Serum IL-5 and IL-13 consistently serve as the best predictors for the blood eosinophilia phenotype in adult asthmatics.

BACKGROUND: Molecular biomarkers that identify the phenotype of blood eosinophilia were evaluated in adult asthmatics, and their relationship with clinically significant asthma outcomes was assessed. Patients were clustered based on their molecular fingerprint. METHODS: At inclusion, 64 patients were evaluated for phenotypic traits, sputum and blood eosinophilia, exhaled NO, serum cytokines and chemokines, total serum IgE, lung function (LF), and airway hyper-responsiveness (AHR). Within-patient changes were evaluated in 44 patients 6 weeks later. RESULTS: Lung function, asthma control, and monocyte chemotactic protein-1 (MCP-1) were identified as the most important distinguisher and blood eosinophilia as second most important identifier in principal component analysis. A robust relationship was observed between blood eosinophilia and IL-5, IL-13, and eosinophil-derived neurotoxin (EDN), which stayed consistent after 6 weeks. Serum IL-5 and IL-13 were the two best, followed by EDN as separators of high vs low blood eosinophilia. Periostin did not identify blood or sputum eosinophilia, even after stratification for total IgE, and did not correlate with IL-5, IL-13, eotaxin, or EDN. IL-5 and IL-13 showed strong correlations with AHR and monocyte chemoattractant protein (MCP)-1 with asthma severity and fast LF decline. The presence of high or low expression of MCP-1, eotaxin, and IL-8 identified two separate blood eosinophilia patient clusters linked to asthma severity. CONCLUSION: Serum IL-5 and IL-13 are reliable biomarkers for the blood eosinophilia asthma phenotype. High or low expression of MCP-1, eotaxin, and IL-8 discriminates between eosinophilic asthma severity clusters.

Intense-Field Double Detachment of Electrostatically Bound F(-)(NF3)n Cluster Anions.

The interaction of intense laser pulses with size-selected F(-)(NF3)n clusters is experimentally studied. Intense-field double- and multiple-detachment processes in the isolated atomic F(-) anion and in electrostatically bound F(-)(NF3) dimer and F(-)(NF3)2 trimer systems are directly compared. Both dimer and trimer systems are found to exhibit similar enhancement of the highly nonlinear processes, with respect to the atomic system, as reflected in significantly lower saturation intensities. The dependencies of different product channels as a function of laser peak intensity, polarization ellipticity, and laser pulse shape are presented, indicating an efficient nonrescattering mechanism.

SF6(-) photodetachment near the adiabatic limit.

High sensitivity photodetachment cross-section measurements of SF6(-) are performed near the adiabatic threshold limit. The extraction of adiabatic detachment energy (ADE) from the high sensitivity measurement of the cross-section change as a function of photon energy is discussed. Below the vertical detachment energy a steep 4 orders of magnitude cross-section drop is observed, with cross sections as low as 2 × 10(-6) Å(2) measured for photon energies below 2 eV. The cross-section is fitted with both the expected spectral shape based on recently calculated Frank-Condon overlaps and a phenomenological threshold function. The resulting 1.7 ± 0.02 eV ADE values are significantly higher than previously recommended experimental ADE values obtained based on kinetics modeling, and possible differences between the experimental approaches are discussed.

Absolute photo-destruction and photo-fragmentation cross section measurements using an electrostatic ion beam trap.

We describe a technique to measure absolute photo-induced cross sections for cluster anions stored in an electrostatic ion beam trap (EIBT) with a central deflector. The setup allows determination of total photo-destruction cross sections as well as partial cross sections for fragmentation and electron detachment. The unique properties of this special EIBT setup are investigated and illustrated using small Al(n)(-) clusters.

An affective disorder in zebrafish with mutation of the glucocorticoid receptor.

Upon binding of cortisol, the glucocorticoid receptor (GR) regulates the transcription of specific target genes, including those that encode the stress hormones corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone. Dysregulation of the stress axis is a hallmark of major depression in human patients. However, it is still unclear how glucocorticoid signaling is linked to affective disorders. We identified an adult-viable zebrafish mutant in which the negative feedback on the stress response is disrupted, due to abolition of all transcriptional activity of GR. As a consequence, cortisol is elevated, but unable to signal through GR. When placed into an unfamiliar aquarium ('novel tank'), mutant fish become immobile ('freeze'), show reduced exploratory behavior and do not habituate to this stressor upon repeated exposure. Addition of the antidepressant fluoxetine to the holding water and social interactions restore normal behavior, followed by a delayed correction of cortisol levels. Fluoxetine does not affect the overall transcription of CRH, the mineralocorticoid receptor (MR), the serotonin transporter (Serta) or GR itself. Fluoxetine, however, suppresses the stress-induced upregulation of MR and Serta in both wild-type fish and mutants. Our studies show a conserved, protective function of glucocorticoid signaling in the regulation of emotional behavior and reveal novel molecular aspects of how chronic stress impacts vertebrate brain physiology and behavior. Importantly, the zebrafish model opens up the possibility of high-throughput drug screens in search of new classes of antidepressants.

