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The word ‘Islam’ is originated from the word ‘Silm’ which means peace. If a logical and a reasonable person tries to study Islam neutrally, he will come to know that ‘peace’ is present in all the teachings of Islam. In pursuit of that peace a Muslim need to follow Islamic guidelines properly. As soon as he trends that path, he will start having peace. In this article it was tried to mention responsibilities of parents and teachers towards children’s education in the light of Islam. These responsibilities stretch from the religious education to the physical education of the children. It is discussed thoroughly that what is the role of Muslim parents and the teachers in raising the children safe and sound and in line with the instructions of the holy Quran and the traditions and biography of the holy Prophet (May Allah be pleased with him).

Dr.Mahmood Ahmad Ghazi (1950-2010) was a great scholar of the modern era. His scholarly work has been published in various Islamic fields. His special area of interest was Islamic Jurisprudence, Objectives of Shariah and Islamic International Law, but his contribution in Seerah studies was also recognized in academic circles for his multidimensional and critical approaches and work, scattered in various books,lectures,papers,review notes and prefaces of literary books.Most of his important work was produced by his well-known lectures”Muhazarat-i-seerat”. His research includes Prophetic Hijrah, Seerah evolution and Seerah writers, Orientalists contributions and its criticism, Muslim Response to orientalisam, Fiqh Us Seerah, Seerah writings in Sub- Continent and contemporey trends in Seerah.This article eloborates his Seerah Contribution by analyzing his work and highlighting its nevelity.

Janelle Yorke,1,2 Naimat Khan,1,3 Adam Garrow,1 Sarah Tyson,1 Dave Singh,1,3 Jorgen Vestbo,1,4 Paul W Jones5 1Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK; 2Christie Patient Centred Research, The Christie NHS Foundation Trust, Whittington, Manchester, UK; 3Medicines Evaluation Unit, Wythenshawe, Manchester, UK; 4Department of Respiratory Medicine, Wythenshawe Hospital, Manchester, UK; 5St George’s Hospital, University of London, London, UKCorrespondence: Janelle Yorke, Tel +44920 264411, Email janelle.yorke@nhs.netPurpose: The modified-Medical Research Council (mMRC) breathlessness scale consists of five grades that contain of a description of different activities. It has wide utility in the assessment of disability due to breathlessness but was originally developed before the advent of modern psychometric methodology and, for example contains more than one activity per grade. We conducted an evaluation of the mMRC structure.Patients and Methods: Cognitive debriefing was conducted with COPD patients to elicit their understanding of each mMRC activity. In a cross-sectional study, patients completed the mMRC scale (grades 0– 4) and an MRC-Expanded (MRC-Ex) version consisting of 10-items, each containing one mMRC activity. Each activity was then given a 4-point response scale (0 “not at all” to 4 “all of the time”) and all 10 items were given to 203 patients to complete Rasch analysis and assess the pattern of MRC item severity and its hierarchical structure.Results: Cognitive debriefing with 36 patients suggested ambiguity with the term “strenuous exercise” and perceived severity differences between mMRC activities. 203 patients completed the mMRC-Ex. Strenuous exercise was located third on the ascending severity scale. Rasch identified the mildest term was “walking up a slight hill” (logit − 2.76) and “too breathless to leave the house” was the most severe (logit 3.42).Conclusion: This analysis showed that items that were combined into a single mMRC grade may be widely separated in terms of perceived severity when assessed individually. This suggests that mMRC grades as a measure of individual disability related to breathlessness contain significant ambiguity due to the combination of activities of different degrees of perceived severity into a single grade.Keywords: psychometrics, Rasch analysis, patient reported outcomes, qualitative, scale development

Islam guides its followers in every field of life. It requires from Muslims to search solutions of emerging problems keeping in view the golden rules set by the Quran and the Sunnah. Advertising along with its recent ways is somehow a new phenomenon. This study aims to explore antecedences of advertising in the holy Quran and the Traditions of the holy Prophet. (May peace and mercy be upon him.) Firstly, the two meanings of advertising are mentioned, and the examples of both meanings are presented from the Quran, the Traditions of the holy Prophet (PBUH) and the life of one of the holy companions of the Prophet. Secondly shariah ruling of the advertising is discussed in the light of the sources of the shariah. Lastly the results of the study are stated that read: Keeping in view the cases of the advertising from the Traditions of the holy Prophet (PBUH) and bearing in mind importance and need of it in current times, it is clear that publishing ads and broadcasting them for the promotion of the goods or services is basically allowed unless something contradictory to Islam is added to it, like lies, deception, exaggeration, degrading of other’s goods and display of half naked women etc.

