Characterising resistance to fatigue crack growth in adhesive bonds by measuring release of strain energy

Measurement of the energy dissipation during fatigue crack growth is used as a technique to gain more insight into the physics of the crack growth process. It is shown that the amount of energy dissipation required per unit of crack growth is determined by Gmax, whereas the total amount of energy available for crack growth in a single cycle is determined by (Δ √g)2

Blood eosinophils and inhaled corticosteroid/long-acting β-2 agonist efficacy in COPD

Objective We performed a review of studies of fluticasone propionate (FP)/salmeterol (SAL) (combination inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA)) in patients with COPD, which measured baseline (pretreatment) blood eosinophil levels, to test whether blood eosinophil levels ≥2% were associated with a greater reduction in exacerbation rates with ICS therapy. Methods Three studies of ≥1-year duration met the inclusion criteria. Moderate and severe exacerbation rates were analysed according to baseline blood eosinophil levels (<2% vs ≥2%). At baseline, 57–75% of patients had ≥2% blood eosinophils. Changes in FEV1 and St George’s Respiratory Questionnaire (SGRQ) scores were compared by eosinophil level. Results For patients with ≥2% eosinophils, FP/SAL was associated with significant reductions in exacerbation rates versus tiotropium (INSPIRE: n=719, rate ratio (RR)=0.75, 95% CI 0.60 to 0.92, p=0.006) and versus placebo (TRISTAN: n=1049, RR=0.63, 95% CI 0.50 to 0.79, p<0.001). No significant difference was seen in the <2% eosinophil subgroup in either study (INSPIRE: n=550, RR=1.18, 95% CI 0.92 to 1.51, p=0.186; TRISTAN: n=354, RR=0.99, 95% CI 0.67 to 1.47, p=0.957, respectively). In SCO30002 (n=373), no significant effects were observed (FP or FP/SAL vs placebo). No relationship was observed in any study between eosinophil subgroup and treatment effect on FEV1 and SGRQ. Discussion Baseline blood eosinophil levels may represent an informative marker for exacerbation reduction with ICS/LABA in patients with COPD and a history of moderate/severe exacerbations

The nucleotide-binding domain and leucine-rich repeat protein-3 inflammasome is not activated in airway smooth muscle upon toll-like receptor-2 ligation

Inflammasomes have emerged as playing key roles in inflammation and innate immunity. A growing body of evidence has suggested that the nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasomeisimportant inchronic airwaydiseases suchas asthma and chronic obstructive pulmonary disease. Inflammasome activation results, in part, in pro-IL-1β processing and the secretion of the proinflammatory cytokine IL-1β. Because asthma exacerbations are associated with elevated concentrations of secreted IL-1β, we addressed whether the NLRP3 inflammasome is activated under in vitro conditions that mimic infectious exacerbations in asthma. Primary cultures of airway smoothmuscle (ASM) cells were treated with infectious stimuli (mimicked using the Toll-like receptor-2 agonist Pam3CSK4, a synthetic bacterial lipopeptide).Whereas Pam3CSK4 robustlyup-regulatedASMcytokineexpressionin response toTNF-αand significantly enhanced IL-1β mRNA expression, we were unable to detect IL-1β in the cell supernatants. Thus, IL-1β was not secreted and therefore was unable to act in an autocrine manner to promote the amplification of ASMinflammatory responses.Moreover, Toll-like receptor-2 ligation did not enhanceNLRP3 or caspase-1 expression in ASM cells, and NLRP3 and caspase-1 protein were not present in the ASM layer of tracheal sections from human donors. In conclusion, these data demonstrate that the enhanced synthetic function of ASM cells, induced by infectious exacerbations of airway inflammation, is NLRP3 inflammasome-independent and IL-1β-independent. Activation of the NLRP3 inflammasome by invading pathogens may prove cell type-specific in exacerbations of airway inflammation in asthma. Copyright © 2013 by the American Thoracic Society

Optimising use of electronic health records to describe the presentation of rheumatoid arthritis in primary care: a strategy for developing code lists

