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In this article, we apply methods of fixed point theory to investigate a Lambda policy iteration with a randomization algorithm for mappings that are merely weak contractions. As simple examples show, this class of mappings provide a much wider scope than the one afforded by strong contractions usually considered in the literature. More specifically, we investigate the properties of reinforcement learning procedures which have been developed for feedback control, in the framework of fixed point theory. Under fairly general assumptions, we determine sufficient conditions for the convergence with probability one in infinite dimensional policy spaces. [ABSTRACT FROM AUTHOR]

The measurements of acoustic waves created by a quake are of great interest for planets with hot and dense atmospheres, like Venus, because surface deployments of seismometers will last only a few hours, whereas freeflying balloons could fly many days. Infrasound sensors can also be used to constrain subsurface properties during active seismic experiments. This study presents a controlled source seismo-acoustic experiment using infrasonic sensors and accelerometers mounted on a tethered helium balloon. Both the acoustic waves generated below the balloon by seismic surface waves, and the ones generated by strong ground motions above the seismic source are clearly observed and separated on the records of the various instruments. This data set allows various validations and investigations. First, it validates the ground to air coupling theory and our numerical modelling tools. Then, it allows us to demonstrate that antenna processing of infrasound sensors deployed below the balloon can estimate the arrival incidence angle of the acoustic waves within 10°. Finally, a polarization analysis of the accelerometers taped on the balloon envelope is presented. It demonstrates that accelerometer records are strongly dependent on their location on the balloon due to its deformations and rotations. However, the different acoustic signals can be distinguished through their polarization, and a best sensor location is estimated at the bottom of the balloon envelope. These results are a first step towards detecting and locating seismic activity using airborne acoustic sensors on Venus and elsewhere. However, some observations of earthquake signals in a more realistic geometry are still missing. [ABSTRACT FROM AUTHOR]

Local seismic networks are usually designed so that earthquakes are located inside them (primary azimuthal gap <<180°) and close to the seismic stations (0-100 km). With these local or near-regional networks (0°-5°), many seismological observatories still routinely locate earthquakes using 1-D velocity models. Moving towards 3-D location algorithms requires robust 3-D velocity models. This work takes advantage of seismic monitoring spanning more than 30 yr in the Pyrenean region. We investigate the influence of a well-designed 3-D model with station corrections including basins structure and the geometry of the Mohorovicic discontinuity on earthquake locations. In the most favourable cases (GAP < 180° and distance to the first station lower than 15 km), results using 1-D velocity models are very similar to 3-D results. The horizontal accuracy in the 1-D case can be higher than in the 3-D case if lateral variations in the structure are not properly resolved. Depth is systematically better resolved in the 3-D model even on the boundaries of the seismic network (GAP > 180° and distance to the first station higher than 15 km). Errors on velocity models and accuracy of absolute earthquake locations are assessed based on a reference data set made of active seismic, quarry blasts and passive temporary experiments. Solutions and uncertainties are estimated using the probabilistic approach of the NonLinLoc (NLLoc) software based on Equal Differential Time. Some updates have been added to NLLoc to better focus on the final solution (outlier exclusion, multiscale grid search, S-phases weighting). Errors in the probabilistic approach are defined to take into account errors on velocity models and on arrival times. The seismicity in the final 3-D catalogue is located with a horizontal uncertainty of about 2.0 ± 1.9 km and a vertical uncertainty of about 3.0 ± 2.0 km. [ABSTRACT FROM AUTHOR]

Using a variational method introduced in [D. Azé and J.-N. Corvellec, 'A variational method in fixed point results with inwardness conditions', Proc. Amer. Math. Soc. 134(12) (2006), 3577-3583], deriving directly from the Ekeland principle, we give a general result on the existence of a fixed point for a very general class of multifunctions, generalizing the recent results of [Y. Feng and S. Liu, 'Fixed point theorems for multi-valued contractive mappings and multi-valued Caristi type mappings', J. Math. Anal. Appl. 317(1) (2006), 103-112; D. Klim and D. Wardowski, 'Fixed point theorems for set-valued contractions in complete metric spaces', J. Math. Anal. Appl. 334(1) (2007), 132-139]. Moreover, we give a sharp estimate for the distance to the fixed-points set. [ABSTRACT FROM AUTHOR]

