development of tolerance
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Author(s):  
Martin Roth ◽  
Paul Schaechtl ◽  
Andreas Giesert ◽  
Benjamin Schleich ◽  
Sandro Wartzack

AbstractTolerance allocation methods significantly contribute to the qualification of Additive Manufacturing (AM) for (small-)series production ensuring high performance and efficiency. However, their usage prerequisites the availability of quantitative, reliable information on the impact of the assigned tolerances on the resulting manufacturing costs. The given article proposes a novel methodology for the systematic development of tolerance-cost curves for a cost-efficient tolerancing of 3D-printed parts. The proposed structured workflow aims at serving as a general guideline for both researchers and practitioners, while the exemplarily chosen perspective from Fused Layer Modeling (FLM) illustrates its adaption to a specific AM technology. The indirect, non-apparent interrelations between tolerances and resulting costs are modelled with the aid of an activity-based cost model, whereas the individual costs elements are mapped as function of the values for the machine-specific process parameters for AM, e.g., layer height or printing speed, which are required to achieve the assigned design tolerances. The total procedure covers all relevant steps, viz. the identification and quantification of the single cost items, the design of benchmark artifacts, adapted to given manufacturing and measuring techniques, the empirical determination of data on cost and geometrical accuracy by design of experiments and tolerance-cost curves. Its exemplary application to an academic use case shows its general applicability and benefits, but also its current limitations.


2021 ◽  
Vol 11 (12) ◽  
pp. 1354
Author(s):  
Héctor Isaac Rocha-González ◽  
Lidia Elizabeth De la Cruz-Álvarez ◽  
Ashuin Kammar-García ◽  
Samuel Canizales-Quinteros ◽  
Juan Carlos Huerta-Cruz ◽  
...  

The efficacy of anti-obesity drugs usually does not consider the high degree of interindividual variability in responses to the drug which could affect the decision to withdraw the drug early due to ineffectiveness or to continue therapy according to specific expectations of success. The aim of this study was to analyze body weight loss in kilograms during the first month (1 mo-BWLkg) of treatment with 30 mg phentermine and development of tolerance to phentermine, on its 6-month efficacy. One hundred sixty-six subjects with obesity were individually or jointly analyzed in the study. Subjects with 1 mo-BWLkg of <1 kg, 1–3 kg, 3–5 kg, and ≥5 kg reached 6-month mean percentage body weight reductions (BWR%) of approximately 3%, 5%, 10%, and 15%, respectively. Development of late tolerance (4–6 months) to phentermine had a lower impact than early tolerance (2–3 months). Subjects with 1 mo-BWLkg <3 kg who developed early tolerance did not achieve relevant BWR% (≥5%) at month 6, while the rest of the subgroups achieved increasing and progressive BWR%, according to their 1 mo-BWLkg range and time of onset of tolerance. The 1 mo-BWLkg and development of tolerance to phentermine could be useful to predict the expected 6-month efficacy trends in obese patients treated with 30 mg phentermine.


2021 ◽  
Vol 12 ◽  
Author(s):  
Anum Muzaffar ◽  
Sami Ullah ◽  
Fazal Subhan ◽  
Zahid Nazar ◽  
Syed Mehdi Hussain ◽  
...  

Cannabis abuse is a common public health issue and may lead to considerable adverse effects. Along with other effects, the dependence on cannabis consumption is a serious problem which has significant consequences on biochemical and clinical symptoms. This study intends to evaluate the harmful effects of the use of cannabis on thyroid hormonal levels, cardiovascular indicators, and psychotic symptoms in the included patients. This prospective multicenter study was conducted on cannabis-dependent patients with psychotic symptoms (n = 40) vs. healthy control subjects (n = 40). All participants were evaluated for psychiatric, biochemical, and cardiovascular physiological effects. Patients were selected through Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria and urine samples, exclusively for the evaluation of cannabis presence. Serum thyroid stimulating hormone (TSH), T3, and T4 levels were measured using the immunoassay technique. Patients were assessed for severity of depressive, schizophrenic, and manic symptoms using international ranking scales. Various quantifiable factors were also measured for the development of tolerance by cannabis. Among the patients of cannabis abuse, 47.5% were found with schizophrenia, 20% with schizoaffective symptoms, 10% with manic symptoms, and 22.5% with both manic and psychotic symptoms. In the group–group and within-group statistical analysis, the results of thyroid hormones and cardiovascular parameters were non-significant. The psychiatric assessment has shown highly significant (p &lt; 0.001) difference of positive, negative, general psychopathology, and total scores [through Positive and Negative Syndrome Scale (PANSS) rating scales] in patients vs. the healthy control subjects. The study revealed that cannabis abuse did not significantly alter thyroid hormones and cardiovascular parameters due to the development of tolerance. However, the cannabis abuse might have a significant contributing role in the positive, negative, and manic symptoms in different psychiatric disorders.


