joint configuration of the holonomic degrees of freedom of the manipulator and the appearance of features on the manipulator in the reference frames of the vision sensors. Then, the system, perhaps with the assistance of an operator, identifies the locations of the target object in the reference frames of the vision sensors. Using this target information, along with the relationship described above, the system determines a suitable trajectory for the nonholonomic degrees of freedom of the base to follow towards the target object. The system also determines a suitable pose or series of poses for the holonomic degrees of freedom of the manipulator. With additional visual samples, the system automatically updates the trajectory and final pose of the manipulator so as to allow for greater precision in the overall final position of the system

Analytical Validation of Variants to Aid in Genotype-Guided Therapy for Oncology

The Clinical Laboratory Improvement Amendments (CLIA) of 1988 requires that pharmacogenetic genotyping methods need to be established according to technical standards and laboratory practice guidelines before testing can be offered to patients. Testing methods for variants in ABCB1, CBR3, COMT, CYP3A7, C8ORF34, FCGR2A, FCGR3A, HAS3, NT5C2, NUDT15, SBF2, SEMA3C, SLC16A5, SLC28A3, SOD2, TLR4, and TPMT were validated in a CLIA-accredited laboratory. As no known reference materials were available, DNA samples that were from Coriell Cell Repositories (Camden, NJ) were used for the analytical validation studies. Pharmacogenetic testing methods developed here were shown to be accurate and 100% analytically sensitive and specific. Other CLIA-accredited laboratories interested in offering pharmacogenetic testing for these genetic variants, related to genotype-guided therapy for oncology, could use these publicly available samples as reference materials when developing and validating new genetic tests or refining current assays

Economic evaluation of a patient-directed music intervention for ICU patients receiving mechanical ventilatory support

Objectives: Music intervention has been shown to reduce anxiety and sedative exposure among mechanically ventilated patients. Whether music intervention reduces ICU costs is not known. The aim of this study was to examine ICU costs for patients receiving a patient-directed music intervention compared with patients who received usual ICU care. Design: A cost-effectiveness analysis from the hospital perspective was conducted to determine if patient-directed music intervention was cost-effective in improving patient-reported anxiety. Cost savings were also evaluated. One-way and probabilistic sensitivity analyses determined the influence of input variation on the cost-effectiveness. Setting: Midwestern ICUs. Patients: Adult ICU patients from a parent clinical trial receiving mechanical ventilatory support. Interventions: Patients receiving the experimental patient-directed music intervention received a MP3 player, noise-canceling headphones, and music tailored to individual preferences by a music therapist. Measurements and Main Results: The base case cost-effectiveness analysis estimated patient-directed music intervention reduced anxiety by 19 points on the Visual Analogue Scale-Anxiety with a reduction in cost of $2,322/patient compared with usual ICU care, resulting in patient-directed music dominance. The probabilistic cost-effectiveness analysis found that average patient-directed music intervention costs were$2,155 less than usual ICU care and projected that cost saving is achieved in 70% of 1,000 iterations. Based on break-even analyses, cost saving is achieved if the per-patient cost of patient-directed music intervention remains below $2,651, a value eight times the base case of$329. Conclusions: Patient-directed music intervention is cost-effective for reducing anxiety in mechanically ventilated ICU patients

Adherence and Tolerability of Alzheimer's Disease Medications: A Pragmatic Randomized Trial

BACKGROUND/OBJECTIVES: Post-marketing comparative trials describe medication use patterns in diverse, real-world populations. Our objective was to determine if differences in rates of adherence and tolerability exist among new users to acetylcholinesterase inhibitors (AChEI's). DESIGN: Pragmatic randomized, open label comparative trial of AChEI's currently available in the United States. SETTING: Four memory care practices within four healthcare systems in the greater Indianapolis area. PARTICIPANTS: Eligibility criteria included older adults with a diagnosis of possible or probable Alzheimer's disease (AD) who were initiating treatment with an AChEI. Participants were required to have a caregiver to complete assessments, access to a telephone, and be able to understand English. Exclusion criteria consisted of a prior severe adverse event from AChEIs. INTERVENTION: Participants were randomized to one of three AChEIs in a 1:1:1 ratio and followed for 18 weeks. MEASUREMENTS: Caregiver-reported adherence, defined as taking or not taking study medication, and caregiver-reported adverse events, defined as the presence of an adverse event. RESULTS: 196 participants were included with 74.0% female, 30.6% African Americans, and 72.9% who completed at least twelfth grade. Discontinuation rates after 18 weeks were 38.8% for donepezil, 53.0% for galantamine, and 58.7% for rivastigmine (P = .063) in the intent to treat analysis. Adverse events and cost explained 73.1% and 25.4% of discontinuation. No participants discontinued donepezil due to cost. Adverse events were reported by 81.2% of all participants; no between-group differences in total adverse events were statistically significant. CONCLUSIONS: This pragmatic comparative trial showed high rates of adverse events and cost-related non-adherence with AChEIs. Interventions improving adherence and persistence to AChEIs may improve AD management. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01362686 (https://clinicaltrials.gov/ct2/show/NCT01362686)

On the electromagnetic properties of active media

Several results concerning active media or metamaterials are proved and discussed. In particular, we consider the permittivity, permeability, wave vector, and refractive index, and discuss stability, refraction, gain, and fundamental limitations resulting from causality

Assessing the Contribution of Heme-Iron Acquisition to Staphylococcus aureus Pneumonia Using Computed Tomography

S. aureus acquires heme-iron using the iron regulated surface determinant (Isd) system and the heme transport system (Hts) with both systems showing critical importance in systemic models of infection. The contribution of heme-iron acquisition to staphylococcal pneumonia has not yet been elucidated. In addition, the use of computed tomography (CT) for the evaluation of staphylococcal pneumonia and its correlation to pathologic examination of infected lung tissue has not been performed to date. We have applied CT-based imaging to a murine model of staphylococcal pneumonia to determine the virulence contribution of heme-iron acquisition through the Hts and Isd systems.Mice were intranasally inoculated with approximately 1.0 x 10(8) colony forming units (CFU) of S. aureus. Lungs from mice infected with wild type S. aureus or strains deficient in isdB and isdH (DeltaisdBH) or htsA and isdE (DeltahtsADeltaisdE) were harvested at 24 hours. Histology, radiographic appearance by computed tomography (CT), percent mortality and bacterial burden were evaluated. Infection with S. aureus DeltaisdBH and DeltahtsADeltaisdE did not result in a statistically significant difference in mortality or bacterial burden as compared to controls. CT imaging of infected mice also did not reveal an appreciable difference between the various strains when compared to wild type, but did correlate with pathologic findings of pneumonia. However, a systemic model of infection using the DeltahtsADeltaisdE strain revealed a statistically significant decrease in bacterial burden in the lung, heart and kidneys.The development of staphylococcal pneumonia in this murine model is not dependent on hemoglobin binding or heme-iron uptake into S. aureus. However, this model does reveal that heme-iron acquisition contributes to the pathogenesis of systemic staphylococcal infections. In addition, CT imaging of murine lungs is an attractive adjunct to histologic analysis for the confirmation and staging of pneumonia