Research Question: Does the introduction of Key Audit Matters (KAMs) increase audit quality and reduce agency cost associated with it? Does the introduction of KAMs decrease Earnings Management (EM) and agency cost associated with it? Motivation: There have been many studies in the past few years testing the impact of KAMs on the quality of the audit and EM in the developed economies like the United States and United Kingdom, however very few studies exist in the context of the UAE. Moreover, many studies on this topic uses quantitative techniques whereas this study employs qualitative method of interview to judge the perception of auditors about the audit quality and EM in the UAE after the introduction of KAMs. Idea: The research seeks the perception of auditors about the quality of audit and EM after the introduction of communicating KAMs in the UAE. Data and Tools: A semi-structured interview is conducted with thirteen auditors –six Big-4 and seven Non-Big 4 audit firms. Findings: The findings show that the introduction of KAMs enhances the quality of audit in the form of better communication and transparency, especially, in big listed firms. It increases the managerial accountability which results in minimizing the agency cost of equity. However, the study also reveals that the auditors have the audacity to confess the pressures from clients and audit firms which lead to the hidden anomalies and EM practices that resulted in decreasing the audit quality, especially in non-Big 4 firms. Contribution: The research shows that there is no uniformity in audit practice in UAE where own nationals (Emirates) enjoy more flexibility compare to foreigners. In addition, a difference exists in the audit practices of Big-4 and Non-Big 4 auditors. The non-existence of stringent audit regulatory body lead to effect the overall quality of the audit. The government should implement a uniform and robust audit regulatory body to ensure the audit quality.

Background The effects of triple therapy on gas trapping in COPD are not fully understood. We evaluated the effects of the long acting bronchodilator components of the extrafine single inhaler triple therapy beclometasone dipropionate/formoterol/glycopyrronium (BDP/F/G) pMDI on gas trapping. Methods This open-label, randomised, single centre, 2-way cross-over study recruited 23 COPD patients taking inhaled corticosteroid combination treatments and with residual volume (RV) > 120% predicted at screening. Inhaled BDP was taken during run-in and washout periods. Baseline lung function (spirometry, lung volumes, oscillometry) was measured over 12 h prior to randomisation to BDP/F/G or BDP/F for 5 days followed by washout and crossover. Lung function was measured prior to dosing on day 1 and for 12 h post-dose on day 5. Results Co-primary endpoint analysis: BDP/F/G had a greater effect than BDP/F on FEV1 area under the curve over 12 h (AUC0–12) (mean difference 104 mls, p = 0.0071) and RV AUC0–12 (mean difference − 163 mls, p = 0.0028). Oscillometry measurements showed a greater effect of BDP/F/G on the difference between resistance at 5 and 20 Hz (R5–R20) AUC0–12, which measures small airway resistance (mean difference − 0.045 kPa/L/s, p = 0.0002). Comparison of BDP/F with the baseline measurements (BDP alone) showed that F increased FEV1 AUC0–12 (mean difference 227 mls) and improved RV AUC0–12 (mean difference − 558 mls) and R5–R20 AUC0–12 (mean difference − 0.117 kPa/L/s), all p Conclusions In COPD patients with hyperinflation, the G and F components of extrafine BDP/F/G improved FEV1, RV and small airway function. These long acting bronchodilators target small airway function, thereby improving gas trapping and airflow. Trial registration The study was retrospectively registered at ClinicalTrials.gov on 15th February 2019 (No.: NCT03842904, https://clinicaltrials.gov/ct2/show/NCT03842904).

