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• Three symptom cluster classes were identified at each of three time points. • Classes 1 to 3 were designated as low, intermediate , and high symptom burden groups. • People in Classes 1 and 2 at baseline tended to remain in the same class over time. • People in Class 3 at baseline showed greater transition to Class 1 or 2. • CBT-I was significantly associated with movement to a lower symptom burden group. People with chronic obstructive pulmonary disease (COPD) and insomnia experience multiple co-occurring symptoms, but no studies have examined symptom cluster change over time in this population. This study explored longitudinal patterns of symptom cluster profiles for adults with COPD and insomnia and evaluated whether behavioral interventions were associated with changes in symptom cluster profiles. This study included 91 adults with COPD and insomnia who participated in a randomized trial of cognitive behavioral therapy for insomnia (CBT-I) and COPD education. The pre-specified symptom cluster included insomnia, dyspnea, fatigue, anxiety, and depression. Latent profile analysis identified participant groups with distinct symptom cluster profiles at baseline, immediately post-intervention, and at 3-month follow-up; latent transition analysis then estimated the probability of group membership change over time. Multinomial logistic regression was used to determine whether the interventions were associated with changes in symptom cluster profiles. Three groups were identified at each of three time-points: Class 1 (low symptom burden), Class 2 (intermediate), and Class 3 (high). Classes 1 and 2 showed less movement to other classes (16 % and 38 %, respectively), whereas Class 3 showed greater transition (64 %). The CBT-I intervention was significantly associated with movement to a lower symptom burden group (Class 3 to 2 or 2 to 1). CBT-I, with or without COPD education, shows promise as a tailored intervention to reduce symptom burden in the study population. Study findings will facilitate development of interventions to reduce the severity of multiple co-occurring symptoms in people with COPD and insomnia. Registry: ClinicalTrials.gov; Name: A Behavioral Therapy for Insomnia Co-existing with COPD; Identifier: NCT01973647. [ABSTRACT FROM AUTHOR]

Copyright of Revista Española de Cardiología (18855857) is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Total shoulder arthroplasty with a humeral head resurfacing (HHR) component and an inlay glenoid (OVOMotion; Arthrosurface) is a successful treatment option for patients with advanced glenohumeral arthritis, an intact rotator cuff, and adequate proximal humeral bone stock. In patients with poor proximal humeral bone, historically stemmed humeral components have been used instead of HHR. However, strategies can be used to successfully optimize HHR implant fixation in suboptimal bone without converting to stemmed implants or in surgical centers where stemmed prostheses are not available. This Technical Note describes 3 techniques—upsizing the humeral taper post, using humeral autograft, and cementation—to improve humeral implant fixation in patients with suboptimal bone stock when using the Arthrosurface OVOMotion implant. [Display omitted] [ABSTRACT FROM AUTHOR]

Copyright of Revista Española de Cardiología (18855857) is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Postpartum pelvic prolapse was observed in a female C57BL/6 mouse reared for the purpose of breeding at the animal house facility at NISER, Bhubaneswar, India. Whereas the terminal portion of the prolapsed mass was inflamed and appeared red in color, the rest of the portion appeared swollen and edematous. Reoccurrence of prolapse was observed on manual reduction. An alternative approach of hydropropulsion using weak antiseptic solution in cold water was used successfully for the management of prolapse in the mouse. The technique was observed to be easy and effective without any complication of recurrence of prolapse. The technique is less traumatic and involves minimal handling of the prolapsed mass, and hence may be helpful in preventing common complications related to manual reduction of prolapsed tissue such as congestion rupture and risk of infection. Thus, the technique can be effectively used by veterinarians for the management of pelvic prolapse in small pets or laboratory animals such as mice, rats, guinea pigs, and hamsters. [ABSTRACT FROM AUTHOR]

Background Sublingual allergen immunotherapy (SLIT) has been demonstrated to be both clinically efficacious and safe. However, in line with the current regulatory guidance from the European Medicines Agency, allergen immunotherapy (AIT) products must demonstrate their efficacy and safety in pivotal phase III trials for registration. Objective We sought to investigate the efficacy and safety of sublingual high-dose liquid birch pollen extract (40,000 allergy units native [AUN]/mL) in adults with birch pollen allergy. Methods A randomized, double-blind, placebo-controlled, parallel-group multicenter trial was conducted in 406 adult patients with moderate-to-severe birch pollen-induced allergic rhinoconjunctivitis with or without mild-to-moderate controlled asthma. Treatment was started 3 to 6 months before the birch pollen season and continued during the season in 40 clinical study centers in 5 European countries. For primary end point assessment, the recommended combined symptom and medication score of the European Academy of Allergy and Clinical Immunology was used. Secondary end points included quality-of-life assessments, immunologic parameters, and safety. Results Primary efficacy results demonstrated a significant (P <.0001) and clinically relevant (32%) reduction in the combined symptom and medication score compared with placebo after 3 to 6 months of SLIT. Significantly better rhinoconjunctivitis quality-of-life scores (P <.0001) and the patient's own overall assessment of his or her health status, including the visual analog scale score (Euro Quality of Life Visual Analogue Scale; P =.0025), were also demonstrated. In total, a good safety profile of SLIT was observed. Conclusion This study confirmed both the clinical efficacy and safety of a sublingual liquid birch pollen extract in adults with birch pollen allergy in a pivotal phase III trial (EudraCT: 2013-005550-30; ClinicalTrials.gov: NCT02231307). [ABSTRACT FROM AUTHOR]

