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The effectiveness of rice husk on pack carburizing process of low-carbon steel was investigated. The process was carried out at 850°C for 2, 4 and 6 hours. Carbon content of the specimen materials is 0.082%. Rice husk charcoal and rice husk powder was then compared to graphite powder. All of the media were sifted on 50 mesh sieve. After the process, all specimens were reheated up to 850°C, and then, hold it for 5 minutes. Subsequently, they were quenched into water at 28°C. The result shows that the effectiveness of rice husk charcoal is better than those of other media being used in the investigation. Six hours pack carburizing utilized, rice husk charcoal resulted in the enhancement of steel surface hardness from 122 VHN to 465 VHN and increase of the proportion of martensite structure.

The effect of BaCO3 on bakau charcoal effectiveness as a carburizer for pack carburizing process was investigated. Bakau charcoal being produced from bakau trees were sifted on 30 mesh sieve. BaCO3 was then added into the bakau charcoal sieves with composition of 0, 15, 20, 25, and 30 wt %. The pack carburizing was carried out at 850 0C for 2 hours. Low-carbon steel containing 0.156 %C was used as specimen. After being carburized, all specimens were reheated at 850 0C, hold it for 5 minutes, and subsequently quenched into water at 28 oC. The result shows that BaCO3 improves bakau charcoal effectiveness as a solid media in pack carburizing proces. By adding of 20, 25 dan 30 wt % of BaCO3, it produced the case depth of 190 mm, 250 mm dan 325 mm, respectively. Martensite structure that arises on steel surface after being quenched indicates the increase of the amount of carbon atoms.

ABSTRACT The purposes of the research are to review the application strategies of semi-research learning on the students’ understanding of the characteristics of engineering materials and to reveal the role of the students. Also, to determine whether there was any significant difference on the students’ understanding whowere taught by using semi-research learning compared to the conventional one. The research method was quasi-experimental model with parallel or equivalent group, the experimental group and the control group. Each group got pretest before and posttest after the treatment. The study was conducted in Mechanical Engineering Department, Faculty of Engineering, Yogyakarta State University from September till November 2012 among 160 students of the first semester in academic year of 2012-2013. This study was using cluster sampling method by taking one class as control group and one class for experimental group. Data analysis techniques were using descriptive analysis and T-Test. Semi-research learning for the understanding on the characteristics of engineering materials can be conducted through the students’ research assignment. The students were given chance to review based on the literature and to prove through their autonomous research. After they completed their research process, they were asked to have presentation while the lecturer role as the facilitator. Most of the students were glad with this strategy because it made them as active learner to search, explore, prove and utilize their review. This learning model demanded the students to be active, independent, serious, and able to work together, to solve problems based on facts as well as scientific evidence. Also, there was significant difference on the students’ understanding of the characteristics of engineering materials, who were taught by using semi-research compared to the conventional method with the score of mean difference of 10 from 0-70 scale. Similarly, there was a difference from the mean improvement of 10 points. Keywords: Semi-research,students’ understanding of nature of engineering materials

