AEgIS at ELENA: outlook for physics with a pulsed cold antihydrogen beam.

The efficient production of cold antihydrogen atoms in particle traps at CERN's Antiproton Decelerator has opened up the possibility of performing direct measurements of the Earth's gravitational acceleration on purely antimatter bodies. The goal of the AEgIS collaboration is to measure the value of g for antimatter using a pulsed source of cold antihydrogen and a Moiré deflectometer/Talbot-Lau interferometer. The same antihydrogen beam is also very well suited to measuring precisely the ground-state hyperfine splitting of the anti-atom. The antihydrogen formation mechanism chosen by AEgIS is resonant charge exchange between cold antiprotons and Rydberg positronium. A series of technical developments regarding positrons and positronium (Ps formation in a dedicated room-temperature target, spectroscopy of the n=1-3 and n=3-15 transitions in Ps, Ps formation in a target at 10 K inside the 1 T magnetic field of the experiment) as well as antiprotons (high-efficiency trapping of [Formula: see text], radial compression to sub-millimetre radii of mixed [Formula: see text] plasmas in 1 T field, high-efficiency transfer of [Formula: see text] to the antihydrogen production trap using an in-flight launch and recapture procedure) were successfully implemented. Two further critical steps that are germane mainly to charge exchange formation of antihydrogen-cooling of antiprotons and formation of a beam of antihydrogen-are being addressed in parallel. The coming of ELENA will allow, in the very near future, the number of trappable antiprotons to be increased by more than a factor of 50. For the antihydrogen production scheme chosen by AEgIS, this will be reflected in a corresponding increase of produced antihydrogen atoms, leading to a significant reduction of measurement times and providing a path towards high-precision measurements.This article is part of the Theo Murphy meeting issue 'Antiproton physics in the ELENA era'.

Optimizing Scripted Dialogues for an e-Health Intervention for Suicidal Veterans with Major Depression.

Suicide is a health concern among Veterans with depression. We had previously reported on scripted dialogues adapted for an e-health system that engages at-risk veterans with schizophrenia. Here we report a further adaptation of the dialogues for Veterans with depression. Usability was assessed with nine outpatients with a history of major depression and suicidality. We noted that participants preferred greater specificity in the wording of questions. Topics that elicited an emotional response dealt with questions on suicide, social isolation and family relationships. Based on feedback, dialogues were revised for patients with depression. We also compared responses between those with depression and those with schizophrenia who were previously tested. The two groups shared similar themes. Also, individuals with a history of major depression had less trouble with vocabulary comprehension but were less willing to answer more questions daily.

Safety profile and protocol prevention of adverse reactions to uroangiographic contrast media in diagnostic imaging.

The purpose of the study is to examine the incidence of adverse reactions caused by non-ionic contrast media in selected patients after desensitization treatment and to evaluate the safety profile of organ iodine contrast media (i.c.m.) in a multistep prevention protocol. In a population of 2000 patients that had received a CT scan, 100 patients with moderate/high risk for adverse reactions against iodinated contrast agents followed a premedication protocol and all adverse reactions are reported and classified as mild, moderate or severe. 1.7 percent of the pre-treated patients reported a mild, immediate type reaction to iodine contrast; of these five patients with allergy 0.71 percent had received iomeprol, 0.35 percent received ioversol and 0.71 percent received iopromide. The incidence of adverse reactions was reported to be higher (4 out of 5 patients) among those that referred a history of hypersensitivity against iodinated i.c.m. Although intravenous contrast materials have greatly improved, especially in terms of their safety profile, they should not be administered if there isn't a clear or justified indication. In conclusion, even if we know that the majority of these reactions are idiosyncratic and unpredictable we propose, with the aim of improving our knowledge on this subject, a multicenter study, based on skin allergy tests (prick test, patch test, intradermal reaction) in selected patients that have had previous experiences of hypersensitivity against parenteral organ iodine contrast media.

Development of telehealth dialogues for monitoring suicidal patients with schizophrenia: consumer feedback.

Suicide is a health concern among individuals with schizophrenia. A telehealth system for monitoring suicidal patients with schizophrenia was developed using the Health Buddy©. The existing dialogues were improved using an expert panel; the new dialogues were tested in 10 consumers with schizophrenia and a history of suicidal behavior. Using qualitative editing, several themes emerged: (1) Certain topics elicited strong emotional responses; (2) There were concerns with confidentiality; (3) Some content was too vague and (4) There were problems with vocabulary and wording. The process yielded information for improving the intervention and demonstrated that the approach is feasible in this population.