Introduction: Fusion of therapeutic agents to Elastin-like Polypeptide (ELP) is a novel drug delivery strategy for prevention of placental drug transfer. Previous studies have used a 60 kDa ELP tag for this purpose. However, placental transfer of ELP may be size dependent. The goal of this study was to measure the effects of ELP polymer size on pharmacokinetics, biodistribution, and placental transfer of ELP.Methods: Three ELPs ranging from 25 to 86 kDa (4.1-6.8 nm hydrodynamic radius) were fluorescently labeled and administered by i.v. bolus to pregnant Sprague Dawley rats on gestational day 14. Plasma levels were monitored for 4 h, organ levels and placental transfer determined by ex vivo fluorescence imaging, and placental localization determined by confocal microscopy.Results: Increasing ELP size resulted in slower plasma clearance and increased deposition in all major maternal organs, except in the kidneys where an opposite effect was observed. Placental levels increased with an increase in size, while in the pups, little to no ELP was detected.Discussion: Pharmacokinetics and biodistribution of ELPs during pregnancy are size dependent, but all ELPs tested were too large to traverse the placental barrier. These studies verify that ELP fusion is a powerful method of modulating half-life and preventing placental transfer of cargo molecules. The tunable nature of the ELP sequence makes it ideal for drug delivery applications during pregnancy, where it can be used to target drugs to the mother while preventing fetal drug exposure. [ABSTRACT FROM AUTHOR]

Abstract Background The liver is the most common site of colorectal liver metastases (CRLM) and surgical resection improves overall survival in selected patients. Here, we investigate outcomes and relevant prognostic factors after repeated hepatic resections for CRLM. Methods From a prospective database, 578 patients who underwent 788 resections of colorectal liver metastases were included into this study. In total, 169 patients underwent a second and 41 patients had a third operation due to intrahepatic metastatic recurrence. Univariate and multivariate analyses were performed to determine prognostic risk factors. Results 5-year overall survival was 36.7% (95% CI: 30.2%; 43.2%) and 10-year survival was 20.3% (95% CI: 7.6%; 33.0%) in patients undergoing single resection. In patients undergoing a second or third resection, 5- and 10-year survival rates were 56.6% (95% CI: 45.0%; 68.2%) and 21.9% (95% CI: 6.8%; 37.0%) or 53.2% (95% CI: 32.4%; 74.0%) and 25.4%, respectively. In patients undergoing single resection, established markers (number, size and pattern of CRLM [p = 0.030/0.015/<0.001], R-status [p = 0.001], surgical/medical complications [p = 0.001/0.008], CEA-level [p = 0.001] and Fong-Score [p = 0.02]) were significantly associated with survival. In patients undergoing three resections, the only predictive markers were pT-stage of the primary tumor in univariate analysis (p = 0.013) and metachronous metastasis and medical complications in multivariate analysis (p = 0.001/0.025). The Fong-Score had no predictive value in patients undergoing two (p = 0.08) or three (p = 0.7) resections. Conclusion Established prognostic indicators are not applicable in patients undergoing repeated CRLM resection. In a highly-selected group of patients, repeated hepatic resections can be performed safely with favorable long-term outcomes. [ABSTRACT FROM AUTHOR]

The splattering of raindrops is a very important factor in the spread of plant diseases from the Septoria group. The spreading mechanism of this disease via spores is observable particularly during short and violent storms. The methods used currently to forecast Septoria infection are based mainly on the climate condition and the calendar measurements, primarily taking into consideration the disease cycles. These measurements, however, do not take into account the most important factor: the splattering of raindrops as a method of transporting spores onto higher parts of the plants. If this factor is ignored, the forecasting models are flawed and have little correlation with the real development of a disease epidemic. The method presented in this study uses an electric field to measure the range of dispersal and number of splatter particles. This is achieved by means of a measuring system that allows for accurate and reliable measurement of the dispersal range of splashed raindrops. These raindrops scatter the spores and transmit the infection to higher parts of the plants as well as to neighboring plants. [ABSTRACT FROM AUTHOR]

