Background
Systemic allergic reactions are a risk for allergen immunotherapy that utilizes intact allergen preparations. We evaluated the safety, efficacy and immune mechanisms of short‐course ...treatment with adjuvant‐free Lolium perenne peptides (LPP) following a 6‐week dose‐escalation protocol.
Methods
In a prospective, dose‐escalation study, 61 grass pollen–allergic patients received 2 subcutaneous injections of LPP once weekly for 6 weeks. Safety was assessed evaluating local reactions, systemic reactions and adverse events. The clinical effect of LPP was determined by reactivity to the conjunctival provocation test (CPT). Specific IgE, IgG4 and blocking antibodies were measured at baseline (V1), during (V6) and after treatment (V8).
Results
No fatality, serious adverse event or epinephrine use was reported. Mean wheal diameters after injections were <0.6 cm and mean redness diameters <2.5 cm, independent of dose. Transient and mostly mild adverse events were reported in 33 patients. Two patients experienced a grade I and 4 patients a grade II reaction (AWMF classification). At V8, 69.8% of patients became nonreactive to CPT. sIgG4 levels were higher at V6 (8.1‐fold, P < .001) and V8 (12.2‐fold, P < .001) than at V1. The sIgE:sIgG4 ratio decreased at V6 (−54.6%, P < .001) and V8 (−71.6%, P < .001) compared to V1. The absolute decrease in IgE‐facilitated allergen binding was 18% (P < .001) at V6 and 25% (P < .001) at V8.
Conclusion
Increasing doses of subcutaneous LPP appeared safe, substantially diminished reactivity to CPT and induced blocking antibodies as early as 4 weeks after treatment initiation. The benefit/risk balance of LPP immunotherapy remains to be further evaluated in large studies.
Background
A relevant proportion of allergic rhinoconjunctivitis (ARC) patients experience recurrent symptoms after successfully completing allergen immunotherapy (AIT). This prospective, controlled, ...noninterventional study used internationally standardized instruments to determine the clinical effects of a preseasonal, ultra‐short‐course booster AIT on clinical outcome parameters.
Methods
This two‐arm study included patients aged ≥12 years with recurrent grass pollen‐induced seasonal AR who had completed a successful course of any grass pollen AIT at least 5 years before enrolment. Overall, 56 patients received one preseasonal short‐course booster AIT using tyrosine‐absorbed grass pollen allergoids containing the adjuvant monophosphoryl lipid A (MPL®); 51 control patients received symptomatic medication. The combined symptom and medication score (CSMS) was recorded in the (peak) grass pollen season. Furthermore, concomitant (antiallergic) medication use, the patients’ state of health, Mini Rhinoconjunctivitis Quality of Life Questionnaire (MiniRQLQ) results and safety/tolerability of the treatment were assessed.
Results
The CSMS in the peak grass pollen season was significantly lower in the booster AIT group (Δ=38.4%, P<.01). Moreover, significantly more patients in this group used no concomitant antiallergic medication throughout the peak grass pollen season. Twice as many patients in the booster AIT group as in the control group reported having a better state of health than in the preceding season. MiniRQLQ results showed significant differences favouring the booster AIT. The booster AIT was generally well tolerated, with only two patients reporting mild, grade 1 systemic adverse events.
Conclusion
Booster AIT using tyrosine‐absorbed allergoids containing the adjuvant MPL® effectively prevents re‐occurrence of symptoms in patients with grass pollen‐induced ARC.