Effects of molecular rotation in low-energy electron collisions of H3+.

Measurements on the energetic structure of the dissociative recombination rate coefficient in the millielectronvolt range are described for H3+ ions produced in the lowest rotational levels by collisional cooling and stored as a fast beam in the magnetic storage ring TSR (Test Storage Ring). The observed resonant structure is consistent with that found previously at the storage ring facility CRYRING in Stockholm, Sweden; theoretical predictions yield good agreement on the overall size of the rate coefficient, but do not reproduce the detailed structure. First studies on the nuclear spin symmetry influencing the lowest level populations show a small effect different from the theoretical predictions. Heating processes in the residual gas and by collisions with energetic electrons, as well as cooling owing to interaction with cold electrons, were observed in long-time storage experiments, using the low-energy dissociative recombination rate coefficient as a probe, and their consistency with the recent cold H3+ measurements is discussed.

Size-dependent electron-impact detachment of internally cold Cn- and Aln- clusters.

The cross sections for electron detachment of internally cold Cn- and Aln- clusters were measured using an electrostatic ion beam trap fitted with an internal electron target. The measured electron-impact detachment cross sections for the Cn- (n = 1-9) clusters exhibit even-odd oscillations reflecting the binding energy trend, namely, higher cross sections for weaker binding. Surprisingly, however, these cross sections increase on the average with cluster size, n, in spite of the increase in electron binding. In contrast, the Aln- (n = 2-5) clusters follow the known scaling laws for electron detachment. We suggest that the size-dependent polarizability of these clusters is responsible for the observed behavior.

Evidence for subthermal rotational populations in stored molecular ions through state-dependent dissociative recombination.

We demonstrate that the dissociative recombination of D2H+ with low-energy electrons depends on the rotational energy of the molecular ion such that highly excited ions have a larger rate coefficient than colder ones. Observations on an ion beam continuously interacting with electrons at low relative velocity indicate that excited rotational levels are preferentially depleted which, in competition with radiative heating due to blackbody radiation, provides an opportunity for controlling the rotational temperature of stored molecules.

Negative mass instability for interacting particles in a 1D box: theory and application.

We demonstrate that the synchronization effect observed [Pedersen et al., Phys. Rev. Lett. 87, 055001 (2001)]], when a bunch of ions oscillates between two mirrors in an electrostatic ion beam trap, can be explained as a negative mass instability. We derive simple necessary conditions for the existence of a regime in which this dispersionless behavior occurs and demonstrate that in this regime, the ion trap can be used as a high resolution mass spectrometer.

Ion motion synchronization in an ion-trap resonator.

Using a new type of ion trap, we demonstrate that the length of a packet of charged particles oscillating between two electrostatic mirrors will remain constant under special conditions. The effect can be understood in terms of phase synchronization, where, in a rather counterintuitive way, the repulsive Coulomb interaction between the ions actually holds the packet together. Application of this effect for mass spectrometry is discussed.

Molecular and physiological characterisation of a 14-3-3 protein from lily pollen grains regulating the activity of the plasma membrane H+ ATPase during pollen grain germination and tube growth.

A 14-3-3 protein has been cloned and sequenced from a cDNA library constructed from mRNAs of mature pollen grains of Lilium longiflorum Thunb. Monoclonal antibodies (MUP 5 or MUP 15) highly specific against 14-3-3 proteins recognised a 30-kDa protein in the cytoplasmic fraction of many various lily tissues (leaves, bulbs, stems, anther filaments, pollen grains, stigmas) and in other plants (Arabidopsis seedlings, barley recombinant 14-3-3). In addition, 14-3-3 proteins were detected in a microsomal fraction isolated from pollen grains and tubes, and the amount of membrane-bound 14-3-3 proteins as well as the amount of the plasma membrane (PM) H+ ATPase increased during germination of pollen grains and tube growth. No change was observed in the cytoplasmic fraction. A further increase in the amount of 14-3-3 proteins in the microsomal fraction was observed when pollen grains were incubated in germination medium containing 1 microM fusicoccin (FC) whereas the number of 14-3-3s in the cytoplasmic fraction decreased. Fusicoccin also protected membrane-bound 14-3-3 proteins from dissociation after washing with the chaotropic salt KI. Furthermore, FC stimulated the PM H+ ATPase activity, the germination frequency and the growth rate of pollen tubes, thus indicating that a modulation of the PM H+ ATPase activity by interaction with 14-3-3 proteins may regulate germination and tube growth of lily pollen.