Objective Upon activation, G protein coupled receptors (GPCRs) associate with heterotrimeric G proteins at the plasma membrane to initiate second messenger signaling. Subsequently, the activated receptor experiences desensitization, internalization, and recycling back to the plasma membrane, or it undergoes lysosomal degradation. Recent reports highlight specific cases of persistent cyclic AMP generation by internalized GPCRs, although the functional significance and mechanistic details remain to be defined. Cyclic AMP generation from internalized Glucagon-Like Peptide-1 Receptor (GLP-1R) has previously been reported from our laboratory. This study aimed at deciphering the molecular mechanism by which internalized GLP-R supports sustained cyclic AMP generation upon receptor activation in pancreatic beta cells. Methods We studied the time course of cyclic AMP generation following GLP-1R activation with particular emphasis on defining the location where cyclic AMP is generated. Detection involved a novel GLP-1 conjugate coupled with immunofluorescence using specific endosomal markers. Finally, we employed co-immunoprecipitation as well as immunofluorescence to assess the protein–protein interactions that regulate GLP-1R mediated cyclic AMP generation at endosomes. Results Our data reveal that prolonged association of G protein α subunit Gαs with activated GLP-1R contributed to sustained cyclic AMP generation at Rab 5 endosomal compartment. Conclusions The findings provide the mechanism of endosomal cyclic AMP generation following GLP-1R activation. We identified the specific compartment that serves as an organizing center to generate endosomal cyclic AMP by internalized activated receptor complex. [ABSTRACT FROM AUTHOR]

This paper proposes a framework for the realisation of business value during the deployment of enterprise information systems (EIS). Current research establishes that investments in IT can create value, but gives limited guidance on the mechanics of how to manage the realisation of value related to IT. This paper draws on case studies and in-depth interviews to add the granularity needed to guide decision makers and project teams in planning and realizing value during EIS deployment. The framework proposes a holistic approach in which combined investments in EIS and organisation enables efficient and effective processes that in turn drive customer and financial performance. [ABSTRACT FROM AUTHOR]

Various cohesive zone models have been applied to simulate fatigue crack growth. Here, an extended model is presented that allows the prediction of damage evolution under monotonic as well as cyclic loading conditions. The proposed damage evolution equation incorporates a local endurance limit which has been proven to enable the description of the relation of crack extension rate vs. cyclic load in all stages. This study addresses the predictive capabilities of the model with respect to fatigue life under homogeneous stress-based loading. The influences of the model parameters on life-time and endurance limit are investigated. Nu- merical simulations with variable load amplitude demonstrate non-linear damage accumulation characteristics which qualitatively match experimental observations. [ABSTRACT FROM AUTHOR]

Several analytical and numerical studies of inverse analysis are performed to verify the feasibility and accuracy of the proposed K-sensor. At first, the application to cracks in sheets under in-plane stresses is investigated and compared with the analytical solution for the GRIFFITH's crack under mixed mode. It was found that the convergence radius, where the electrodes have to be placed, must be smaller than half of the crack length, which is sufficient for real cracks of several millimeters. The obtained accuracy of crack tip location and ( K I , K II )-factors is better than 1%. Second, the technique is applied to cracks in thin-walled plates of KIRCHHOFF type under bending and torsion moments. In this case, the plate intensity factors ( k 1 , k 2 ) are of interest. Again, the inverse identification procedure is studied by synthetic analytical and numerical solutions of simple crack configurations. Due to the assumptions of the KIRCHHOFF plate model, the sensors have to be placed outside a radius of 3 times plate thickness h . The obtained accuracy in position and intensity factors is quite sufficient as well. The practical realization of the K -factor sensor requires good electric signal measurement and amplification. Its experimental testing on components is ongoing work. [ABSTRACT FROM AUTHOR]

Typical engineering metals exhibit a change of the failure mechanism with decreasing temperature. In the range of room temperature a ductile mechanism is observed. Thereby, voids nucleate, grow by plastic deformations of the surrounding matrix and finally the voids coalesce. In contrast in the low temperature regime, cleavage failure occurs, a mechanism which is associated with macroscopically brittle behavior. In the present study the crack initiation and propagation is investigated in the ductile-brittle transition region by means of a microscopic model. The voids in the process zone in front of the crack tip are resolved discretely. Possible void growth in the surrounding plastic zone, which may induce an important shielding effect, is taken into account in a homogenized way by means of the GTN-model. In contrast to comparable studies in the literature not only cleavage crack initiation is addressed but the material degradation by the cleavage mechanism is incorporated explicitly by means of a cohesive zone model. The limit case of small- scale yielding is investigated. This model allows to simulate all stages of crack initiation and propagation at all temperatures. A systematic study of the effects of the model parameters is performed. [ABSTRACT FROM AUTHOR]

Within this paper an extended strip-yield model for the simulation of fatigue crack growth in nodular cast iron under variable amplitude loading is presented. The model is based on the conventional strip-yield model and by using an additional boundary condition the formerly observed crack acceleration effects after applied overloads can be described. A comparison of experimental results and simulation shows the applicability of the extended strip-yield model for single spike overloads as well as for random load sequences. [ABSTRACT FROM AUTHOR]

The software system ProCrack, a Python-based tool for the automated finite element simulation of fatigue crack growth in arbitrarily loaded three-dimensional components is presented. The preprocessing and the finite element analysis of the cracked structure are done using the commercial software system Abaqus. The analysis of fatigue crack growth is carried out within the framework of the classical linear elastic fracture mechanics. A submodelling technique in combination with the interaction integral technique is used to calculate the range of the stress intensity factors. The application examples illustrate the capability and performance of the simulation tool ProCrack. [ABSTRACT FROM AUTHOR]