Background: Drug hypersensitivity reactions are common and can be life-threatening. Confirmation of the diagnosis should be rigorous and based on clinical history and a physical examination, possibly followed by skin tests and drug provocation tests.Objective: To describe the outcome of drug provocation tests in evaluating patients with histories suggesting drug allergy.Design: Retrospective analysis of clinic case series.Setting: The department for drug allergy at a university hospital.Patients: 898 consecutive patients with suspected immediate drug allergy referred to the clinic between September 1996 and August 2001. Patients with severe skin reactions and those with positive results on skin tests for beta-lactams were excluded.Intervention: Single-blinded administration of increasing doses of the suspected drug, up to the usual daily dose, under strict hospital surveillance.Results: 1372 drug provocation tests were performed using various drugs, including beta-lactams (30.3%), aspirin (14.5%), other nonsteroidal anti-inflammatory drugs (11.7%), paracetamol (8.9%), macrolides (7.4%), and quinolones (2.4%). There were 241 (17.6%) positive drug provocation test results. Drug provocation reproduced the same symptoms, albeit milder and of a shorter duration, in the following patients: 13 (5.4%) with a history of anaphylactic shock, 17 (7.0%) with a history of anaphylaxis without shock, 10 (4.1%) with a history of laryngeal edema, 19 (7.9%) with a history of bronchospasm, 160 (66.4%) with a history of urticaria, and 22 (9.1%) with a history of maculopapular eruption. All adverse reactions were completely reversed by prednisolone, H(1)-antihistamines, and epinephrine as needed.Limitations: Falsely negative results on drug provocation tests may have occurred because of loss of sensitization, rare cofactors not included in the diagnostic procedure, and tolerance induction during provocation.Conclusions: Drug provocation tests in individuals with suspected drug allergy performed in carefully controlled settings can confirm drug hypersensitivity. [ABSTRACT FROM AUTHOR]

Describes a case of a patient with skin reactions to some antihistamines, as demonstrated by oral challenges. Symptoms; Diagnosis; Treatment.

Objective: Focal cooling is emerging as a relevant therapy for drug-resistant epilepsy (DRE). However, we lack data on its effectiveness in controlling seizures that originate in deep-seated areas like the hippocampus. We present a thermoelectric solution for focal brain cooling that specifically targets these brain structures., Methods: A prototype implantable device was developed, including temperature sensors and a cannula for penicillin injection to create an epileptogenic zone (EZ) near the cooling tip in a non-human primate model of epilepsy. The mesial temporal lobe was targeted with repeated penicillin injections into the hippocampus. Signals were recorded from an sEEG (Stereoelectroencephalography) lead placed 2 mm from the EZ. Once the number of seizures had stabilized, focal cooling was applied, and temperature and electroclinical events were monitored using a customized detection algorithm. Tests were performed on two Macaca fascicularis monkeys at three temperatures., Results: Hippocampal seizures were observed 40-120 min post-injection, their duration and frequency stabilized at around 120 min. Compared to the control condition, a reduction in the number of hippocampal seizures was observed with cooling to 21°C (Control: 4.34 seizures, SD 1.704 per 20 min vs Cooling to 21°C: 1.38 seizures, SD 1.004 per 20 min). The effect was more pronounced with cooling to 17°C, resulting in an almost 80% reduction in seizure frequency. Seizure duration and number of interictal discharges were unchanged following focal cooling. After several months of repeated penicillin injections, hippocampal sclerosis was observed, similar to that recorded in humans. In addition, seizures were identified by detecting temperature variations of 0.3°C in the EZ correlated with the start of the seizures., Significance: In epilepsy therapy, the ultimate aim is total seizure control with minimal side effects. Focal cooling of the EZ could offer an alternative to surgery and to existing neuromodulation devices., (© 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