The institution of ‘Gift’ (ہبہ) is common in every religion. Every religion promo-tes this practice, as it is a tool to create sense of love and affection between the giver and the receiver. Similarly, Islam encourages its followers to perform it from time to time and spread sense of love and affection. The holy Prophet (Peace and Mercy be upon him) not only ordered the believers of Islam to exchange gifts but also, he himself was habitual of distributing things among the Muslims as gifts. Here, in this article, this exercise of the ‘Gift’ is discussed. Firstly, its lexical and terminological meanings are mentioned and supported with verses of the holy Quran and the traditions of the holy Prophet (PBUH). Furthermore, its need and importance are given consideration. Secondly, kinds of the ‘Gift’ are specified, which are ‘Gift of existing things and non-existing things’. Then the existing things are divided into ‘Devisable and non-devisable items’. In the end the concept of possession in the ‘Gift’ is stated. Along with all this opinions of the five schools of thoughts i.e. Hanafi, Maliki, Shafai, Hanbali and Shia, and their basis regarding possession of the ‘Gift’ are presented.

Methacholine challenges have been used in clinical trials to assess therapeutic effects and potential adverse reactions of interventions on pulmonary function in a sensitive population, such as in subjects with asthma. Here, we evaluate the variability of the methacholine challenge recovery model, and compare the results obtained for both incremental and bolus challenge methods.The extent, time course and variability of change in forced expiratory volume in 1 s (FEVA total of 19 subjects were included in the study. Both the mean FEVMaximum reduction in FEV

Aims Oral itraconazole has variable pharmacokinetics and risks of adverse events associated with high plasma exposure. An inhalation formulation of itraconazole (PUR1900) is being developed to treat allergic bronchopulmonary aspergillosis, an allergic inflammatory disease occurring in asthmatics and patients with cystic fibrosis. Methods A 3-part, open-label Phase 1 study was conducted to evaluate safety, tolerability and pharmacokinetics of PUR1900. Healthy volunteers (n = 5-6/cohort) received either single (Part 1) or multiple (Part 2) ascending doses of PUR1900 for up to 14 days. In Part 3 stable, adult asthmatics received a single dose of 20 mg PUR1900 or 200 mg of oral Sporanox (itraconazole oral solution) in a 2-period randomized cross-over design. Itraconazole plasma and sputum concentrations were evaluated. Results None of the adverse events considered as at least possibly related to study treatment were moderate or severe, and none were classed as serious. The most common was the infrequent occurrence of mild cough. Itraconazole plasma exposure increased with increasing doses of PUR1900. After 14 days, PUR1900 resulted in plasma exposure (area under the concentration-time curve up to 24 h) 106- to 400-fold lower across doses tested (10-35 mg) than steady-state exposure reported for oral Sporanox 200 mg. In asthmatics, PUR1900 geometric mean maximum sputum concentrations were 70-fold higher and geometric mean plasma concentrations were 66-fold lower than with oral Sporanox. Conclusion PUR1900 was safe and well-tolerated under the study conditions. Compared to oral dosing, PUR1900 achieved higher lung and lower plasma exposure. The pharmacokinetic profile of PUR1900 suggests the potential to improve upon the efficacy and safety profile observed with oral itraconazole.

Rhinovirus (RV) infections are a major cause of exacerbations in patients with asthma. Experimental RV challenges can provide insight into the pathophysiology of viral exacerbations. Previous reports, investigating mild or moderate asthma patients, have shown an upregulation in type 2 inflammation post RV infection, however, studies specifically involving asthma patients taking inhaled corticosteroids have concentrated on symptoms and lung function, rather than the inflammatory response.Eleven moderate asthma patients were inoculated with RV. Cold symptoms and asthma control were assessed at baseline and post infection. Nasal epithelial lining fluid and bronchial alveolar lavage (BAL) fluid were collected at baseline and 4 days post infection for assessment of inflammatory proteins.Patients suffered increased cold symptoms and decreased asthma control within 7 days of infection. Antiviral mechanisms were induced following inoculation, with increases in interferon -α, β, γ and λ, as well as CXCL10 and CXCL11. Type 2 inflammatory cytokines were also significantly elevated post RV infection in both nasal and bronchial samples. In BAL, epithelial derived IL-25 and IL-33 levels strongly correlated with Th2 cytokines, IL-4, IL-5 and IL-13.We show how experimental rhinovirus challenge regulates lung and nasal biomarkers in asthma patients taking inhaled corticosteroids. These biomarkers could be used to evaluate the effects of novel drugs for asthma.