The strength and fracture toughness of small ceramic discs under biaxial flexural load are investigated with two different miniaturized test methods: the small punch test (SPT) and the ball-on-three-balls test (B3B). An alumina ceramic was chosen as sample material. While the specimen geometries are identical for both tests, the experimental set-ups and the stress fields are different. First, the Weibull parameters of strength have been estimated. Second, the fracture toughness is evaluated with an adaption of the surface crack in flexure (SCF) method. The discs are prepared with artificial surface cracks whose sizes have to be measured. The evaluation of stresses and stress intensity factors is based on finite element calculations. [ABSTRACT FROM AUTHOR]

The phase transformation in austenitic TRIP-steels contributes to favourable mechanical properties and may affect their fracture behavior. Therefore, the influence of the phase transformation on the crack driving force is investigated. The concept of material forces is applied to a casted CrMnNi TRIP-steel by incorporating inelastic material and transformation behavior via the material model. The resultant material force expression for the near tip crack driving force is presented and evaluated by summing up nodal material forces. The advantage of this method is the separated calculation of material forces due to dissipation by plastic deformation and phase transformation as well as the material force acting directly at the crack tip. The TRIP-effect implies a considerable contribution to the material forces, i.e. the driving force for crack propagation is reduced, which indicates a shielding effect. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic idiopathic urticaria/chronic spontaneous urticaria (CIU/CSU) often continue to experience symptoms despite receiving standard-of-care therapy with H1-antihistamines along with 1 or more add-on therapies. Objectives: We sought to evaluate the safety and efficacy of 24 weeks of treatment with omalizumab in patients with persistent CIU/CSU despite treatment with H1-antihistamines at up to 4 times the approved dose plus H2-antihistamines, leukotriene receptor antagonists, or both. Methods: In this phase III study patients were randomized to receive 6 subcutaneous injections at 4-week intervals of either 300 mg of omalizumab or placebo, followed by a 16-week observation period. The primary objective of the study was to evaluate the overall safety of omalizumab compared with placebo. Efficacy (itch severity, hive, and urticaria activity scores) was evaluated at weeks 12 and 24. Results: The overall incidence and severity of adverse events and serious adverse events were similar between omalizumab and placebo recipients; the safety profile was consistent with omalizumab in patients with allergic asthma. At week 12, the mean change from baseline in weekly itch severity score was −8.6 (95% CI, −9.3 to −7.8) in the omalizumab group compared with −4.0 (95% CI, −5.3 to −2.7) in the placebo group (P < .001). Significant improvements were seen for additional efficacy end points at week 12; these benefits were sustained to week 24. Conclusion: Omalizumab was well tolerated and reduced the signs and symptoms of CIU/CSU in patients who remained symptomatic despite the use of H1-antihistamines (up to 4 times the approved dose) plus H2-antihistamines, leukotriene receptor antagonists, or both. [Copyright &y& Elsevier]

Copyright of Revue Francaise d'Allergologie is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Allergic rhinitis (AR) and asthma represent global health problems for all age groups. Asthma and rhinitis frequently coexist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) was initiated during a World Health Organization workshop in 1999 (published in 2001). ARIA has reclassified AR as mild/moderate-severe and intermittent/persistent. This classification closely reflects patients'' needs and underlines the close relationship between rhinitis and asthma. Patients, clinicians, and other health care professionals are confronted with various treatment choices for the management of AR. This contributes to considerable variation in clinical practice, and worldwide, patients, clinicians, and other health care professionals are faced with uncertainty about the relative merits and downsides of the various treatment options. In its 2010 Revision, ARIA developed clinical practice guidelines for the management of AR and asthma comorbidities based on the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. ARIA is disseminated and implemented in more than 50 countries of the world. Ten years after the publication of the ARIA World Health Organization workshop report, it is important to make a summary of its achievements and identify the still unmet clinical, research, and implementation needs to strengthen the 2011 European Union Priority on allergy and asthma in children. [Copyright &y& Elsevier]

Summary: Background: Neutrophil elastase (NE) is implicated in chronic obstructive pulmonary disease (COPD). AZD9668 is a reversible and selective inhibitor of NE, well tolerated at doses of 60mg bid during Phase I/IIa development. Methods: This 12-week, randomised, double-blind, placebo-controlled, Phase IIb, trial (NCT01023516), investigated the efficacy and safety of AZD9668 (60mg bid) versus placebo in patients with symptomatic COPD and a history of exacerbation receiving maintenance budesonide/formoterol. Primary outcome variable: forced expiratory volume in one second (FEV1). Secondary endpoints included: post-bronchodilator FEV1, pre- and post-bronchodilator forced vital capacity, FEV6, forced expiratory flow between 25% and 75% of vital capacity and inspiratory capacity; peak expiratory flow and FEV1 measured at home; EXAcerbations of Chronic pulmonary disease Tool and Breathlessness, Cough and Sputum Scores; St George’s respiratory questionnaire for COPD (SGRQ-C) scores; exacerbations; and safety assessments. Results: Six hundred and fifteen patients were randomised: placebo (302), AZD9668 60mg bid (313). AZD9668 showed no effect on lung function: change in mean pre-bronchodilator FEV1 versus placebo was 0.01L (95% confidence interval: −0.03, 0.05; p =0.533). AZD9668 did not significantly improve respiratory signs and symptoms, SGRQ-C score or time to first exacerbation. Adverse events were similar for AZD9668 and placebo. Conclusions: Three months’ treatment with AZD9668 did not improve lung function, respiratory signs and symptoms or SGRQ-C score when added to budesonide/formoterol maintenance therapy in patients with COPD. In the absence of definitive biomarkers of short-term disease progression, further research is needed to determine the optimal duration of studies to evaluate NE inhibitors as disease-modifying agents. [ABSTRACT FROM AUTHOR]

