Wing Panel Design with Novel Skin-Buckling Containment Features

The impact of buckling containment features on the stability of thin-gauge fuselage, metallic stiffened panels has previously been demonstrated. With the continuing developments in manufacturing technology, such as welding, extrusion, machining, and additive layer manufacture, understanding the benefits of additional panel design features on heavier applications, such as wing panels, is timely. This compression testing of thick-gauge panels with and without buckling containment features has been undertaken to verify buckling and collapse behaviors and validate sizing methods. The experimental results demonstrated individual panel mass savings on the order of 9%, and wing cover design studies demonstrated mass savings on the order of 4 to 13%, dependent on aircraft size and material choice.

The effect of manufacture and assembly joining methods on stiffened panel performance

This paper describes the simulation of representative aircraft wing stiffened panels under axial compression loading, to determine the effects of varying the manufacturing shape and assembly joining methods on stiffened panel performance. T-stiffened and Z-stiffened panels are modelled in Abaqus simulating integral, co-cured and mechanically fastened joints. The panels are subject to an edge compressive displacement along the stiffener axis until failure and the ultimate failure load and buckling performance is assessed for each. Integral panels consistently offer the highest performance. Co-cured panels demonstrate reduced performance (3-5% reduction in ultimate load relative to integral) caused by localised cohesive failure and skin-stiffener separation. The mechanically fastened panels are consistently the weakest joint (19-25% reduction in ultimate load relative to integral) caused primarily by inter-rivet buckling between fasteners

Treatment of Unexplained Chronic Cough: CHEST Guideline and Expert Panel Report

Background: Unexplained chronic cough (UCC) causes significant quality of life impairment. There is a need to identify effective assessment and treatment approaches for UCC.

Methods: This systematic review of randomized controlled clinical trials asked: What is the efficacy of treatment compared to usual care on cough severity, cough frequency, and cough-related quality of life in patients with unexplained chronic cough (UCC)? Studies of adults and adolescents >12 years with a chronic cough of >8 weeks duration that was unexplained after systematic investigation and treatment were included and assessed for relevance and quality. Based upon the systematic review, guideline suggestions were developed and voted upon using CHEST organization methodology.

Results: 11 RCTs and 5 systematic reviews were included. The 11 RCTs reported data on 570 participants with chronic cough who received a variety of interventions. Study quality was high in 10 RCTs. The studies used a variety of descriptors and assessments to identify unexplained chronic cough. While gabapentin and morphine showed positive effects on cough-related quality of life, only gabapentin was supported as a treatment recommendation. Studies of inhaled corticosteroids (ICS) suffered from intervention fidelity bias, and when this was addressed, ICS were not found to be effective for UCC. Esomeprazole was not effective for UCC without features of gastroesophageal acid reflux. Studies addressing non-acid gastroesophageal reflux were not identified. A multimodality speech pathology intervention improved cough severity.

Conclusions: The evidence supporting the diagnosis and management of UCC is limited. UCC requires further study to establish agreed terminology and the optimal methods of investigation using established criteria for intervention fidelity. Speech pathology based cough suppression is suggested as a treatment option for UCC. This guideline presents suggestions for diagnosis and treatment based on the best available evidence and identifies gaps in our knowledge and areas for future research.

Assessment of Intervention Fidelity and Recommendations for Researchers Conducting Studies on the Diagnosis and Treatment of Chronic Cough in the Adult: CHEST Guideline and Expert Panel Report

BACKGROUND: Successful management of chronic cough has varied in the primary research studies in the reported literature. One of the potential reasons relates to a lack of intervention fidelity to the core elements of the diagnostic and/or therapeutic interventions that were meant to be used by the investigators.

METHODS: We conducted a systematic review to summarize the evidence supporting intervention fidelity as an important methodologic consideration in assessing the effectiveness of clinical practice guidelines used for the diagnosis and management of chronic cough. We developed and used a tool to assess for five areas of intervention fidelity. Medline (PubMed), Scopus, and the Cochrane Database of Systematic Reviews were searched from January 1998 to May 2014. Guideline recommendations and suggestions for those conducting research using guidelines or protocols to diagnose and manage chronic cough in the adult were developed and voted upon using CHEST Organization methodology.

RESULTS: A total of 23 studies (17 uncontrolled prospective observational, two randomized controlled, and four retrospective observational) met our inclusion criteria. These articles included 3,636 patients. Data could not be pooled for meta-analysis because of heterogeneity. Findings related to the five areas of intervention fidelity included three areas primarily related to the provider and two primarily related to the patients. In the area of study design, 11 of 23 studies appeared to be underpinned by a single guideline/protocol; for training of providers, two of 23 studies reported training, and zero of 23 reported the use of an intervention manual; and for the area of delivery of treatment, when assessing the treatment of gastroesophageal reflux disease, three of 23 studies appeared consistent with the most recent guideline/protocol referenced by the authors. For receipt of treatment, zero of 23 studies mentioned measuring concordance of patient-interventionist understanding of the treatment recommended, and zero of 23 mentioned measuring enactment of treatment, with three of 23 measuring side effects and two of 23 measuring adherence. The overall average intervention fidelity score for all 23 studies was poor (20.74 out of 48).

CONCLUSIONS: Only low-quality evidence supports that intervention fidelity strategies were used when conducting primary research in diagnosing and managing chronic cough in adults. This supports the contention that some of the variability in the reporting of patients with unexplained or unresolved chronic cough may be due to lack of intervention fidelity. By following the recommendations and suggestions in this article, researchers will likely be better able to incorporate strategies to address intervention fidelity, thereby strengthening the validity and generalizability of their results that provide the basis for the development of trustworthy guidelines.

