On the surface tension of fluctuating quasi-spherical vesicles

We calculate the stress tensor for a quasi-spherical vesicle and we thermally average it in order to obtain the actual, mechanical, surface tension $\tau$ of the vesicle. Both closed and poked vesicles are considered. We recover our results for $\tau$ by differentiating the free-energy with respect to the proper projected area. We show that $\tau$ may become negative well before the transition to oblate shapes and that it may reach quite large negative values in the case of small vesicles. This implies that spherical vesicles may have an inner pressure lower than the outer one.Comment: To appear in Eur. Phys. J. E, revised versio

Phase Transitions And Spatially Ordered Counterion Association In Ionic-lipid Membranes: A Statistical Model.

We propose a statistical model to account for the gel-fluid anomalous phase transitions in charged bilayer- or lamellae-forming ionic lipids. The model Hamiltonian comprises effective attractive interactions to describe neutral-lipid membranes as well as the effect of electrostatic repulsions of the discrete ionic charges on the lipid headgroups. The latter can be counterion dissociated (charged) or counterion associated (neutral), while the lipid acyl chains may be in gel (low-temperature or high-lateral-pressure) or fluid (high-temperature or low-lateral-pressure) states. The system is modeled as a lattice gas with two distinct particle types--each one associated, respectively, with the polar-headgroup and the acyl-chain states--which can be mapped onto an Ashkin-Teller model with the inclusion of cubic terms. The model displays a rich thermodynamic behavior in terms of the chemical potential of counterions (related to added salt concentration) and lateral pressure. In particular, we show the existence of semidissociated thermodynamic phases related to the onset of charge order in the system. This type of order stems from spatially ordered counterion association to the lipid headgroups, in which charged and neutral lipids alternate in a checkerboard-like order. Within the mean-field approximation, we predict that the acyl-chain order-disorder transition is discontinuous, with the first-order line ending at a critical point, as in the neutral case. Moreover, the charge order gives rise to continuous transitions, with the associated second-order lines joining the aforementioned first-order line at critical end points. We explore the thermodynamic behavior of some physical quantities, like the specific heat at constant lateral pressure and the degree of ionization, associated with the fraction of charged lipid headgroups.8403190

Relationships between technical efficiency and the quality and costs of health care in Italy†

Objectives This paper reports the measurement of technical efficiency of Tuscan Local Health Authorities and its relationship with quality and appropriateness of care. Design First, a bias-corrected measure of technical efficiency was developed using the bootstrap technique applied to data envelopment analysis. Then, correlation analysis was used to investigate the relationships among technical efficiency, quality and appropriateness of care. Setting and Participants These analyses have been applied to the Local Health Authorities of Tuscany Region (Italy), which provide not only hospital inpatient services, but also prevention and primary care. All top managers of Tuscan Local Health Authorities were involved in selection of the inputs and outputs for calculating technical efficiency. Main Outcome Measures The main measures used in this study are volume, quality and appropriateness indicators monitored by the multidimensional performance evaluation system developed in the Tuscany Region. Results On average, Tuscan Local Health Authorities experienced 14(%) of bias-corrected inefficiency in 2007. Correlation analyses showed a significant negative correlation between per capita costs and overall performance. No correlation was found in 2007 between technical efficiency and overall performance or between technical efficiency and per capita costs. Conclusions Technical efficiency cannot be considered as an extensive measure of healthcare performance, but evidence shows that Tuscan Local Health Authorities have room for improvement in productivity levels. Indeed, correlation findings suggest that, to pursue financial sustainability, Local Health Authorities mainly have to improve their performance in terms of quality and appropriateness

Effects of anti-IL5 biological treatments on blood IgE levels in severe asthmatic patients: A real-life multicentre study (BIONIGE)

Background: Mepolizumab and benralizumab are clinically effective biological treatments for severe eosinophilic asthmatic patients by hampering eosinophilic inflammation. The effects of these compound on the immunoglobulin (Ig)E T2 component are virtually unknown. Objectives: To evaluate the change in total IgE levels at 4 ± 2 months after initiation of the mepolizumab (primary outcome) or benralizumab. When available, the changes of blood inflammatory cell counts, lung function and asthma control test (ACT) were also assessed and correlated with changes in total IgE levels. Methods: Observational, retrospective, multicentre, cohort study. Severe eosinophilic atopic asthmatic patients treated with mepolizumab or benralizumab were included in the analysis. Results: Three-month treatment (on average) with mepolizumab (n = 104) or benralizumab (n = 82) resulted in significantly higher reduction of blood eosinophil and basophil levels in patients treated with benralizumab compared to mepolizumab. Mepolizumab did not significantly modified the levels of blood total IgE during the study period, whereas benralizumab significantly reduced (−35%, p < 0.001) total blood IgE levels. In patients treated with benralizumab the reduction of blood total Ig-E levels correlated with the reduction of blood basophils (but not eosinophils) and weakly with the improvement of asthma control. Conclusion: Benralizumab but not mepolizumab, treatment led to a significant reduction of circulating IgE level. The study provides different and specific mechanisms of action for anti-IL5-pathway treatments

Polypeptide-grafted macroporous polyHIPE by surface-initiated N-Carboxyanhydride (NCA) polymerization as a platform for bioconjugation