Abstract: Background/Purpose: Peripherally inserted central venous catheters (PICCs) are commonly used for neonatal vascular access. The aim of this study was to look at PICC line complication rates and possible predictors of PICC infection in a neonatal intensive care unit. Method: This was a prospective study of 226 neonates who had PICCs on our neonatal intensive care unit between January 2006 and June 2009. Complete data was available on 218 neonates who had 294 PICC lines. Criteria for catheter-related sepsis was positive blood cultures (peripheral/central) and/or a positive catheter tip culture after removal in the presence of a clinical suspicion of line sepsis. Results: Of 218 neonates, 132 (169 lines) were medical, and 86 (125 lines) were surgical. Our PICC line infection rate was 17 infections per 1000 catheter-days. Surgical neonates had infection rates of 24.8% compared with 18.3% of medical neonates (P < .18). The odds ratio for a PICC infection was 3.1 (95% confidence interval, 1.64-5.87) if the catheter was in situ for 9 days or more, P < .01. Coagulase-negative staphylococcus was isolated from 55 (89%) of 62 blood cultures. Conclusions: Our PICC infection rate was 17 per 1000 catheter-days. The length of catheter stay was the only predictor of PICC infection. [Copyright &y& Elsevier]

Summary: Objectives: To evaluate the effect of beclomethasone/formoterol versus budesonide/formoterol (non-inferiority) and versus formoterol (superiority) in patients with severe stable chronic obstructive pulmonary disease (COPD). Methods: A double-blind, double-dummy, randomised, active-controlled, parallel-group study. After 4 weeks run-in with ipratropium/salbutamol (40/200 μg, three times daily) patients were randomised to receive beclomethasone/formoterol (200/12 μg pressurised metered dose inhaler), budesonide/formoterol (400/12 μg dry powder inhaler) or formoterol (12 μg dry powder inhaler) twice daily for 48 weeks. Co-primary efficacy variables were change from baseline to 48 weeks in pre-dose morning forced expiratory volume in 1 s (FEV1) and mean rate of COPD exacerbations. Results: Of 718 patients randomised, 703 (232 beclomethasone/formoterol, 238 budesonide/formoterol, 233 formoterol) were in the ITT analysis. Improvement in pre-dose morning FEV1 was 0.077 L, 0.080 L and 0.026 L for beclomethasone/formoterol, budesonide/formoterol and formoterol respectively (LS mean from the ANCOVA model). Beclomethasone/formoterol was not inferior to budesonide/formoterol (95% CI of the difference −0.052, 0.048) and superior to formoterol (p = 0.046). The overall rate of COPD exacerbations/patient/year was similar and not statistically significantly different among treatments (beclomethasone/formoterol 0.414, budesonide/formoterol 0.423 and formoterol 0.431). Quality of life and COPD symptoms improved in all groups and use of rescue medication decreased. Safety profiles were as expected and treatments well-tolerated. Conclusions: Beclomethasone/formoterol (400/24 μg) treatment for 48 weeks improved pulmonary function, reduced symptoms compared to formoterol, was safe and well-tolerated in patients with severe stable COPD. Neither of the long-acting β2-agonist/inhaled corticosteroid combinations affected the low exacerbation rate seen in this population. [Copyright &y& Elsevier]

Abstract: Pyroelectric sensors presented in this work are based on polymers from the PVDF family which are comprised of a piezo- and/or pyroelectric polymer thin film capacitor integrated with either high performance organic thin film transistors (OTFTs) or electrochemical transistors (ECTs) acting as impedance converters, signal amplifiers and conditioners. For flexible integration with diverse electronic devices, large area processes such as screen printing applicable for industrial partners have been used for the fabrication of the sensors and ECT’s. With respect to the intended purpose for detection of human body radiation the absorbance of the impinging IR-light is dramatically increased by the application of printed carbon/Pedot topelectrodes, hence meeting the requirements for low-cost large area processibility. Here we present good working integrated sensor devices based on two components, being an organic thin film transitor with a high-k-nanocomposite gate dielectric or a fully printed electrochemical transistor and a PVDF-copolymer based sensor. [ABSTRACT FROM AUTHOR]