The objective of this study is to analyze noise patterns during 599 visceral surgical procedures. Considering work-safety regulations, we will identify immanent noise patterns during major visceral ...surgeries. Increased levels of noise are known to have negative health impacts. Based on a very fine-grained data collection over a year, this study will introduce a new procedure for visual representation of intra-surgery noise progression and pave new paths for future research on noise reduction in visceral surgery. Digital decibel sound-level meters were used to record the total noise in three operating theatres in one-second cycles over a year. These data were matched to archival data on surgery characteristics. Because surgeries inherently vary in length, we developed a new procedure to normalize surgery times to run cross-surgery comparisons. Based on this procedure, dBA values were adjusted to each normalized time point. Noise-level patterns are presented for surgeries contingent on important surgery characteristics: 16 different surgery types, operation method, day/night time point and operation complexity (complexity levels 1-3). This serves to cover a wide spectrum of day-to-day surgeries. The noise patterns reveal significant sound level differences of about 1 dBA, with the most-common noise level being spread between 55 and 60 dBA. This indicates a sound situation in many of the surgeries studied likely to cause stress in patients and staff. Absolute and relative risks of meeting or exceeding 60 dBA differ considerably across operation types. In conclusion, the study reveals that maximum noise levels of 55 dBA are frequently exceeded during visceral surgical procedures. Especially complex surgeries show, on average, a higher noise exposure. Our findings warrant active noise management for visceral surgery to reduce potential negative impacts of noise on surgical performance and outcome.
Background
A novel subcutaneous allergen immunotherapy formulation (gpASIT+™) containing Lolium perenne peptides (LPP) and having a short up‐dosing phase has been developed to treat grass ...pollen–induced seasonal allergic rhinoconjunctivitis. We investigated peptide immunotherapy containing the hydrolysate from perennial ryegrass allergens for the optimum dose in terms of clinical efficacy, immunogenicity and safety.
Methods
This prospective, double‐blind, placebo‐controlled, phase IIb, parallel, four‐arm, dose‐finding study randomized 198 grass pollen–allergic adults to receive placebo or cumulative doses of 70, 170 or 370 μg LPP. All patients received weekly subcutaneous injections, with the active treatment groups reaching assigned doses within 2, 3 and 4 weeks, respectively. Efficacy was assessed by comparing conjunctival provocation test (CPT) reactions at baseline, after 4 weeks and after completion. Grass pollen–specific immunoglobulins were analysed before and after treatment.
Results
Conjunctival provocation test (CPT) response thresholds improved from baseline to V7 by at least one concentration step in 51.2% (170 μg; P = .023), 46.3% (370 μg), and 38.6% (70 μg) of patients receiving LPP vs 25.6% of patients receiving placebo (modified per‐protocol set). Also, 39% of patients in the 170‐μg group became nonreactive to CPT vs 18% in the placebo group. Facilitated allergen‐binding assays revealed a highly significant (P < .001) dose‐dependent reduction in IgE allergen binding across all treatment groups (70 μg: 17.1%; 170 μg: 18.8%; 370 μg: 26.4%). Specific IgG4 levels increased to 1.6‐fold (70 μg), 3.1‐fold (170 μg) and 3.9‐fold (370 μg) (mPP).
Conclusion
Three‐week immunotherapy with 170 μg LPP reduced CPT reactivity significantly and increased protective specific antibodies.
Patients with allergic rhinoconjunctivitis are susceptible to both nasal and ocular symptoms. The conjunctival provocation test (CPT) is an established diagnostic procedure used in allergic ...rhinoconjunctivitis, particularly to document a patient's current reactivity to allergens. To date, there are no international guidelines defining the CPT. No approved evaluation method exists for interpreting CPT results. This paper aims to establish the digital analysis of macroimages as an objective, validated and standardized method for interpreting CPT results.
In a clinical immunotherapy trial with 155 patients, treatment progress was documented based on the CPT. Local investigators used a symptom score to grade tearing, reddening and the patients' subjective perception of symptoms (mucosal irritation). A central observer rated conjunctival hyperemia via digital photography. Digital image analysis software was utilized to determine conjunctival hyperemia.
Spearman's correlation between the local investigators' and the central observer's ratings was r = 0.729 (p < 0.001); the percentage of total agreement was 48% (based on 739 photos). Digital image analysis (based on 48 photos) had a high percentage of total agreement with the central observer's ratings (69%) but a low percentage of total agreement with the investigators' ratings (38%). The corresponding correlations were r = 0.264 and 0.064, respectively.
Photography-based rating by a central observer may represent a valuable supplement to the local investigator's assessment for making an objective evaluation of CPT results. Digital image analysis possesses the potential of being an objective evaluation method compared to the wide-spread subjective evaluation by the investigators.