Two- and three-body kinematical correlation in the dissociative recombination of H(3)(+).

Fragmentation patterns for dissociative recombination of the triatomic hydrogen molecular ion H(3)(+) in the vibrational ground state have been measured using the storage ring technique and molecular fragment imaging. A broad distribution of vibrational states in the H(2) fragment after two-body dissociation and a large predominance of nearly linear momentum geometries after three-body dissociation are found. The fragmentation results are directly contrasted with Coulomb explosion imaging data on the initial H(3)(+) geometry, compared to existing wave-packet calculations, and considered in the light of a simple physical picture.

Perceptions of physical restraint use and barriers to restraint reduction in a long-term care facility.

The use of restraints in nursing homes has been curtailed in the United States since the passage of the 1987 federal legislation regulating restraint practices. This study used focus groups with administrators and nursing staff in a skilled nursing facility to examine their views of restraints and perceptions of conditions in the nursing home environment that affect restraint use. Although respondents lacked a shared definition of a "restraint," they did identify contextual factors that in combination with resident characteristics produced situations in which restraint use was justified. Implications of these findings for staff education on restraint reduction are discussed.

Functional outcome of cognitively impaired hip fracture patients on a geriatric rehabilitation unit.

OBJECTIVES: To compare outcomes (physical functions and discharge destinations) of cognitively impaired and intact older hip fracture patients, and to identify cognitive skills related to functional gains. DESIGN: Prospective longitudinal study of hip fracture patients treated on an acute inpatient rehabilitation service, with evaluation of functional performance and living status determined at admission and discharge. SETTING: A specialized inpatient geriatric rehabilitation program at Wesley Woods Geriatric Hospital, which is affiliated with Emory University School of Medicine. SUBJECTS: Fifty-eight hip fracture patients, 35 with and 23 without cognitive impairment. MEASUREMENTS: Cognitive functioning measured by the Mattis Dementia Rating Scale (MDRS); functional outcome assessed by the Functional Independence Measure (FIM); comparison of pre-fracture with discharge living environments. MAIN RESULTS: Both cognitively impaired and intact hip fracture patients exhibited similar overall FIM motor improvements as well as functional gains in specific FIM areas measuring self-care, sphincter control, and locomotion (e.g., walking). Cognitively intact patients, however, displayed significantly greater gains in mobility (e.g., transfers) at discharge. Cognitively impaired patients who lived in the community were as likely as intact patients to return to the community. Patients who entered the program at a modified dependence level (FIM 3-5) and achieved motor independence at discharge (FIM 6-7) had higher MDRS initiation/ perseveration and memory scores. CONCLUSIONS: Hip fracture patients with cognitive impairments can achieve positive outcomes as defined by functional improvement and discharge destination. Intensive post-fracture rehabilitation in the early phase of recovery may promote functional independence and a return to the community for older patients at risk for nursing home placement. Future research should examine the long-term maintenance of these improvements and explore how rehabilitation interventions can be altered to enhance outcome.

Linking Treatment to Outcomes through Teams: Building a Conceptual Model of Rehabilitation Effectiveness.

The team approach has been the dominant paradigm in contemporary inpatient medical rehabilitation. In this article, a conceptual model of treatment effectiveness is presented that links characteristics of the hospital organization, treatment, and participants to patient outcomes through the treatment team. The proposed mechanism of team process is founded on the interprofessional relations and "personality" (or social climate) of the team. The process of team care emerges from team leadership and managerial practices. The dimensions of team process that are hypothesized to influence patient outcomes are highlighted.

Predicting stroke inpatient rehabilitation outcome using a classification tree approach.

A classification tree, a nonparametric statistical analysis, was used to develop decision rules to predict a favorable inpatient stroke rehabilitation outcome. Descriptive and functional status data collected on admission from 225 patients were the predictor variables. Favorable outcome was defined as having met three criteria: discharged to community, survival greater than 3 months postdischarge, and no more than minimal physical assistance required in functional activities on discharge. The classification tree correctly classified 88% of the sample using only four of the predictor variables (level of independence in Toilet Management, Bladder Management, and Toilet Transfer, and adequacy of Financial Resources). The cross validation error rate was 18%. The advantages of the classification tree approach over parametric methods are that it is desirable for ordinal data, it readily identifies the interactions among predictor variables, the results are easily communicated, and it provides additional insights into the factors that predict outcome.