This study investigated the effect of reducing dietary crude protein (CP) content in the grower and finisher diets of broiler chickens on breast meat quality, muscle protein functionality, growth, carcass yield, and meat yield. To achieve this, a total of 1,269 one-day-old male Ross 308 chicks were fed 1 of 3 diets replicated 9 times each in a randomized complete block design with 9 blocks. The diets included a control (20.4% and 19.5% CP in the grower and finisher phase, respectively), a diet with a 1.5% reduction (CP-1.5%) and a diet with a 3.0% reduction (CP-3.0%) in CP content in both the grower and finisher phases. At the end of the experiment, the reduced-CP diets had no impact on body weight, feed intake, or feed conversion ratio. However, reduced-CP diet resulted in reduced (P < 0.001) total nitrogen intake (-7.46 and -11.94% in CP-1.5% and CP-3.0%, respectively). Breast meat quality was assessed (n = 36 birds/group), and the experimental diets were associated with a slightly increased (P = 0.07) ultimate pH (5.75, 5.79, and 5.81 for the control, CP-1.5%, and CP-3.0%, respectively). Breast fillets from the CP-1.5% and CP-3.0% groups had lower yellowness (b*, P < 0.001) and lower cooking loss (CL, P < 0.001) values than the control. Moreover, the solubility, emulsion activity, and stability indices of the sarcoplasmic and myofibrillar fractions of muscle proteins were not influenced by the diets. CP-1.5% and CP-3.0% diets were associated with an increased (P < 0.001) breast yield (18.39, 19.21, and 19.61% for the control, CP-1.5%, and CP-3.0%, respectively) while leg yield remained unchanged. Additionally, breast meat nutritional properties including protein and lipid contents were not impacted by the experimental diets. In conclusion, the CP content in the grower and finisher diets of broiler chickens can be reduced by as much as 3.0% without detrimental effects on performance or on meat quality as long as birds' amino acid requirements are adequately met., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: In Tunisia, the management of Adult Hodgkin's Lymphoma (HL) has been standardized since 1999. We propose in this study to report the therapeutic results of the national protocol of adult HL treatment (MDH2008)., Patients and Methods: Our study is prospective multicenter interesting 444 patients followed for HL between July 2008 and June 2013 and treated according to the MDH2008 protocol. The median age of our patients was 30 years. B symptoms were present in 62.8 % of our patients. According to the Ann Arbor classification, our patients were in stages I, II, III and IV in 3 %, 42 %, 26 % and 29 %, respectively. The MDH2008 protocol is based on a strategy adapted to the therapeutic response to 2 cycles of chemotherapy., Results: Response≥75 % to 2 courses of chemotherapy was achieved in 43 % of patients and the response rate at the end of treatment was 92.1 %. Forty-eight patients (11.4 %) had primary failure. In the multi-variant study, bulky mediastinal mass (IMT≥0.35) was an independent predictive factor of primary failure (P: 0.000). Nineteen toxic deaths (4.35 %) were reported. The relapse rate was 7.8 %. Event free survival, relapse-free survival and overall survival at 5years were 75 %, 89 % and 90 %, respectively. Adaptation of the treatment to the 2 cycles response was effective in unfavorable early stages and advanced stages., Conclusion: Compared to MDH2002 (second version of Tunisian prospective protocol), the MDH2008 reduced the primary failure rate, the rate of toxic deaths with escalated BEACOPP and the rate of relapse in Tunisian patients., (Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: A firm diagnosis of drug hypersensitivity, because it may re-induce the reaction, is seldom confirmed. Causality assessment algorithms are therefore of interest., Aims: The objective of this work was to compare three algorithms in the diagnosis of drug hypersensitivity., Methods: Evaluation of 120 clinical histories of drug hypersensitivity was carried out: 60 involving beta-lactams (50%) and 60 involving non-steroidal anti-inflammatory drugs (50%). Each of these groups of patients underwent a standardised allergy diagnosis, which included a detailed anamnesis, skin tests and, often, provocation tests under strict hospital surveillance. Unaware of the final allergy diagnosis, scores were established for all of the cases and compared using algorithms suggested by Begaud and coworkers [2, 20], Jones [13] and Naranjo et al. [21]., Results: Although the methods of Jones [13] and Naranjo et al. [21] were perfectly concordant (k=1), no concordance was noted using the Begaud and coworkers [2, 20] method., Conclusions: All three algorithms are dissimilar regarding the diagnosis of drug hypersensitivity.

Background: This study was performed to evaluate the diagnostic accuracy of a pharmacovigilance algorithm in patients with 1 or more histories suggestive of drug hypersensitivity., Methods: We performed a retrospective analysis of a clinic case series. We analyzed patients with suspected clinical reactions of drug hypersensitivity. Patients with severe skin reactions were excluded. Patients with history of drug allergy were subjected to additional testing to validate this history. Following a detailed clinical history, skin tests were performed. If skin tests were not available or validated, drug provocation tests were conducted. Assessment of causality was established by an investigator unaware of drug testing results using a pharmacovigilance algorithm that was then compared with the final diagnosis., Results: A total of 677 consecutive patients with 1001 reactions were analyzed. No score could be given because of the absence of 1 of the criteria required for 204 reactions (20.4%). For 720 reactions (71.9%), a dubious causality assessment score was given. Drug hypersensitivity was confirmed by drug testing in 175 reactions (17.5%) and eliminated in 826 reactions (82.5%). Sensitivity of the algorithm was 10.3% and specificity was 76.9%. Although there were 1.7% false-positive scores, there were no false-negative scores. The logistic regression that was performed to look for independent clinical risk factors linked to the drug hypersensitivity diagnosis found 3 parameters: likely causality assessment score, drug reintroduction in clinical history, and delay between reaction and last drug intake of less than 1 hour., Conclusion: A pharmacovigilance algorithm is not accurate for the diagnosis of drug hypersensitivity reactions and cannot replace drug allergy testing.