The H1 very forward proton spectrometer at HERA Astvatsatourov, A.; Cerny, K.; Delvax, J. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
02/2014, Letnik:
736
Journal Article
Recenzirano
The very forward proton spectrometer, VFPS, is a component of the H1 detector at the HERA collider. Scattered protons emitted with a polar angle less than 1mrad and carrying a fractional energy 1−xP, ...0.008<xP≤0.028 of the incident proton beam energy can be detected by scintillating fiber detectors which are read out by position sensitive photo-multipliers. These detectors are contained in Roman pot stations which are moved close to the circulating proton beam. The structure, operation and performance of the two Roman pot stations located at about 220m from the H1 interaction point in the cryogenic section of the proton ring are described.
The conjunctival provocation test (CPT) is a diagnostic procedure for the assessment of allergic diseases. Photographs are taken before and after provocation increasing the redness of the conjunctiva ...due to hyperemia.
We propose and evaluate an automatic image processing pipeline for objective and quantitative CPT.
After scale normalization based on intrinsic image features, the conjunctiva region of interest (ROI) is segmented combining thresholding, edge detection and Hough transform. Redness of the ROI is measured from 0 to 1 by the average pixel redness, which is defined by truncated projection in HSV space. In total, 92 images from an observational diagnostic study are processed for evaluation. The database contains images from two visits for assessment of the test-retest reliability (46 images per visit).
All images were successfully processed by the algorithm. The relative redness increment correlates between the two visits with Pearson's r = 0.672 (p < .001). Linear correlation of the automatic measure is larger than the manual measure (r = 0.59). This indicates a higher reproducibility and stability of the automatic method.
We presented a robust and effective way to objectify CPT. The algorithm operates on low resolution, is fast and requires no manual input. Quantitative CPT measures can now be established as surrogate endpoint in controlled clinical trials.
We discuss the non-linear sigma model representing a NSR open string in a curved background with non-zero
B
μν
-field. With this coupling the theory is not automatically supersymmetric, due to ...boundary contributions. When
B=0 supersymmetry is ensured by the conditions that follow as the boundary contribution to the field equations. We show that inclusion of a particular boundary term restores this state of affairs also in the presence of a
B-field. The boundary conditions derived from the field equations in this case agree with those that have been proposed for constant
B-field. A coupling to a boundary
A
μ
-field will modify both the boundary conditions and affect the supersymmetry. It is shown that there is an
A-coupling with non-standard fermionic part that respects both the supersymmetry and the shift symmetry (in the
B and
A fields), modulo the (modified) boundary conditions.
Inclusive D* production is measured in deep-inelastic ep scattering at HERA with the H1 detector. In addition, the production of dijets in events with a D* meson is investigated. The analysis covers ...values of photon virtuality 2< Q^2 <=100 GeV^2 and of inelasticity 0.05<= y <= 0.7. Differential cross sections are measured as a function of Q^2 and x and of various D* meson and jet observables. Within the experimental and theoretical uncertainties all measured cross sections are found to be adequately described by next-to-leading order (NLO) QCD calculations, based on the photon-gluon fusion process and DGLAP evolution, without the need for an additional resolved component of the photon beyond what is included at NLO. A reasonable description of the data is also achieved by a prediction based on the CCFM evolution of partons involving the k_T-unintegrated gluon distribution of the proton.
Inclusive D*± production is measured in deep-inelastic ep scattering at HERA with the H1 detector. In addition, the production of dijets in events with a D*± meson is investigated. The analysis ...covers values of photon virtuality 2 ≤ Q2 ≤ 100 GeV2 and of inelasticity 0.05 ≤ y ≤ 0.7. Differential cross sections are measured as a function of Q2 and x and of various D*± meson and jet observables. Within the experimental and theoretical uncertainties all measured cross sections are found to be adequately described by next-to-leading order (NLO) QCD calculations, based on the photon-gluon fusion process and DGLAP evolution, without the need for an additional resolved component of the photon beyond what is included at NLO. A reasonable description of the data is also achieved by a prediction based on the CCFM evolution of partons involving the kT-unintegrated gluon distribution of the proton.
PDF