An accurate model for the computation of the dose of protons in water.

PURPOSE: The accurate and fast calculation of the dose in proton radiation therapy is an essential ingredient for successful treatments. We propose a novel approach with a minimal number of parameters. METHODS: The approach is based on the exact calculation of the electromagnetic part of the interaction, namely the Molière theory of the multiple Coulomb scattering for the transversal 1D projection and the Bethe-Bloch formula for the longitudinal stopping power profile, including a gaussian energy straggling. To this e.m. contribution the nuclear proton-nucleus interaction is added with a simple two-parameter model. Then, the non gaussian lateral profile is used to calculate the radial dose distribution with a method that assumes the cylindrical symmetry of the distribution. RESULTS: The results, obtained with a fast C++ based computational code called MONET (MOdel of ioN dosE for Therapy), are in very good agreement with the FLUKA MC code, within a few percent in the worst case. CONCLUSIONS: This study provides a new tool for fast dose calculation or verification, possibly for clinical use.

On the lateral dose profile of 4He beams in water.

PURPOSE: We investigate the possibility to improve the accuracy of the lateral dose profile for 4He beams with a novel approach, by extending an already validated model for proton beams to heavier ions. METHODS: The full Molière theory for the Coulomb multiple scattering is applied to the case of 4He beams, with a complete separation of the electromagnetic and of the nuclear contributions in the calculation of the total dose. The latter is described with only three free parameters. RESULTS: The accuracy of the results compared with Monte Carlo predictions already validated with experimental data is comparable with other studies at low energy, but improves by a factor 2 at high energy. In addition the found solution is more stable with respect to (multi-) Gaussian and other parameterizations. This result makes this method of interest for applications to Treatment Planning Systems (TPS) in ion beam therapy. CONCLUSIONS: We propose a model, named MONETα (MOdel of ioN dosE for Therapy for α), for the calculation of the lateral dose of 4He beams in water that allows fast and accurate dose calculations by requiring a small data base of parameters as input.

On Molière and Fermi-Eyges scattering theories in hadrontherapy.

We consider the evaluation of lateral spread distributions of charged particle beams at therapeutic energies, due to an absorber in the form of a homogeneous slab or of a stack. We show that the Molière theory has the same degree of flexibility as the Fermi-Eyges, but is much more accurate and does not present particular computing difficulties with the energy loss formula we have employed. It is also shown that the non-Gaussian shape of the projected one dimensional (1D) distributions is not a complication for passing from the projected to the spatial two-dimensional (2D) distribution, if one assumes circular symmetry. All the calculations are compared with the results of the FLUKA code. The nuclear interaction is not considered here, because it is outside of the scope of this work.

A model for the accurate computation of the lateral scattering of protons in water.

A pencil beam model for the calculation of the lateral scattering in water of protons for any therapeutic energy and depth is presented. It is based on the full Molière theory, taking into account the energy loss and the effects of mixtures and compounds. Concerning the electromagnetic part, the model has no free parameters and is in very good agreement with the FLUKA Monte Carlo (MC) code. The effects of the nuclear interactions are parametrized with a two-parameter tail function, adjusted on MC data calculated with FLUKA. The model, after the convolution with the beam and the detector response, is in agreement with recent proton data in water from HIT. The model gives results with the same accuracy of the MC codes based on Molière theory, with a much shorter computing time.

Use of intensive care units for patients with low severity of illness.

OBJECTIVE: To determine variations among hospitals in use of intensive care units (ICUs) for patients with low severity of illness. DESIGN: Retrospective cohort study. SETTING: Twenty-eight hospitals with 44 ICUs in a large metropolitan region. PATIENTS: Consecutive eligible patients (N=104,487) admitted to medical, surgical, neurological, or mixed medical-surgical ICUs from March 1, 1991, to March 31, 1995. OUTCOME MEASURES: The predicted risk of in-hospital death for each patient was assessed using a validated method that is based on age, ICU admission source, diagnosis, severe comorbid conditions, and abnormalities in 17 physiologic variables. Admissions were classified as low severity if the patient's predicted risk of death was less than 1%. In a subset of 12,929 consecutive patients, use of 19 specific interventions typically delivered in ICUs was examined. RESULTS: Twenty thousand four hundred fifty-one admissions (19.6%) were categorized as low severity, including 23.6% of postoperative and 16.9% of nonoperative admissions. Alcohol and other drug overdoses accounted for 40.2% of nonoperative low-severity admissions; laminectomy and carotid endarterectomy accounted for 52.3% of postoperative low-severity admissions. Mortality among patients with low-severity illness was 0.3%, and only 28.6% received an ICU-specific intervention during the first ICU day. Although mean ICU length of stay was shorter (P<.001) in low-severity admissions (2.2 vs 4.7 days in nonoperative and 2.4 vs 4.2 days in postoperative admissions), low-severity admissions accounted for 11.1% of total ICU bed days. Rates of low-severity admissions varied (P<.001) across hospitals, ranging from 5% to 27% for nonoperative and 9% to 68% for postoperative admissions. CONCLUSIONS: A large proportion of patients admitted to the ICU have a low probability of death and do not receive ICU-specific interventions. Rates of low-severity admissions varied among hospitals. The development and implementation of protocols to target ICU care to patients most likely to benefit may decrease the number of low-severity ICU admissions and improve the cost-effectiveness of ICU care.