Summary: The pathogenetic mechanisms underlying development of persistent inflammation in aspirin (ASA) intolerance are not fully understood. The aim of this study was to determine levels of MCP-3, RANTES, eotaxin, Il-5 and Il-3 in aspirin intolerant asthmatics (AIA) after nasal lysine–aspirin (Lys–ASA) challenge. Twenty AIA and 10 aspirin tolerant controls (ATC) were challenged with saline or 14.4mg of Lys–ASA. Lys–ASA challenge induced clinical symptoms and influx of eosinophils and basophils only in AIA group. Statistically significant higher levels of MCP-3 and RANTES were found in lavages from AIA as compared with ATC (p <0.05 in all time points). Before challenge the average level of MCP-3 was 86.95pg/ml in AIA and 47.61pg/ml in ATC, RANTES levels were 34.20pg/ml in AIA and 17.21pg/ml in ATC and did not change after the challenge in both group. The mean eotaxin’s level was 11.01pg/ml in AIA and 8.03pg/ml in ATC before and increased to 20.06, 26.22pg/ml (4 and 24h in AIA) as compared to 10.51, 14.76pg/ml (4 and 24h in ATC) after the challenge (p <0.05). Interleukin-3 and Il-5 were not detectable. The highest inhibition of eosinophils’ chemotaxis was induced by anti-eotaxin (47% of inhibition), followed by anti-RANTES (29%), anti-MCP-3 (19%) and anti-Il-5 (9%). In summary, we found that persistent inflammation in AIA patients is characterized by overproduction of MCP-3 and RANTES. Lack of increase in MCP-3 and RANTES levels after Lys–ASA challenge suggest that those mediators are involved in chronic rather than acute phase of ASA induced inflammation. [ABSTRACT FROM AUTHOR]

Summary: Objective: To compare the efficacy of ciclesonide (80 μg/day) with fluticasone propionate (200 μg/day) in mild to moderate persistent asthma. Methods: Patients aged 12–75 years and previously treated with low doses of inhaled corticosteroid (fluticasone propionate 250 μg/day or equivalent) entered a 2–4 week run-in period during which only rescue medication was permitted. For inclusion into the double-blind, 24-week treatment period, patients had to show a forced expiratory volume in 1s (FEV1) of 61–90% predicted and a decrease in FEV1 during run-in of ≥10%. Patients (n = 480) were randomized to ciclesonide 80 μg (ex-actuator) once daily in the evening or fluticasone propionate 100 μg (ex-valve) twice daily. The primary efficacy variable was the change from baseline in FEV1. Secondary efficacy variables included asthma control and asthma-specific quality of life. Results: Both treatments significantly increased FEV1 and other lung function variables from baseline (p < 0.0001, both groups, all variables). The least squares mean increases in FEV1 were 0.46L (ciclesonide) and 0.52L (fluticasone propionate); non-inferiority of ciclesonide to fluticasone propionate was demonstrated (p = 0.0002, per-protocol analysis). Five patients in each group experienced asthma exacerbations. Improvements in the percent of days with asthma control (days with no asthma symptoms and no use of rescue medication) and asthma-specific quality of life were comparable between treatments. Conclusions: The study confirmed similar efficacy of ciclesonide 80 μg once daily and fluticasone propionate 100 μg twice daily in mild to moderate persistent asthma. The low dose of ciclesonide was efficacious during long-term treatment. EudraCT number: 2004-001072-39. [Copyright &y& Elsevier]

Background: Allergen-specific immunotherapy (SIT) is the only available potentially curative approach in the management of allergic diseases. Therapies that boost regulatory T cell induction during SIT might further enhance its effectiveness. Objective: The purpose of this study was to assess the effect of montelukast treatment on early clinical and immunologic effects of allergen-specific immunotherapy in children with asthma. Methods: It was a randomized, double-blind, placebo-controlled trial conducted in 36 children with asthma and allergy to house dust mites who required from 400 to 800 μg of inhaled budesonide per day during the 7-month run-in period. Patients were randomly allocated to receive 5 mg montelukast daily (n = 18) or placebo (n = 18) as an addition to inhaled corticosteroid (ICS) treatment during the 3-month build-up phase of SIT, when modification of ICS doses was not allowed. During the 7 months of the maintenance phase of SIT, ICS doses were adjusted to control the asthma symptoms. Results: After 12 months of SIT, a reduction of the median daily ICS dose, necessary to control asthma symptoms, was 16.7% grater in patients from the placebo group than in patients from the montelukast group. Intervention with montelukast significantly impaired the induction of regulatory T lymphocytes. During the build-up phase of SIT, patients in the placebo group frequently experienced an increase in asthma symptoms leading to exclusions from the per protocol population. Conclusion: Our study failed to show a beneficial effect of montelukast on SIT. In fact, quite the opposite occurred: compared with placebo, montelukast intervention led to less effectiveness of SIT. [Copyright &y& Elsevier]