Background Methacholine challenges have been used in clinical trials to assess therapeutic effects and potential adverse reactions of interventions on pulmonary function in a sensitive population, such as in subjects with asthma. Here, we evaluate the variability of the methacholine challenge recovery model, and compare the results obtained for both incremental and bolus challenge methods. Methods The extent, time course and variability of change in forced expiratory volume in 1 s (FEV1) following repeated methacholine challenges in subjects with mild asthma were investigated in an open-label, four-period, fixed-sequence, two-method, replicate crossover study. At Visits 1 and 2, subjects underwent an incremental challenge using doubling doses of methacholine until a ≥20% decrease in FEV1 was observed; at Visits 3 and 4, subjects underwent a bolus challenge, inhaling a single dose of methacholine calculated from the cumulative dose established during Visit 1. Results A total of 19 subjects were included in the study. Both the mean FEV1 area under the curve (FEV1 AUC0–tz) and mean maximum reductions in FEV1 (absolute and relative) 120 min post-challenge values were higher for the incremental challenges than the bolus challenges, with no reported difference between repetitions of the same methodology. FEV1 AUC0–tz decrease 120 min post challenge demonstrated an intra-subject coefficient of variation (CV) of 47.2% (incremental) and 78.3% (bolus), suggesting considerable between-visit variability. The mean absolute, and similarly relative, maximum reductions in FEV1 compared with post-diluent baseline values demonstrated lower intra-subject variability (incremental 21.16%, bolus 40.67%) than the FEV1 AUC0–tz-based endpoint. There was a trend towards faster recovery following the bolus challenge than with the incremental challenge. The provocative dose of methacholine inducing a ≥20% decrease in FEV1 resulted in a between-group mean difference of 27.20% in the incremental challenge periods, with a high intra-subject CV of 80.64%, demonstrating considerable variability. Conclusion Maximum reduction in FEV1 had the lowest variability. There was little difference between repetitions of the same methodology, as indicated by overlapping confidence intervals. There was a trend towards faster recovery following bolus challenge than with the incremental challenge. The results of this trial could be of value when designing future clinical trials using the methacholine challenge methodology.

Aims Some asthma patients remain symptomatic despite using high doses of inhaled corticosteroids (ICS). We used alveolar macrophages to identify individual patients with insensitivity to corticosteroids and to evaluate the anti-inflammatory effects of a p38 mitogen-activated protein kinase (MAPK) inhibitor combined with a corticosteroid on these cells. Methods Alveolar macrophages from 27 asthma patients (classified according to the Global Initiative for Asthma (GINA) treatment stage. Six GINA1, 10 GINA2 and 11 GINA3/4) were stimulated with lipoploysaccharide (LPS) (1 μg ml−1). The effects of dexamethasone (dex 1–1000 nm), the p38 MAPK inhibitor 1-(5-tert-butyl-2-p-tolyl-2Hpyrazol-3-yl)-3(4-(2-morpholin-4-yl-ethoxy)naphthalen-1-yl)urea (BIRB-796 1–1000 nm) and both drugs combined at all concentrations on supernatant TNFα, IL-6 and CXCL-8 concentrations were analyzed by ELISA. Dose-sparing and efficacy enhancing effects of combination treatment were determined. Results Dexamethasone reduced LPS-induced TNFα, IL-6 and CXCL-8 in all groups, but maximum inhibition was significantly reduced for GINA3/4 compared with GINA2 and GINA1 (P < 0.01). A subgroup of corticosteroid insensitive patients with a reduced effect of dexamethasone on cytokine secretion were identified. BIRB-796 in combination with dexamethasone significantly increased cytokine inhibition compared with either drug alone (P < 0.001) in all groups. This effect was greater in corticosteroid insensitive compared with sensitive patients. There were significant synergistic dose-sparing effects (P < 0.05) for the combination treatment on inhibition of TNFα, IL-6 and CXCL-8 in all groups. There was also significant efficacy enhancing benefits (P < 0.05) on TNFα and IL-6. Conclusions p38 MAPK inhibitors synergistically enhance efficacy of corticosteroids in macrophages from asthma patients. This effect is greater in corticosteroid insensitive asthma patients, suggesting that this class of drug should be targeted to this patient phenotype.