MACROLIDE CLASSES: Macrolides are characterized by their basic structure made up of a lactonic cycle with 2 osidic chains. They are classified according to the number of carbon atoms in the cycle: 14-membered macrolides (erythromycin, troleandomycin, roxithromycin, dirithromycin, clarithromycin), 15-membered macrolides (azithromycin) and 16-membered macrolides (spiramycin, josamycin, midecamycin). MACROLIDE ALLERGY: Allergy to macrolides is extremely rare (0.4% to 3% of treatments). The little information available in the literature is insufficient to establish the usefulness of diagnostic tests. An immediate IgE-dependent hypersensitivity has been shown with erythromycin in some cases but the mechanism remains unknown and skin tests are quite often negative. Clinical manifestations are the same as those encountered with beta-lactams. It would appear that macrolide allergies are unlikely to be class allergies. This is important as eviction advice could be limited to the single causal macrolide.

Objective: Allergic drug reactions to macrolides are extremely rare and there is little information in the literature concerning relevant diagnostic tests., Patients and Methods: Twenty-one patients were recently seen for assumed allergies (principally urticaria) to diverse macrolides. Skin tests (prick and intradermal tests) were performed with injectable forms of spiramycin and erythromycin. Seventeen out of 21 patients were provoked under strict hospital surveillance., Results: Only 3 patients had a positive provocation test and were thus truly allergic (to spiromycin). They had positive skin tests to both macrolides tested., Conclusion: Most hypersensitivity reactions to macrolides are therefore diagnosed with provocation tests.

Allergic and pseudoallergic reactions frequently occur in hospitalized patients and represent up to one-third of adverse drug reactions. Allergic reactions are unpredictable reactions, related to immunologic mechanisms. Pseudoallergic reactions mimic allergic reactions but no drug-specific antibody or T-cell proliferation can be demonstrated. Clinical presentations are numerous and heterogeneous, from a mild urticaria to a dramatic anaphylactic shock and an extensive bullous skin disease. A true diagnosis is rarely set up and the tools for it are lacking. In this review, we will focus on some epidemiological data concerning these reactions, including data on incidence, mortality and cost.

Chronic administration of N(G)-nitro-L-arginine methyl ester (L-NAME) to rats induces systemic hypertension and progressive development of preglomerular sudanophilic (SB+) lesions. This study investigates whether progression of SB+ lesion formation froin 4 to 6 wk of L-NAME treatment (20 mg/kg per d, orally) would be affected by 2 wk administration of either the angiotensin II type 1 receptor antagonist candesartan cilexetil (3 and 10 mg/kg per d) or the vasodilator hydralazine (15 mg/kg per d). Frequencies of arcuate arterial branches (ArcB), interlobular arteries (ILA), and afferent arterioles (AA) endowed with SB+ lesions were assessed on preglomerular vasculatures isolated after HCl maceration. Systolic BP (SBP, tail-cuff manometry) increased from a baseline of 125+/-2 to 185+/-4, and to 193+/-4 mmHg after 4 and 6 wk of L-NAME treatment, respectively. During the fourth- to sixth-week period, albumin excretion increased significantly from 3.7+/-1.1 to 52.5+/-22.4 mg/24 h. At that time, SB+ lesions affected 62+/-8, 61+/-8, and 13+/-4% of ArcB, ILA, and AA, respectively. Candesartan cilexetil dose dependently reduced SBP, albumin excretion, and lesion development. At the highest dose, SB+ lesions only affected 12+/-6, 15+/-7, and 1+/-1% of ArcB, ILA, and AA, respectively. Hydralazine similarly reduced SBP and albumin excretion, although frequencies of SB+ lesions appeared less affected along ArcB and ILA. In conclusion, progression of preglomerular SB+ lesion formation during L-NAME hypertension can be prevented by angiotensin II type 1 receptor blockade, partly through pressure-lowering effects.