A systematic review of pharmacogenomic studies capturing adverse drug reactions (ADRs) related to asthma medications was undertaken, and a survey of Pharmacogenomics in Childhood Asthma (PiCA) consortia members was conducted. Studies were eligible if genetic polymorphisms were compared with suspected ADR(s) in a patient with asthma, as either a primary or secondary outcome. Five studies met the inclusion criteria. The ADRs and polymorphisms identified were change in lung function tests (rs1042713), adrenal suppression (rs591118), and decreased bone mineral density (rs6461639) and accretion (rs9896933, rs2074439). Two of these polymorphisms were replicated within the paper, but none had external replication. Priorities from PiCA consortia members (representing 15 institution in eight countries) for future studies were tachycardia (SABA/LABA), adrenal suppression/crisis and growth suppression (corticosteroids), sleep/behaviour disturbances (leukotriene receptor antagonists), and nausea and vomiting (theophylline). Future pharmacogenomic studies in asthma should collect relevant ADR data as well as markers of efficacy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background: Children with asthma may have a disease course with or without exacerbations, but the relationship between exacerbations and lung function development is poorly understood., Objective: To compare lung function trajectories from birth till adolescence in asthmatic children with and without exacerbations., Methods: Children with asthma from the Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC 2000 ) birth cohort had lung function and bronchial reactivity assessed repeatedly from 1 month to 13 years. Exacerbations were diagnosed at the COPSAC clinic defined as symptoms requiring hospitalization, oral or high-dose inhaled corticosteroid treatment. Mixed models were applied to analyze lung function trajectories., Results: Children with asthma with exacerbations (N = 50) had a trajectory of increased, fixed airway obstruction compared with children without exacerbations (N = 47): z-score difference in airway resistance (sRaw z ) (95% confidence interval [CI]): +0.34 (+0.03; +0.66), P = .03, and maximal mid-expiratory flow (MMEF z ): -0.41 (-0.69; -0.13), P = .004, but no differences in forced expiratory volume (FEV z ): -0.14 (-0.41; +0.13), P = .29, or bronchial reactivity to methacholine (PD z ): +0.08 (-0.26; +0.42), P = .65. This did not change comparing lung function trajectories before and after exacerbations: z-score difference (95% CI) sRaw z : -0.04 (-0.35; 0.27), P = .80; MMEF z : 0.01 (-0.02; 0.04), P = .55; FEV z : 0.02 (-0.02; 0.05), P = .42; and PD z : -0.01 (-0.06; 0.05), P = .88., Conclusion: Children with asthma with exacerbations compared with children with asthma without exacerbations are characterized by increased airway obstruction since infancy through childhood. The airway obstruction is a fixed trajectory without progression due to exacerbations, suggesting that exacerbations are a consequence rather than a cause of diminished airway caliber in childhood., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Rationale: There is an unmet need for sensitive lung function tests for young children to aid in the diagnosis of asthma and wheezy disorders. We hypothesized that multiple breath washout (MBW) could be a valuable tool for such a purpose. Objectives: To compare the ability of MBW lung clearance index with traditional lung function measurements to discriminate between preschool children with well-controlled asthma/persistent wheeze and healthy children. Methods: We investigated 646 children from the COPSAC 2010 (Copenhagen Prospective Studies on Asthma in Childhood 2010) mother-child cohort, who completed MBW testing with nitrogen, spirometry, and plethysmography before age 6 years. Asthma/persistent wheeze was prospectively diagnosed according to a validated symptom-based algorithm at the COPSAC clinic. Student's t tests and receiver operating characteristic curves were applied to analyze the discriminative ability of the lung function indices. Results: A total of 144 (22.3%) children were diagnosed with asthma/persistent wheeze during their first 6 years of life. Lung clearance index from MBW was not significantly different in children with versus those without asthma/persistent wheeze (mean standard deviation [SD] = 6.96 [1.14] vs. 6.95 [0.93], mean difference [95% confidence interval] = 0.02 [-0.18 to 0.22], P  = 0.86, area under the curve [AUC] = 0.48), whereas significant differences were observed for specific airway resistance from plethysmography (1.21 kPa/s [0.31] vs. 1.14 kPa/s [0.25]; +0.07 kPa/s [0.02-0.13]; P  < 0.01; AUC = 0.56) and spirometry forced expiratory volume in 1 second (FEV 1 ) % predicted (99.4% [12.0] vs. 102.6% [12.5]; -3.2% [-5.6 to -0.9]; P  < 0.01; AUC = 0.56) and forced expiratory flow at 25-75% (1.55 L/s [0.44] vs. 1.68 L/s [0.46]; -0.14 L/s [-0.22 to -0.05]; P  < 0.01; AUC = 0.58). FEV 1 (L/s) and FEV 1 /forced vital capacity ratio were not significantly different ( P  > 0.4). Conclusions: MBW, spirometry, and plethysmography are not sensitive tools for diagnosing mild asthmatic disease in young children.