Background Research using electronic health records (EHRs) relies heavily on coded clinical data. Due to variation in coding practices, it can be difficult to aggregate the codes for a condition in order to define cases. This paper describes a methodology to develop ‘indicator markers’ found in patients with early rheumatoid arthritis (RA); these are a broader range of codes which may allow a probabilistic case definition to use in cases where no diagnostic code is yet recorded. Methods We examined EHRs of 5,843 patients in the General Practice Research Database, aged ≥30y, with a first coded diagnosis of RA between 2005 and 2008. Lists of indicator markers for RA were developed initially by panels of clinicians drawing up code-lists and then modified based on scrutiny of available data. The prevalence of indicator markers, and their temporal relationship to RA codes, was examined in patients from 3y before to 14d after recorded RA diagnosis. Findings Indicator markers were common throughout EHRs of RA patients, with 83.5% having 2 or more markers. 34% of patients received a disease-specific prescription before RA was coded; 42% had a referral to rheumatology, and 63% had a test for rheumatoid factor. 65% had at least one joint symptom or sign recorded and in 44% this was at least 6-months before recorded RA diagnosis. Conclusion Indicator markers of RA may be valuable for case definition in cases which do not yet have a diagnostic code. The clinical diagnosis of RA is likely to occur some months before it is coded, shown by markers frequently occurring ≥6 months before recorded diagnosis. It is difficult to differentiate delay in diagnosis from delay in recording. Information concealed in free text may be required for the accurate identification of patients and to assess the quality of care in general practice

Risk factors for exacerbations and pneumonia in patients with chronic obstructive pulmonary disease: a pooled analysis.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are at risk of exacerbations and pneumonia; how the risk factors interact is unclear. METHODS: This post-hoc, pooled analysis included studies of COPD patients treated with inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) combinations and comparator arms of ICS, LABA, and/or placebo. Backward elimination via Cox's proportional hazards regression modelling evaluated which combination of risk factors best predicts time to first (a) pneumonia, and (b) moderate/severe COPD exacerbation. RESULTS: Five studies contributed: NCT01009463, NCT01017952, NCT00144911, NCT00115492, and NCT00268216. Low body mass index (BMI), exacerbation history, worsening lung function (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage), and ICS treatment were identified as factors increasing pneumonia risk. BMI was the only pneumonia risk factor influenced by ICS treatment, with ICS further increasing risk for those with BMI <25 kg/m2. The modelled probability of pneumonia varied between 3 and 12% during the first year. Higher exacerbation risk was associated with a history of exacerbations, poorer lung function (GOLD stage), female sex and absence of ICS treatment. The influence of the other exacerbation risk factors was not modified by ICS treatment. Modelled probabilities of an exacerbation varied between 31 and 82% during the first year. CONCLUSIONS: The probability of an exacerbation was considerably higher than for pneumonia. ICS reduced exacerbations but did not influence the effect of risks associated with prior exacerbation history, GOLD stage, or female sex. The only identified risk factor for ICS-induced pneumonia was BMI <25 kg/m2. Analyses of this type may help the development of COPD risk equations

Patient characteristics associated with differences in patients' evaluation of their general practitioner

<p>Abstract</p> <p>Background</p> <p>Knowledge of the extent to which patient characteristics are systematically associated with variation in patient evaluations will enable us to adjust for differences between practice populations and thereby compare GPs. Whether this is appropriate depends on the purpose for which the patient evaluation was conducted. Associations between evaluations and patient characteristics may reflect gaps in the quality of care or may be due to inherent characteristics of the patients. This study aimed to determine such associations in a setting with a comprehensive list system and gate-keeping.</p> <p>Methods</p> <p>A nationwide Danish patient evaluation survey among voluntarily participating GPs using the EUROPEP questionnaire, which produced 28,260 patient evaluations (response rate 77.3%) of 365 GPs. In our analyses we compared the prevalence of positive evaluations in groups of patients.</p> <p>Results</p> <p>We found a positive GP assessment to be strongly associated with increasing patient age and increasing frequency of attendance. Patients reporting a chronic condition were more positive, whereas a low self-rated health was strongly associated with less positive scores also after adjustment. The association between patient gender and assessment was weak and inconsistent and depended on the focus. We found no association either with the patients' educational level or with the duration of listing with the GP even after adjusting for patient characteristics.</p> <p>Conclusion</p> <p>Adjustment for patient differences may produce a more fair comparison between GPs, but may also blur the assessment of GPs' ability to meet the needs of the populations actually served. On the other hand, adjusted results will enable us to describe the significance of specific patient characteristics to patients' experience of care.</p

Developmental Defects of Enamel in Primary Teeth and Association with Early Life Course Events: A Study of 6--36 Month old Children in Manyara, Tanzania.