Author(s):  
Steven Kinsey ◽  
Olivia Vanegas ◽  
Kristen Trexler ◽  
Floyd Steele ◽  
Matthew Eckard

The stress response evolved as a series of neural and endocrine mechanisms that protect the host organism from threats to homeostasis. Repeated use of psychotropic drugs can lead to the development of tolerance (i.e., decreased drug activity at a given dose) and drug dependence, as indicated by withdrawal syndromes following drug abstinence. Drug withdrawal is often overtly stressful, although acute drug exposure may also represent a threat to homeostasis. This article explores the neuroendocrine effects of drugs of abuse and some of the ways in which stress and appetitive mechanisms interact.


2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Abigail Lang ◽  
Shrey Patel ◽  
Karen Rychlik ◽  
Deanna Caruso ◽  
Xiaobin Wang ◽  
...  

Abstract Background Knowledge is limited about the relationship between clinical reactivity to foods through breastfeeding and long-term food allergy outcomes. We explored parent-perceived symptoms of food allergy via breastfeeding and the association with future tolerance. Methods Subjects identified from the Chicago Food Allergy Study (2005–2011) were categorized by parent-reported reactions to maternally ingested foods via breastfeeding (50/898 peanut-allergic, 69/620 egg-allergic, and 153/589 milk-allergic). The primary outcome was tolerance [passed oral food challenge (OFC) or consumption of previously implicated food]. Secondary outcomes included severe reactions (anaphylaxis and/or cardiovascular/respiratory symptoms) and additional concomitant food allergies. Univariate chi-square analyses were performed to assess for association between variables, followed by logistic regression models. Results Of the 50 subjects with parent-reported peanut-associated symptoms with breastfeeding, none gained tolerance. There were no significant associations between parent-reported breastfeeding symptoms and development of tolerance for egg and milk (egg: OR 0.46, 95% CI 0.21–1.01, p = 0.053; milk: OR 1.13, 95% CI 0.70–1.81, p = 0.614). All egg-allergic subjects with parent-perceived symptoms while breastfeeding also reported multiple food allergies (n = 69), but milk- and peanut-allergic subjects were not more likely to have multiple allergies (milk: OR 1.89, 95% CI 0.88–4.02, p = 0.10; peanut: OR 2.36, 95% CI 0.72–7.76, p = 0.16). There were no significant associations between parent-reported breastfeeding symptoms and subsequent reaction severity. Conclusions A significant proportion of parents perceive symptoms of food allergy attributable to indirect breastfeeding exposures. Our exploratory analysis suggests that infants with parent-perceived clinical reactivity to peanut via breastmilk may be less likely to gain tolerance. Infants with parent-reported reactivity to egg via breastmilk exposure were more likely to report multiple food allergies. Further rigorous prospective studies are needed to clarify the true prevalence of IgE-mediated food allergy symptoms attributable to indirect breastfeeding exposures and the association with development of tolerance.


2021 ◽  
Author(s):  
Mauro Congiu ◽  
Laura Micheli ◽  
Michele Santoni ◽  
Claudia Sagheddu ◽  
Anna Lisa Muntoni ◽  
...  

AbstractOpioids are essential drugs for pain management, although long-term use is accompanied by tolerance, necessitating dose escalation, and dependence. Pharmacological treatments that enhance opioid analgesic effects and/or attenuate the development of tolerance (with a desirable opioid-sparing effect in treating pain) are actively sought. Among them, N-palmitoylethanolamide (PEA), an endogenous lipid neuromodulator with anti-inflammatory and neuroprotective properties, was shown to exert anti-hyperalgesic effects and to delay the emergence of morphine tolerance. A selective augmentation in endogenous PEA levels can be achieved by inhibiting N-acylethanolamine acid amidase (NAAA), one of its primary hydrolyzing enzymes. This study aimed to test the hypothesis that NAAA inhibition, with the novel brain permeable NAAA inhibitor AM11095, modulates morphine’s antinociceptive effects and attenuates the development of morphine tolerance in rats. We tested this hypothesis by measuring the pain threshold to noxious mechanical stimuli and, as a neural correlate, we conducted in vivo electrophysiological recordings from pain-sensitive locus coeruleus (LC) noradrenergic neurons in anesthetized rats. AM11095 dose-dependently (3–30 mg/kg) enhanced the antinociceptive effects of morphine and delayed the development of tolerance to chronic morphine in behaving rats. Consistently, AM11095 enhanced morphine-induced attenuation of the response of LC neurons to foot-shocks and prevented the attenuation of morphine effects following chronic treatment. Behavioral and electrophysiological effects of AM11095 on chronic morphine were paralleled by a decrease in glial activation in the spinal cord, an index of opioid-induced neuroinflammation. NAAA inhibition might represent a potential novel therapeutic approach to increase the analgesic effects of opioids and delay the development of tolerance.


Author(s):  
Sam Craft ◽  
Jason A. Ferris ◽  
Monica J. Barratt ◽  
Larissa J. Maier ◽  
Michael T. Lynskey ◽  
...  