The rehabilitation team: staff perceptions of the hospital environment, the interdisciplinary team environment, and interprofessional relations.

Although inpatient rehabilitation is an interdisciplinary activity organized around a treatment team, there is a limited understanding of the workings of the interdisciplinary process. To elucidate staff perceptions of key aspects of the rehabilitation treatment process, we surveyed staff (n = 113) from selected inpatient teams. The staff completed social psychological instruments that measure perceptions of the hospital environment (The Ward Atmosphere Scale [WAS]), the team's environment (the Group Environment Scale [GES]), and interprofessional relations (Interprofessional Perception Scale [IPS]). Rehabilitation staff generally endorse the team approach, but express concerns over professional boundaries. Interprofessional difficulties seemed to be independent of team membership or professional training. Compared with published data from other settings, rehabilitation teams resembled task-oriented groups, but showed significant differences across teams in their perceptions of the team and hospital environments. The task-oriented character of rehabilitation teams, team-specific characteristics, and discord in interprofessional relationships may need to be considered in studies of rehabilitation teams effectiveness.

Stroke inpatient rehabilitation: a comparison across age groups.

OBJECTIVE: To examine and compare the inpatient stroke rehabilitation experience of older adults (> or = 75 years) with that of young adults (< 65 years) and young-old adults (65-74 years). DESIGN: Cross-sectional descriptive study. SETTING: A large university-affiliated free-standing rehabilitation hospital. PARTICIPANTS: 260 adults who were admitted to inpatient stroke rehabilitation with a primary diagnosis of recent (< 120 days) stroke (ICD9 430-436). VARIABLES: Demographic data, diagnosis, time between stroke onset and rehabilitation admission, discharge disposition, and functional status on admission and discharge were obtained from the patient's medical record. Treatment intensity and type, length of stay, and primary payment source data were obtained from the patient's billing record. Three-month mortality data were available from the hospital's routine follow-up survey. MAIN RESULTS: Compared with the younger adults (< 65 yrs and 65-75 years), the older adults (> or = 75 years) were admitted to rehabilitation earlier and with comparable cognitive but poorer motor function. Rehabilitation treatment intensity (per day) and type were similar across age groups, but the older adults (> or = 75 years) had significantly shorter rehabilitation stays. Three-month survival was comparable across age groups, but the older adults (> or = 75 years) had poorer motor function at discharge and were more often discharged to a nursing home or required a paid caregiver. CONCLUSIONS: Age-associated factors may influence inpatient stroke rehabilitation referral, treatment, and outcome, particularly for patients over age 75. The cumulative effects of frailty and co-morbid disease upon stroke disability and treatment are possible explanations for the findings. The study provides evidence of a need for further investigation of stroke rehabilitation strategies for adults over 75 years old.

The critical path method in stroke rehabilitation: lessons from an experiment in cost containment and outcome improvement.

This study tested the effects of a project network technique called the Critical Path Method (CPM) on the costs and outcomes of inpatient team stroke rehabilitation. On admission to a large, academic, inpatient rehabilitation hospital adults who had a recent (< 120 days) stroke were randomly assigned to receive rehabilitation services from a team trained in CPM (N = 53) or from usual care teams (N = 68). Results showed no significant difference between groups in length of stay, hospital charges, or functional status at discharge. CPM may be effective in patient care services that are less influenced by specialization, professional issues, and external regulation and in settings where patient outcomes are relatively fixed and predictable, and medical care is integrated across institutions.

Treatment of early-morning hyperglycemia in type 1 diabetics with amorphous zinc insulin (Semilente) at bedtime.

Fasting hyperglycemia in insulin-dependent diabetic patients (IDDM) treated according to the basal-bolus principle may be due to the fact that currently available neutral protamine Hagedorn (NPH) insulin preparations do not sufficiently meet the increased insulin need in the second part of the night. In the present study, it was investigated whether the amorphous zinc insulin Semilente can be used to control fasting hyperglycemia in IDDM patients. Ten type 1 diabetic patients with persistent fasting hyperglycemia (> 10 mmol/l) participated in the double-blind randomized cross-over trial with 2 10-day treatment periods. Night profiles of blood glucose and free insulin concentrations were determined at the end of each treatment period. Three doses of regular insulin were given before the meals and NPH insulin and Semilente at 10.00 p.m. Nighttime blood glucose and insulin profiles were different under the treatment with Semilente and NPH insulin. Injection of Semilente at bedtime resulted in higher insulin and lower blood glucose values during the second part of the night (p < 0.001 versus Semilente by ANOVA). Semilente injected at bedtime can prevent the early-morning rise in blood glucose in type I diabetic patients.