Abstract: During operation, materials or engineering components are subjected to variable amplitude loading (service loadings), which influences the life time considerably. After chemical, morphological and mechanical characterization of nodular cast iron, systematic investigations of the fatigue crack growth behavior were studied under constant and variable amplitude loading. The results under constant amplitude loadings can be described well by the FORMAN/METTU equation (also known as NASGRO equation), whereby the fatigue crack growth behavior exhibits a dependence on the graphite microstructure. Under variable amplitude loading the experiments show that overloads with various overload ratios always exhibit acceleration effects. These acceleration effects affect the accuracy of life time predictions significantly. Hence, the calculation of the remaining service life based on different usual life time prediction models yields non-conservative results. Therefore, an extended strip yield model is applied, which is able to predict the observed crack growth acceleration after overloads. Finally the numerical results are compared with experiments. [Copyright &y& Elsevier]

Background: The efficacy and safety of the 300−index of reactivity (IR) dose of 5-grass-pollen sublingual immunotherapy (SLIT) tablets (Stallergènes, Antony, France) have been demonstrated for the treatment of hay fever in adults. Objective: We sought to assess the efficacy and safety of this tablet in children and adolescents with grass pollen–related allergic rhinitis. Methods: In this multinational, randomized, double-blind, placebo-controlled study, 278 children (5–17 years of age) with grass pollen–related rhinoconjunctivitis (confirmed by means of a positive grass pollen skin prick test response and serum-specific IgE measurement) received once-daily SLIT tablets or placebo. Treatment was initiated 4 months before the estimated pollen season and continued throughout the season. The primary outcome was the rhinoconjunctivitis total symptom score (RTSS), a sum of 6 individual symptom scores: sneezing, runny nose, itchy nose, nasal congestion, watery eyes, and itchy eyes. Secondary end points included rescue medication intake, individual scores, and safety. Results: The intent-to-treat population included 266 children (mean age, 10.9 ± 3.22 years). The RTSS for the 300-IR group was highly significantly different from that of the placebo group (P = .001). The 300-IR group showed a mean improvement for the RTSS of 28.0% over that seen with placebo and a median improvement of 39.3%. Significant differences between the 300-IR and placebo groups were also observed regarding rescue medication score and proportion of days using rescue medication during the pollen season (P = .0064 and P = .0146, respectively). Adverse events were generally mild or moderate in intensity and expected. No serious side effects were reported. Conclusion: Five-grass-pollen SLIT tablets (300 IR) reduce both symptom scores and rescue medication use in children and adolescents with grass pollen–related rhinoconjunctivitis. [Copyright &y& Elsevier]

Background: Exercise-induced bronchoconstriction occurs in a large proportion of children with asthma, limiting everyday activities important for their physical and social development. Objective: The purpose of this randomized, double-blind, placebo-controlled study was to compare the ability of different patterns of antiasthmatic treatment, recommended in childhood asthma, to protect patients from exercise-induced bronchoconstriction. Methods: Children 6 to 18 years of age with atopic asthma were randomized to a 4-week, placebo-controlled, double-blind trial. Patients were randomly allocated to receive daily 200 μg budesonide (twice daily, 100 μg per dose) + 9 μg formoterol (twice daily, 4.5 μg per dose; n = 20); 200 μg budesonide + 5 or 10 mg montelukast (once daily at bedtime; n = 20); 5 or 10 mg montelukast (n = 20); 200 μg budesonide (n = 20); or placebo (n = 20). A standardized treadmill exercise challenge was performed before and after treatment. Results: Exercise-induced bronchoconstriction, reflected by area under the curve for the FEV1 values from exercise over the 20-minute period and by maximum percent fall in FEV1 after exercise, was significantly diminished after 4 weeks in all active treatment groups, and compared with placebo. Exercise-induced bronchoconstriction protection improved more significantly in the budesonide + montelukast and montelukast groups compared with other therapeutic options. Conclusion: These data indicate differences in effects on exercise-induced bronchoconstriction between therapeutic options recommended in childhood asthma. Control of childhood asthma with exercise-induced bronchoconstriction can be obtained by using regular controller treatment. [Copyright &y& Elsevier]

Abstract: Wilde MC, Castriotta RJ, Lai JM, Atanasov S, Masel BE, Kuna ST. Cognitive impairment in patients with traumatic brain injury and obstructive sleep apnea. Objective: To examine the impact of comorbid obstructive sleep apnea (OSA) on the cognitive functioning of traumatic brain injury (TBI) patients. Design: A case-control study. Neuropsychologic test performances of TBI patients with OSA were compared with those who did not have OSA. The diagnosis of OSA was based on standard criteria using nocturnal polysomnography. Setting: Three academic medical centers with level I trauma centers, accredited sleep disorders centers, and rehabilitation medicine programs. Participants: Thirty-five TBI patients who were part of a project that assessed the effect of sleep disorders in a larger sample of consecutively recruited TBI patients. There were 19 patients with TBI and OSA. They were compared with 16 TBI patients without OSA who were comparable in terms of age, education, severity of injury (when available), time postinjury, and Glasgow Coma Scale scores (when available). Interventions: Not applicable. Main Outcome Measures: The Psychomotor Vigilance Test, Rey Complex Figure Test, Rey Auditory Verbal Learning Test, digit span test from the Wechsler Memory Scale–Revised, and finger-tapping test. Results: The TBI patients with OSA performed significantly worse than the non-sleep disordered TBI patients on verbal and visual delayed-recall measures. The groups performed comparably on motor, visual construction, and attention tests. The TBI patients with OSA made more attention lapses (reaction times ≥500ms), but showed comparable fastest and slowest reaction times on a measure of sustained attention. Conclusions: OSA is associated with more impairment of sustained attention and memory in TBI patients. It is possible that early identification and treatment of OSA may improve cognitive, and thus potentially functional, outcomes of TBI patients with this disease. [Copyright &y& Elsevier]