BACKGROUND: Sleep problems are common in patients with chronic obstructive pulmonary disease (COPD), but the validity of patient-reported outcome measures (PROMs) that measure sleep dysfunction has not been evaluated. We have reviewed the literature to identify disease-specific and non-disease-specific sleep PROMs that have been validated for use in COPD patients. The review also examined the psychometric properties of identified sleep outcome measures and extracted point and variability estimates of sleep instruments used in COPD studies. METHODS: The online EMBASE, MEDLINE, PsycINFO, and SCOPUS databases for all years to May 2014 were used to source articles for the review. The review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Criteria from the Medical Outcomes Trust Scientific Advisory Committee guidelines were used to evaluate the psychometric properties of all sleep PROMs identified. RESULTS: One COPD-specific and six non-COPD-specific sleep outcome measures were identified and 44 papers met the review selection criteria. We only identified one instrument, the COPD and Asthma Sleep Impact Scale, which was developed specifically for use in COPD populations. Ninety percent of the identified studies used one of two non-disease-specific sleep scales, ie, the Pittsburgh Sleep Quality Index and/or the Epworth Sleep Scale, although neither has been tested for reliability or validity in people with COPD. CONCLUSION: The results highlight a need for existing non-disease-specific instruments to be validated in COPD populations and also a need for new disease-specific measures to assess the impact of sleep problems in COPD.

AimEarly morning symptoms (EMS) in people with COPD are associated with poor health, impaired activities and increased exacerbation risk. We describe the development and preliminary validation of the Manchester Early Morning Symptom Index (MEMSI) to quantify EMS in COPD.MethodsFocus groups and cognitive debriefing with patients with COPD were used to develop the potential item list, followed by a cross-sectional study to finalise the items for inclusion. In addition to test-retest reliability, comparisons with the St George's Respiratory Questionnaire-C (SGRQ-C), modified Medical Research Council Dyspnoea Scale, Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F) and Hospital Anxiety and Depression Scale (HADS) evaluated construct validity. Hierarchical methods informed item deletion and Rasch analysis was applied to assess scale unidimensionality.Results23 items were identified from the focus groups and debriefings. The cross-sectional study involved 203 patients with COPD (mean age 64.7 SD 7.5 years, male 63%, Global Initiative for Chronic Obstructive Lung Disease (GOLD): 1:14% 2:41% 3:25% 4: 7%). 13 items were removed during item reduction. MEMSI contains 10 items, demonstrates good overall fit to the Rasch model (χ2 p=0.26) and item score distribution; excellent reliability (Person Separation Index: 0.91) and good test-retest repeatability (r=0.82). It correlates with the SGRQ-C (r=0.73), FACIT-F (r=−0.65) and HADS (r=0.53–0.54) indicating good construct validity.ConclusionsMEMSI is a reliable and valid unidimensional measure of EMS for patients with COPD. It is simple to use and score supporting its suitability for research and clinical use. Work is underway to determine the minimal clinical important difference and cross-cultural validity.