Children with low birth weight show an increased prevalence of developmental defects of enamel in the primary dentition that subsequently may predispose to early childhood caries (ECC).Focusing 6--36 months old, the purpose of this study was to assess the frequency of enamel defects in the primary dentition and identify influences of early life course factors; socio-demographics, birth weight, child's early illness episodes and mothers' perceived size of the child at birth, whilst controlling for more recent life course events in terms of current breastfeeding and oral hygiene. A cross-sectional study was conducted in the high fluoride area of Manyara, northern Tanzania including 1221 child-mother pairs who attended Reproductive and Child Health (RCH) clinics for immunization and/or growth monitoring. After the primary caregivers had completed face to face interviews at the health care facility, children underwent oral clinical examination whereby ECC and developmental defects of enamel were recorded using field criteria. All erupted teeth were examined and the enamel defects were assessed on buccal surfaces according to the modified DDE Index. The prevalence of enamel defects was 33.3%. Diffuse opacities were the most common defects identified (23.1%), followed by hypoplasia (7.6%) and demarcated opacities (5.0%). The most frequently affected teeth were the upper central incisors (29.0% - 30.5%), whereas lower central incisors (4.3% to 4.5%) were least frequently affected. Multiple logistic regression analysis, adjusting for confounding the factors revealed that having normal birth weight (equal or more than 2500 g) associated with lower odds of having enamel hypoplasia [OR 0.22 (95% CI 0.1-0.7)]. No statistically significant association occurred between birth weight and diffuse opacities, demarcated opacities or combined DDE. Children with the history of low birth weight were more likely than their normal birth weight counterparts to present with enamel hypoplasia. In view of the frequent occurrence of enamel defects and the fact that hypoplasia may constitute a risk factor for future ECC, enamel defects should be included as a dental health indicator in epidemiological studies of children in northern Tanzania

Adolescent standing postural response to backpack loads: a randomised controlled experimental study

BACKGROUND: Backpack loads produce changes in standing posture when compared with unloaded posture. Although 'poor' unloaded standing posture has been related to spinal pain, there is little evidence of whether, and how much, exposure to posterior load produces injurious effects on spinal tissue. The objective of this study was to describe the effect on adolescent sagittal plane standing posture of different loads and positions of a common design of school backpack. The underlying study aim was to test the appropriateness of two adult 'rules-of-thumb'-that for postural efficiency, backpacks should be worn high on the spine, and loads should be limited to 10% of body weight. METHOD: A randomised controlled experimental study was conducted on 250 adolescents (12–18 years), randomly selected from five South Australian metropolitan high schools. Sagittal view anatomical points were marked on head, neck, shoulder, hip, thigh, knee and ankle. There were nine experimental conditions: combinations of backpack loads (3, 5 or 10% of body weight) and positions (backpack centred at T7, T12 or L3). Sagittal plane photographs were taken of unloaded standing posture (baseline), and standing posture under the experimental conditions. Posture was quantified from the x (horizontal) coordinate of each anatomical point under each experimental condition. Differences in postural response were described, and differences between conditions were determined using Analysis of Variance models. RESULTS: Neither age nor gender was a significant factor when comparing postural response to backpack loads or conditions. Backpacks positioned at T7 produced the largest forward (horizontal) displacement at all the anatomical points. The horizontal position of all anatomical points increased linearly with load. CONCLUSION: There is evidence refuting the 'rule-of-thumb' to carry the backpack high on the back. Typical school backpacks should be positioned with the centre at waist or hip level. There is no evidence for the 10% body weight limit