Summary: Adherence to maintenance therapy is often poor in patients with asthma. Simplifying dosing regimens has the potential to improve both adherence and asthma-related morbidity. In this 12-week, randomized, double-blind, double-dummy, parallel-group study, 617 patients with mild to moderate persistent asthma (mean forced expiratory volume in 1s [FEV1] 78.5% predicted) who were not optimally controlled on inhaled corticosteroids (200–500μg/day) were randomized to once-daily budesonide/formoterol (80/4.5μg, 2 inhalations in the evening), twice-daily budesonide/formoterol (80/4.5μg, 1 inhalation), or a corresponding dose of budesonide once-daily (200μg, 1 inhalation in the evening). All patients received budesonide (100μg twice daily) during a 2-week run-in. Changes in mean morning peak expiratory flow (PEF) were similar for od budesonide/formoterol (23.4l/min) and twice-daily budesonide/formoterol (24.1l/min), and both were greater than with budesonide (5.5l/min; both P<0.001). Evening PEF, symptom-free days, reliever-free days, and asthma control days were improved with budesonide/formoterol therapy vs. budesonide (P<0.05 vs. budesonide for all variables). All treatments were well tolerated. Budesonide/formoterol administered once daily in the evening is a convenient treatment regimen that is as effective in improving asthma control as twice-daily dosing in patients with mild to moderate persistent asthma. [Copyright &y& Elsevier]

Objectives: To determine whether a manually adjustable oral mandibular advancement titration appliance (EMA-T) predicts successful long-term treatment with an oral mandibular advancement appliance (MAA). Study design: At an academic medical center, 21 adults with obstructive sleep apnea (AHI > 10 events/hr) performed baseline, titration, and MAA (Klearway) polysomnograms. During the titration polysomnogram with EMA-T, the mandible was advanced until apneas and hypopneas were eliminated or maximum tolerable advancement was reached. Participants then used the MAA at home and, once the mandible was advanced to the amount determined during the titration polysomnogram, a polysomnogram with MAA was performed. Results: Mean AHI at baseline was 33.5 ± 18.3 (SD) events/hr. During the titration polysomnogram, 9 subjects achieved an AHI < 10 and at least a 50% reduction in AHI. None of the subjects met these criteria on the MAA polysomnogram. Conclusions: EMA-T lowered the AHI to efficacious levels in 43% of patients but this acute response did not predict the efficacy of long-term MAA treatment. [Copyright &y& Elsevier]

Stroke is the leading cause of death and disability globally. Sleep disordered breathing (SDB), a potentially modifiable risk factor of stroke, is highly prevalent in stroke survivors. Evidence supports a causal, bidirectional relationship between SDB and stroke. SDB may increase the risk of stroke occurrence and recurrence, and worsen stroke outcome. While SDB is associated with an increased incidence of hypertension and cardiac arrhythmias, both of which are traditional stroke risk factors, SDB is also an independent risk factor for stroke. A number of characteristics of SDB may increase stroke risk, including intermittent hypoxemia, sympathetic activation, changes in cerebral autoregulation, oxidative stress, systemic inflammation, hypercoagulability, and endothelial dysfunction. On the other hand, stroke may also cause new SDB or aggravate preexisting SDB. Continuous positive airway pressure treatment of SDB may have a beneficial role in reducing stroke risk and improving neurological outcome after stroke. The treatment should be considered as early as possible, particularly when SDB is present post-stroke. The goal of this review is to highlight the strong link between SDB and stroke and to raise awareness for practitioners to consider the possibility of SDB being present in all stroke survivors. [ABSTRACT FROM AUTHOR]

Abstract: The adverse effect of shock-wave lithotripsy (SWL) for renal stones on blood pressure is currently defined as its post-treatment increase. On the contrary, we hypothesize that even mild, unilateral renal obstruction initiates an increase in blood pressure. Then, in absence of treatment-induced injury, the stone removal should decrease the blood pressure. We derived the formula to assess the expected change in the mean arterial pressure following relief of renal obstruction without affecting the kidney functions. The predictions were well replicated in the cohort of patients with renal stone treated with parenchyma-saving open surgery, with 6.4mmHg decrease at 3months. On the contrary, in SWL cohort, instead of the expected 4.7mmHg decrease, the blood pressure was unchanged. In conclusion, the absence of decrease in blood pressure is a very common adverse effect of SWL, leading to an epidemiologically significant increase in the risk of arterial vascular events. [Copyright &y& Elsevier]