Air pollution by diesel exhaust particles is associated with elevated mortality and increased hospital admissions in\ud individuals with respiratory diseases such as asthma and chronic obstructive pulmonary disease. During active inflammation\ud monocytes are recruited to the airways and can replace resident alveolar macrophages. We therefore investigated whether\ud chronic fourteen day exposure to low concentrations of diesel exhaust particles can alter the phenotype and function of\ud monocytes from healthy individuals and those with chronic obstructive pulmonary disease. Monocytes were purified from\ud the blood of healthy individuals and people with a diagnosis of chronic obstructive pulmonary disease. Monocyte-derived\ud macrophages were generated in the presence or absence of diesel exhaust particles and their phenotypes studied through\ud investigation of their lifespan, cytokine generation in response to Toll like receptor agonists and heat killed bacteria, and\ud expression of surface markers. Chronic fourteen day exposure of monocyte-derived macrophages to concentrations of\ud diesel exhaust particles .10 mg/ml caused mitochondrial and lysosomal dysfunction, and a gradual loss of cells over time\ud both in healthy and chronic obstructive pulmonary disease individuals. Chronic exposure to lower concentrations of diesel\ud exhaust particles impaired CXCL8 cytokine responses to lipopolysaccharide and heat killed E. coli, and this phenotype was\ud associated with a reduction in CD14 and CD11b expression. Chronic diesel exhaust particle exposure may therefore alter\ud both numbers and function of lung macrophages differentiating from locally recruited monocytes in the lungs of healthy\ud people and patients with chronic obstructive pulmonary disease.

Introduction and Objectives Alveolar macrophages are heavily implicated in the pathogenesis COPD. During chronic inflammation, macrophages mature continuously from infiltrating monocytes that are continually recruited to the airways. We have previously found DEP modulate life span and function of monocytes from healthy donors, but their effects on monocytes of people with COPD are unknown, and were therefore the subject of this study. Methods Monocytes were purified from the blood of patients with GOLD II/III COPD and healthy age matched controls Monocyte-derived macrophages (MDMs) were generated in the presence or absence of DEP and their lifespan studied. Cytokine generation in response to TLR agonists and heat killed bacteria was assessed by ELISA and expression of CD14 was measured by FACS. Results Chronic exposure of monocytes from patients with COPD to DEP concentrations above 10 μg/ml caused a significant reduction in cell survival. Lower concentration of chronic DEP exposure, as low as 1 μg/ml, caused impairment of cytokine responses to LPS and heat killed Escherichia Coli , and this phenotype was associated with a reduction in CD14 surface marker expression. However, COPD monocytes were generally more resistant to the effects of DEP compared to healthy control cells. Conclusions In this study monocytes from healthy volunteers appeared to be more susceptible to the harmful effects of chronic DEP exposure compared to those from individuals with COPD. These findings reinforce the evidence that circulating leukocytes in COPD patients have altered phenotypes.

Introduction: The MRC dyspnoea scale consists of 5 grades that contain of a description of more than one activity. The comparability of these components is not known. We examined the performance of single descriptors of each MRC grade. Methods: Phase I: cognitive debriefing with COPD patients to elicit their understanding of each activity (10 items) of the 5 MRC grades. Phase II: COPD patients completed the MRC scale (grades 1-4) and a MRC-Exploded (MRC-Ex) consisting of 10-items, each representing one activity as described in the MRC grades. Each item used a 4-point response scale (0 9not at all9 to 4 9all of the time9). Rasch analysis was used to assess the pattern of MRC-Ex item severity (logit) to assess the appropriateness of combining individual activity descriptors into single MRC grades. Results: Cognitive debriefing (n=36) identified: MRC 1: meaning of 9strenuous exercise9 unclear and MRC 5: 9too breathless to leave the house9 viewed as “much worse than being breathless with dressing”. 203 patients completed Phase II (mean age 64.7years, GOLD: 1:14% 2:41% 3:25% 4:7%). MRC components 3, 4 and 5 are not of equivalent severity, with grade 5 components at least 2 logits apart Conclusions: The MRC has poor reliability due to ambiguity in the degree of severity of the items in Grades 1 and 5. We recommend that 9strenuous exercise9 is removed from MRC grading and that Grade 5 forms separate grades, in particular.