Oestrogen receptor in mammary gland cytosol of virgin, pregnant and lactating mice.

A macromolecular component binding 3H-labelled 17 beta-oestradiol in a specific manner and sedimenting in the 8-10-S region on sucrose gradient has been detected in the mammary gland cytosol of ovariectomized adult virgin mice. The dissociation constant of the macromolecule-oestradiol complex is 4.2 times 10(-10)M at 4 degrees C. The binding sites for 17beta-oestradiol of cytosol are 3.7 times 10(-14) mole/mg of protein. Incubation of cytosol with different enzymes suggests that the oestrogen-binding cytosol component is proteinaceous. The binding activity is destroyed by incubation at high temperatures and by some but not all SH-reagents tested. Competition studies show a specificity for oestrogens relative to other steroid hormones. The conclusion is that mammary gland cytosol of virgin mice contains oestradiol receptor. The receptor content does not increase in a specific manner during pregnancy and lactation but rather proportionally to total mammary gland protein.

Community-wide assessment of intensive care outcomes using a physiologically based prognostic measure: implications for critical care delivery from Cleveland Health Quality Choice.

STUDY OBJECTIVES: To examine the applicability of a previously developed intensive care prognostic measure to a community-based sample of hospitals, and assess variations in severity-adjusted mortality across a major metropolitan region. DESIGN: Retrospective cohort study. SETTING: Twenty-eight hospitals with 38 ICUs participating in a community-wide initiative to measure performance supported by the business community, hospitals, and physicians. PATIENTS: Included in the study were 116,340 consecutive eligible patients admitted to medical, surgical, neurologic, and mixed medical/surgical ICUs between March 1, 1991, and March 31, 1995. MAIN OUTCOME MEASURES: The risk of hospital mortality was assessed using a previous risk prediction equation that was developed in a national sample, and a reestimated logistic regression model fit to the current sample. The standardized mortality ratio (SMR) (actual/predicted mortality) was used to describe hospital performance. RESULTS: Although discrimination of the previous national risk equation in the current sample was high (receiver operating characteristic [ROC] curve area = 0.90), the equation systematically overestimated the risk of death and was not as well calibrated (Hosmer-Lemeshow statistic, 2407.6, 8 df, p < 0.001). The locally derived equation had similar discrimination (ROC curve area = 0.91), but had improved calibration across all ranges of severity (Hosmer-Lemeshow statistic = 13.5, 8 df, p = 0.10). Hospital SMRs ranged from 0.85 to 1.21, and four hospitals had SMRs that were higher or lower (p < 0.01) than 1.0. Variation in SMRs tended to be greatest during the first year of data collection. SMRs also tended to decline over the 4 years (1.06, 1.02, 0.98, and 0.94 in years 1 to 4, respectively), as did mean hospital length of stay (13.0, 12.4, 11.6, and 11.1 days in years 1 to 4; p < 0.001). However, excluding the increasing (p < 0.001) number of patients discharged to skilled nursing facilities attenuated much of the decline in standardized mortality over time. CONCLUSIONS: A previously validated physiologically based prognostic measure successfully stratified patients in a large community-based sample by their risk of death. However, such methods may require recalibration when applied to new samples and to reflect changes in practice over time. Moreover, although significant variations in hospital standardized mortality were observed, changing hospital discharge practices suggest that in-hospital mortality may no longer be an adequate measure of ICU performance. Community-wide efforts with broad-based support from business, hospitals, and physicians can be sustained over time to assess outcomes associated with ICU care. Such efforts may provide important information about variations in patient outcomes and changes in practice patterns over time. Future efforts should assess the impact of such community-wide initiatives on health-care purchasing and institutional quality improvement programs.

Sex steroid hormones act as growth factors.