AbstractSynthetic cannabinoid receptor agonists (SCRAs) may be used as an alternative to natural cannabis; however, they may carry a greater risk of problematic use and withdrawal. This study aimed to characterise the withdrawal symptom profile of SCRAs and compare their profile of effect with high-potency herbal cannabis. Global Drug Survey data (2015 and 2016) were used to access a clinically relevant sample of people reporting use of SCRAs >10 times in the past 12-months, a previous SCRA quit attempt, and lifetime use of high-potency herbal cannabis. Participants completed an 11-item SCRA withdrawal symptom checklist and compared SCRAs and high-potency herbal cannabis on their onset and duration of effects, speed of the development of tolerance, severity of withdrawal, and difficulty with dose titration. Participants (n = 284) reported experiencing a mean of 4.4 (95% CI: 4.1, 4.8) withdrawal symptoms after not using SCRAs for >1 day; most frequently reported were sleep issues (59.2%), irritability (55.6%), and low mood (54.2%). Withdrawal symptoms were significantly associated with frequency (>51 vs. 11–50 times per year: IRR = 1.43, 95% CI: 1.16, 1.77, p = 0.005) and quantity (grams per session: IRR = 1.13, 95% CI: 1.05, 1.22, p = 0.001) of SCRA use. Compared to high-potency herbal cannabis, SCRAs were rated as having a faster onset and shorter duration of effects, faster development of tolerance, and more severe withdrawal (p’s < 0.001). In conclusion, SCRA withdrawal symptoms are more likely to occur after greater SCRA exposure. The effects of SCRA indicate a more severe withdrawal syndrome and a greater risk of problematic use than natural cannabis.


2021 ◽  
Vol 49 (5) ◽  
pp. 25-27
Author(s):  
Mitsuhiro Okamoto ◽  
Satoru Takafuji ◽  
Shintaro Inoue ◽  
Yuya Tanaka

Fish allergy is generally thought to be persistent, and approximately 80% of patients with fish allergies do not develop tolerance even 10 years after diagnosis. There have been no reports of rapid tolerance development in patients with severe fish allergies. We report the development of tolerance 16 months after the diagnosis of fish allergies. A 13-month-old boywas diagnosed with rosefish allergy (Sebastes matsubarae) and Japanese jack mackerel allergy (Trachurus japonicus). To find out which species of fish he could consume safely, he underwentseveral oral food challenge (OFC) tests. It was determined that he could consume tuna, salmon, cod, sardine, chub mackerel (Scomber japonicus), and Japanese amberjack (Seriola quinqueradiata) without eliciting signs of allergy. He continued to eat the fish that did not produce allergic reactions three to four times a week. The titer of serum allergen-specific immunoglobulin E (IgE) to fish had decreased in a subsequent ImmunoCAP®-specific IgE bloodtest performed 16 months after the diagnosis of the rosefish allergy. Following this test result, he underwent OFCs with rosefish and Japanese jack mackerel, both of which turned out to be negative, and it was determined that he had developed tolerance to fish. In this case, the repeated OFCs were useful in identifying fish species that were safe for consumption. In addition, the decrease in allergen-specific IgE was useful in predicting the development of tolerance. We hypothesize that proactive consumption of available fish species may lead to this rapid induction of tolerance to fish allergens


Author(s):  
Alla K. Belousova ◽  
Alena V. Samarskaya ◽  
Ekaterina V. Kryazhkova

The paper presents the results of a study of tolerance relation to uncertainty and creativity among senior schoolchildren with a critical style of thinking. The authors use valid diagnostic methods: A. Belousovas thinking style questionnaire, S. Badners uncertainty tolerance questionnaire, and P. Torrances test. The sample consists of 90 senior schoolchildren, both boys and girls. As a result of the study, the groups of schoolchildren with a dominant critical and practical style of thinking have been identified. The authors show that there are significant differences in the development of relationships between uncertainty and creativity tolerance scales, between uncertainty tolerance and critical thinking style, creativity and critical thinking style. The differences have been obtained in the development of tolerance for uncertainty, creativity in relation to the practical style of thinking.


2021 ◽  
Vol 10 (2) ◽  
Author(s):  
Valentyna Semychenko ◽  
◽  
Oksana Oleksyuk ◽  
Kateryna Artyushina ◽  
◽  
...  

The article considers the problem of uncertainty as an integral attribute of modern human life. The importance of forming tolerance to uncertainty as an important means of organizing the life path of an individual is revealed. It is determined that the very ability of a young person to find his place in society, to properly build interpersonal relationships within the uncertainty of life events affects the future of both professional and life success. A young person in situations of uncertainty chooses one of two main strategies of action: destructive and constructive, which depends on the motivation and significance of the event for the individual. Scientists have developed different methods for studying tolerance / intolerance to uncertainty. This article presents the results of an empirical study that reveals the features of the development of tolerance for uncertainty in student youth


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