A new class of functional macroporous monoliths from polymerized high internal phase emulsion (polyHIPE) with tunable surface functional groups was developed by direct polypeptide surface grafting. In the first step, amino-functional polyHIPEs were obtained by the addition of 4-vinylbenzyl or 4-vinylbenzylphthalimide to the styrenic emulsion and thermal radical polymerization. The obtained monoliths present the expected open-cell morphology and a high surface area. The incorporated amino group was successfully utilized to initiate the ring-opening polymer- ization of benzyl-L-glutamate N-carboxyanhydride (BLG NCA) and benzyloxycarbonyl-L-lysine (Lys(Z)) NCA, which resulted in a dense homogeneous coating of polypeptides throughout the internal polyHIPE surfaces as confirmed by SEM and FTIR analysis. The amount of polypeptide grafted to the polyHIPE surfaces could be modulated by varying the initial ratio of amino acid NCA to amino-functional polyHIPE. Subsequent removal of the polypeptide protecting groups yielded highly functional polyHIPE-g-poly(glutamic acid) and polyHIPE-g- poly(lysine). Both types of polypeptide-grafted monoliths responded to pH by changes in their hydrohilicity. The possibility to use the high density of function (−COOH or −NH2) for secondary reaction was demonstrated by the successful bioconjugation of enhanced green fluorescent protein (eGFP) and fluorescein isocyanate (FITC) on the polymer 3D-scaffold surface. The amount of eGFP and FITC conjugated to the polypeptide-grafted polyHIPE was significantly higher than to the amino- functional polyHIPE, signifying the advantage of polypeptide grafting to achieve highly functional polyHIPEs

Australia-modified Karnofsky Performance Scale and physical activity in COPD and lung cancer: an exploratory pooled data analysis

Objectives: Patient-relevant measures of functional status are required in chronic obstructive pulmonary disease (COPD) and lung cancer in clinical practice and research. We explored the relationship between the Australia-modified Karnofsky Performance Scale (AKPS) and measures of functional capacity and physical activity in these patient groups. Methods: Pooled clinical trial data were analysed to explore the relationship between AKPS and average daily steps (ADS), 6 min walk distance (6MWD), and body mass index, airflow obstruction, dyspnoea and exercise score (COPD group). Receiver operator characteristic curves were produced to compare sensitivity and specificity of cut-offs (no dependency >70, high dependency 70, the optimal ADS cut-points were COPD, 3342 steps (AUC 0.88, 95% CI 0.79 to 0.97, sensitivity 82%, specificity 76%), and lung cancer, 3380 steps (AUC 0.72, 95% CI 0.64 to 0.81, sensitivity 61%, specificity 74%), and for 6MWD (COPD only) 242 m (AUC 0.72, 95% CI 0.63 to 0.81, sensitivity 73%, specificity 34%). Conclusions: An AKPS score is strongly related to ADS in people with COPD and lung cancer. The AKPS may be useful in clinical practice and research to indicate levels of physical activity where ADS and 6 min walk test are not possible. Longitudinal data are needed to confirm these findings

The role of diet and exercise and of glucosamine sulfate in the prevention of knee osteoarthritis: Further results from the PRevention of knee Osteoarthritis in Overweight Females (PROOF) study

Background and objectives: The PRevention of knee Osteoarthritis in Overweight Females (PROOF) study (ISRCTN 42823086) described a trend for a decrease in the incidence of knee osteoarthritis (OA) by a tailored diet and exercise program (DEP) or by oral glucosamine sulfate in women at risk for the disease, using a composite clinical and/or radiological outcome. The aim of this updated post-hoc analysis was to re-assess the results according to more precise techniques and take advantage of the 2×2 factorial design. Methods: A total of 407 overweight (BMI ≥ 27 kg/m2) women of 50-60 years of age with no diagnosis of knee OA were randomized to: (1) no DEP + placebo (Control, N = 102), (2) DEP + placebo (DEP, N = 101), (3) glucosamine sulfate + no DEP (GS, N = 102), and (4) DEP + glucosamine sulfate (DEP + GS, N =102) and followed for 2.5 years, with standardized postero-anterior, semiflexed (MTP) view knee radiographs at baseline and end of the study. DEP consisted of a tailored low fat and/or low caloric diet and easy to implement physical activities. Glucosamine was given as oral crystalline glucosamine sulfate 1500 mg once daily, double-blinded vs. placebo. Incident knee OA was defined as radiographic progression of ≥1 mm minimum joint space narrowing (mJSN) in the medial tibiofemoral compartment, as previously assessed by the visual (manual) technique and by a new semi-automated method. Logistic regression analysis was used to calculate the odds ratio for the effect of the interventions. Results: After 2.5 years, 11.8% of control subjects developed knee OA. This incidence was decreased with glucosamine sulfate, either alone or in combination with the DEP, but not by the DEP alone. Since there was no statistical interaction between treatments, the 2×2 factorial design allowed analysis of patients receiving glucosamine sulfate (= 204) vs. those not receiving it (= 203), similarly for those on the DEP (= 203) or not (= 204). Glucosamine sulfate significantly decreased the risk of developing knee OA: odds ratio (OR) = 0.41 (95% CI: 0.20-0.85, P = 0.02) by the manual JSN assessment method and OR = 0.42 (95% CI: 0.20-0.92, P = 0.03) by the semi-automated technique. Conversely, there was no decrease in risk with the DEP. Conclusions: Glucosamine sulfate decreased the risk of developing radiographic knee OA over 2.5 years in overweight, middle-aged women at risk, as determined by medial mJSN progression. Conversely a tailored diet and exercise program exerted no preventive effect, possibly because of the lower than expected effect on weight loss