Background: Studies have shown that airway obstruction and increased bronchial reactivity are present in early life in children developing asthma, which challenges the dogma that airway inflammation leads to low lung function. Further studies are needed to explore whether low lung function and bronchial hyperreactivity are inherent traits increasing the risk of developing airway inflammation and asthmatic symptoms in order to establish timely primary preventive initiatives., Methods and Findings: We investigated 367 (89%) of the 411 children from the at-risk Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC2000) birth cohort born to mothers with asthma, who were assessed by spirometry and bronchial reactivity to methacholine from age 1 month, plethysmography and bronchial reversibility from age 3 years, cold dry air hyperventilation from age 4 years, and exercise challenge at age 7 years. The COPSAC pediatricians diagnosed and treated asthma based on symptom load, response to inhaled corticosteroid, and relapse after treatment withdrawal according to a standardized algorithm. Repeated measures mixed models were applied to analyze lung function trajectories in children with asthma ever or never at age 1 month to 13 years. The number of children ever versus never developing asthma in their first 13 years of life was 97 (27%) versus 270 (73%), respectively. Median age at diagnosis was 2.0 years (IQR 1.2-5.7), and median remission age was 6.2 years (IQR 4.2-7.8). Children with versus without asthma had reduced lung function (z-score difference, forced expiratory volume, -0.31 [95% CI -0.47; -0.15], p < 0.001), increased airway resistance (z-score difference, specific airway resistance, +0.40 [95% CI +0.24; +0.56], p < 0.001), increased bronchial reversibility (difference in change in forced expiratory volume in the first second [ΔFEV1], +3% [95% CI +2%; +4%], p < 0.001), increased reactivity to methacholine (z-score difference for provocative dose, -0.40 [95% CI -0.58; -0.22], p < 0.001), decreased forced expiratory volume at cold dry air challenge (ΔFEV1, -4% [95% CI -7%; -1%], p < 0.01), and decreased forced expiratory volume after exercise (ΔFEV1, -4% [95% CI -7%; -1%], p = 0.02). Both airway obstruction and bronchial hyperreactivity were present before symptom debut, independent of disease duration, and did not improve with symptom remission. The generalizability of these findings may be limited by the high-risk nature of the cohort (all mothers had a diagnosis of asthma), the modest study size, and limited ethnic variation., Conclusions: Children with asthma at some point at age 1 month to 13 years had airway obstruction and bronchial hyperreactivity before symptom debut, which did not worsen with increased asthma symptom duration or attenuate with remission. This suggests that airway obstruction and bronchial hyperreactivity are stable traits of childhood asthma since neonatal life, implying that symptomatic disease may in part be a consequence of these traits but not their cause., Competing Interests: The authors have declared that no competing interests exists.

Aim: International collaboration is needed to enable large-scale pharmacogenomics studies in childhood asthma. Here, we describe the design of the Pharmacogenomics in Childhood Asthma (PiCA) consortium., Materials & Methods: Investigators of each study participating in PiCA provided data on the study characteristics by answering an online questionnaire., Results: A total of 21 studies, including 14,227 children/young persons (58% male), from 12 different countries are currently enrolled in the PiCA consortium. Fifty six percent of the patients are Caucasians. In total, 7619 were inhaled corticosteroid users. Among patients from 13 studies with available data on asthma exacerbations, a third reported exacerbations despite inhaled corticosteroid use. In the future pharmacogenomics studies within the consortium, the pharmacogenomics analyses will be performed separately in each center and the results will be meta-analyzed., Conclusion: PiCA is a valuable platform to perform pharmacogenetics studies within a multiethnic pediatric asthma population.

Background: Multiple breath washout (MBW) is an informative but time-consuming test. This study evaluates the uncertainty of a time-saving predictor algorithm in adolescents., Methods: Adolescents were recruited from the Copenhagen Prospective Study on Asthma in Childhood (COPSAC2000) birth cohort. MBW trials were performed at 13 y of age with Innocor model Inn00400 using sulfur hexafluoride (SF6) as tracer gas. Measurements were analyzed using a mixed model focusing on two prediction points doubling (t5%) and quadrupling (t10%) the standard end point (t2.5%)., Results: One hundred and seventy-two MBW trials conducted in 78 adolescents with and without asthma from COPSAC2000 were included. At t10%, the washout time (WoT) was reduced by 41%, and an uncertainty of 0.159 lung clearance index (LCI) units was introduced (±2 SD), ±1.27). At t5%, the WoT was reduced by 25%, with an uncertainty of 0.083 LCI units (±0.558). The optimal prediction point, which led to most saved time and least uncertainty was t5%., Conclusion: The predictor algorithm is capable of shortening the MBW test time but introduces an increasing uncertainty with earlier prediction points. This first-of-a-kind prediction algorithm holds promise in shortening the MBW test in children but should be used with caution in subjects with normal LCI values.