We observed that sex steroid hormones, like growth factors, stimulate the Src/Ras/erk pathway of cell lines derived from human mammary or prostate cancers. In addition, hormone-dependent pathway activation can be induced in Cos cells, upon transfection of classic steroid receptors. Cross-talks between sex steroid receptors regulate their association with Src and consequent pathway activation. Oestradiol treatment of MCF-7 cells triggers simultaneous association of ER with Src and p85, the regulatory subunit of phosphatidylinositol-3-kinase (PI3-kinase) and activation of Src- and PI3-K-dependent pathways. Activation of the latter pathway triggers cyclin D1 transcription, that is unaffected by Mek-1 activation. This suggests that simultaneous activation of different signalling effectors is required to target different cell cycle components. Thus, a novel reciprocal cross-talk between the two pathways appears to be mediated by the ER. In all tested cells, activation of the signalling pathways has a proliferative role. Transcriptionally inactive ER expressed in NIH 3T3 cells responds to hormone causing Src/Ras/Erk pathway activation and DNA synthesis. This suggests that in these cells genomic activity is required for later events of cell growth.

Consensus conferences in critical care medicine. Methodologies and impact.

Consensus conferences for the purposes of producing practice guidelines are occurring with increasing frequency both nationally and internationally. The international collaboration of national sciences in these efforts could have a dramatic impact on international standards of care. Too little emphasis is given to conference evaluations in terms of validity of methods, quality of recommendations, and influence on clinical practice and patient outcome. This article provides an overview of consensus methods used to produce guidelines in critical care. It also discusses the strengths and weaknesses of these methods, and how these may influence consensus guidelines. Finally, a brief overview of theoretically sound methods that can serve as benchmarks to evaluate current methods, and the bases for the development of improved methods is provided.

Benchmarking the perioperative process. I. Patient routing systems: a method for continual improvement of patient flow and resource utilization.

The article presents an overview of the design and application of a real-time patient routing system, based on barcode and local area network technology, that was designed to track the progress of patients during the perioperative process. We present data on all patients undergoing ambulatory surgery. Patients' progress during their surgical stay was recorded at 17 strategic events using this real-time patient tracking technology. These times were used to identify inefficiencies in the perioperative process by identifying bottlenecks and areas of high variation. We found that both raw and actual operating room (OR) utilization efficiency was less than 50%. Points of high variation in a patient's progress occurred during the time from admit to the hospital until the patient was ready for the OR; the time from when a patient was ready for the OR until they were called for; and the time a patient spends in the OR preoperative holding room. Causes for variation were identified and traced back to individual procedures, activities, and work processes. Multidisciplinary improvement teams were created to improve the pinpointed problem areas. The real-time patient routing system is a process that has proven to be highly valuable to all participants in the surgical process in bringing about rational, data driven efficiencies in perioperative services. This process has the potential to facilitate multidisciplinary cooperation in efforts to contain and reduce costs of perioperative services.

An ethanol-based fixation method for anatomical and micro-morphological characterization of leaves of various tree species.

The use of formalin constitutes serious health hazards for laboratory workers. We investigated the suitability and performance of the ethanol-based fixative, FineFIX, as a substitute for formalin for anatomical and cellular structure investigations of leaves by light microscopy and for leaf surface and ultrastructural analysis by scanning electron microscopy (SEM). We compared the anatomical features of leaf materials prepared using conventional formalin fixation with the FineFIX. Leaves were collected from ornamental tree species commonly used in urban areas. FineFIX was also compared with glutaraldehyde fixation and air drying normally used for scanning electron microscopy to develop a new method for evaluating leaf morphology and microstructure in three ornamental tree species. The cytological features of the samples processed for histological analysis were well preserved by both fixatives as demonstrated by the absence of nuclear swelling or shrinkage, cell wall detachment or tissue flaking, and good presentation of cytoplasmic vacuolization. In addition, good preservation of surface details and the absence of shrinkage artefacts confirmed the efficacy of FineFIX fixation for SEM analysis. Cuticular wax was preserved only in air dried samples. Samples treated with chemical substances during the fixation and dehydration phases showed various alterations of the wax structures. In some air dried samples a loss of turgidity of the cells was observed that caused general wrinkling of the epidermal surfaces. Commercial FineFIX is an adequate substitute for formalin in histology and it can be applied successfully also for SEM investigation, while reducing the health risks of glutaraldehyde or other toxic fixatives. To investigate the potential for plants to absorb and capture particulates in air, which requires preservation of the natural morphology of trichomes and epicuticular waxes, a combination of FineFIX fixation and air drying is recommended.