Importance: Observational studies have suggested that increased dietary vitamin D intake during pregnancy may protect against wheezing in the offspring, but the preventive effect of vitamin D supplementation to pregnant women is unknown., Objective: To determine whether supplementation of vitamin D3 during the third trimester of pregnancy reduces the risk of persistent wheeze in the offspring., Design, Setting, and Participants: A double-blind, single-center, randomized clinical trial conducted within the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort. Enrollment began March 2009 with a goal of 708 participants, but due to delayed ethical approval, only 623 women were recruited at 24 weeks of pregnancy. Follow-up of the children (N = 581) was completed when the youngest child reached age 3 years in March 2014., Interventions: Vitamin D3 (2400 IU/d; n = 315) or matching placebo tablets (n = 308) from pregnancy week 24 to 1 week postpartum. All women received 400 IU/d of vitamin D3 as part of usual pregnancy care., Main Outcomes and Measures: Age at onset of persistent wheeze in the first 3 years of life. Secondary outcomes included number of episodes of troublesome lung symptoms, asthma, respiratory tract infections, and neonatal airway immunology. Adverse events were assessed., Results: Of the 581 children, persistent wheeze was diagnosed during the first 3 years of life in 47 children (16%) in the vitamin D3 group and 57 children (20%) in the control group. Vitamin D3 supplementation was not associated with the risk of persistent wheeze, but the number of episodes of troublesome lung symptoms was reduced, and the airway immune profile was up-regulated (principal component analysis, P = .04). There was no effect on additional end points. Intrauterine death was observed in 1 fetus (<1%) in the vitamin D3 group vs 3 fetuses (1%) in the control group and congenital malformations in 17 neonates (5%) in the vitamin D3 group vs 23 neonates (8%) in the control group. [table: see text]., Conclusions and Relevance: The use of 2800 IU/d of vitamin D3 during the third trimester of pregnancy compared with 400 IU/d did not result in a statistically significant reduced risk of persistent wheeze in the offspring through age 3 years. However, interpretation of the study is limited by a wide CI that includes a clinically important protective effect., Trial Registration: clinicaltrials.gov Identifier: NCT00856947.

Background: Bacteria and viruses are equally associated with the risk of acute episodes of asthma-like symptoms in young children, suggesting antibiotics as a potential treatment for such episodes. We aimed to assess the effect of azithromycin on the duration of respiratory episodes in young children with recurrent asthma-like symptoms, hypothesising that it reduces the duration of the symptomatic period., Methods: In this randomised, double-blind, placebo-controlled trial, we recruited children aged 1-3 years, who were diagnosed with recurrent asthma-like symptoms from the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort; a birth cohort consisting of the general Danish population of Zealand, including Copenhagen. Exclusion criteria were macrolide allergy, heart, liver, neurological, and kidney disease, and, before each treatment, one or more clinical signs of pneumonia (respiratory frequency of ≥50 breaths per min; fever of ≥39°C; C-reactive protein concentration of ≥476·20 nmol/L [≥50 mg/L]). Each episode of asthma-like symptoms lasting at least 3 days was randomly allocated to a 3-day course of azithromycin oral solution of 10 mg/kg per day or placebo after thorough examination by a study physician at the Copenhagen Prospective Studies on Asthma research unit. Each episode was randomly allocated independently of previous treatment from a computer-generated list of random numbers in blocks of ten (generated at the Pharmacy of Glostrup). Investigators and children were masked until the youngest child turned 3 years of age and throughout the data validation and analysis phases. The primary outcome was duration of the respiratory episode after treatment, verified by prospective daily diaries and analysed with Poisson regression. Analyses were per protocol (excluding those without a primary outcome measure or who did not receive treatment). This trial is registered with ClinicalTrials.gov, number NCT01233297., Findings: Between Nov 17, 2010, and Jan 28, 2014, we randomly allocated 158 asthma-like episodes in 72 children (79 [50%] to azithromycin and 79 [50%] to placebo). The mean duration of the episode after treatment was 3·4 days for children receiving azithromycin compared with 7·7 days for children receiving placebo. Azithromycin caused a significant shortening of the episode of 63·3% (95% CI 56·0-69·3; p<0·0001). The effect size increased with early initiation of treatment, showing a reduction in episode duration of 83% if treatment was initiated before day 6 of the episode compared with 36% if initiated on or after day 6 (p<0·0001). We noted no differences in clinical adverse events between the azithromycin (18 [23%] of 78 episodes included in final analysis) and placebo (24 [30%] of 79) groups (p=0·30), but we did not investigate bacterial resistance patterns after treatment., Interpretation: Azithromycin reduced the duration of episodes of asthma-like symptoms in young children, suggesting that this drug could have a role in acute management of exacerbations. Further research is needed to disentangle the inflammatory versus antimicrobial aspects of this relation., Funding: Lundbeck Foundation, Danish Ministry of Health, Danish Council for Strategic Research, Capital Region Research Foundation., (Copyright © 2016 Elsevier Ltd. All rights reserved.)