Cross-section and panel estimates of peer effects in early adolescent cannabis use: With a little help from my ‘friends once removed’

Peer effects in adolescent cannabis are difficult to estimate, due in part to the lack of appropriate data on behaviour and social ties. This paper exploits survey data that have many desirable properties and have not previously been used for this purpose. The data set, collected from teenagers in three annual waves from 2002-2004 contains longitudinal information about friendship networks within schools (N = 5,020). We exploit these data on network structure to estimate peer effects on adolescents from their nominated friends within school using two alternative approaches to identification. First, we present a cross-sectional instrumental variable (IV) estimate of peer effects that exploits network structure at the second degree, i.e. using information on friends of friends who are not themselves ego’s friends to instrument for the cannabis use of friends. Second, we present an individual fixed effects estimate of peer effects using the full longitudinal structure of the data. Both innovations allow a greater degree of control for correlated effects than is commonly the case in the substance-use peer effects literature, improving our chances of obtaining estimates of peer effects than can be plausibly interpreted as causal. Both estimates suggest positive peer effects of non-trivial magnitude, although the IV estimate is imprecise. Furthermore, when we specify identical models with behaviour and characteristics of randomly selected school peers in place of friends’, we find effectively zero effect from these ‘placebo’ peers, lending credence to our main estimates. We conclude that cross-sectional data can be used to estimate plausible positive peer effects on cannabis use where network structure information is available and appropriately exploited.

Inter-Laboratory Evaluation of a Next-Generation Sequencing Panel for Acute Myeloid Leukemia

INTRODUCTION: Acute myeloid leukemia (AML) is a heterogeneous clonal disorder often associated with dismal overall survival. The clinical diversity of AML is reflected in the range of recurrent somatic mutations in several genes, many of which have a prognostic and therapeutic value. Targeted next-generation sequencing (NGS) of these genes has the potential for translation into clinical practice. In order to assess this potential, an inter-laboratory evaluation of a commercially available AML gene panel across three diagnostic centres in the UK and Ireland was performed.

METHODS: DNA from six AML patient samples was distributed to each centre and processed using a standardised workflow, including a common sequencing platform, sequencing chips and bioinformatics pipeline. A duplicate sample in each centre was run to assess inter- and intra-laboratory performance.

RESULTS: An average sample read depth of 2725X (range 629-5600) was achieved using six samples per chip, with some variability observed in the depth of coverage generated for individual samples and between centres. A total of 16 somatic mutations were detected in the six AML samples, with a mean of 2.7 mutations per sample (range 1-4) representing nine genes on the panel. 15/16 mutations were identified by all three centres. Allelic frequencies of the mutations ranged from 5.6 to 53.3 % (median 44.4 %), with a high level of concordance of these frequencies between centres, for mutations detected.

CONCLUSION: In this inter-laboratory comparison, a high concordance, reproducibility and robustness was demonstrated using a commercially available NGS AML gene panel and platform.

BRAF mutation testing algorithm for vemurafenib treatment in melanoma: recommendations from an expert panel.

The incidence of melanoma has increased rapidly over the past 30 years, and the disease is now the sixth most common cancer among men and women in the U.K. Many patients are diagnosed with or develop metastatic disease, and survival is substantially reduced in these patients. Mutations in the BRAF gene have been identified as key drivers of melanoma cells and are found in around 50% of cutaneous melanomas. Vemurafenib (Zelboraf(®) ; Roche Molecular Systems Inc., Pleasanton, CA, U.S.A.) is the first licensed inhibitor of mutated BRAF, and offers a new first-line option for patients with unresectable or metastatic melanoma who harbour BRAF mutations. Vemurafenib was developed in conjunction with a companion diagnostic, the cobas(®) 4800 BRAF V600 Mutation Test. The purpose of this paper is to make evidence-based recommendations to facilitate the implementation of BRAF mutation testing and targeted therapy in patients with metastatic melanoma in the U.K. The recommendations are the result of a meeting of an expert panel and have been reviewed by melanoma specialists and representatives of the National Cancer Research Network Clinical Study Group on behalf of the wider melanoma community. This article is intended to be a starting point for practical advice and recommendations, which will no doubt be updated as we gain further experience in personalizing therapy for patients with melanoma.

Refining the diagnosis and EGFR status of non-small cell lung carcinoma in biopsy and cytologic material, using a panel of mucin staining, TTF-1, cytokeratin 5/6, and P63, and EGFR mutation analysis.

INTRODUCTION: The dichotomization of non-small cell carcinoma (NSCLC) subtype into squamous (SQCC) and adenocarcinoma (ADC) has become important in recent years and is increasingly required with regard to management. The aim of this study was to determine the utility of a panel of commercially available antibodies in refining the diagnosis on small biopsies and also to determine whether cytologic material is suitable for somatic EGFR genotyping in a prospectively analyzed series of patients undergoing investigation for suspected lung cancer. METHODS: Thirty-two consecutive cases of NSCLC were first tested using a panel comprising cytokeratin 5/6, P63, thyroid transcription factor-1, 34betaE12, and a D-PAS stain for mucin, to determine their value in refining diagnosis of NSCLC. After this test phase, two further pathologists independently reviewed the cases using a refined panel that excluded 34betaE12 because of its low specificity for SQCC, and refinement of diagnosis and concordance were assessed. Ten cases of ADC, including eight derived from cytologic samples, were sent for EGFR mutation analysis. RESULTS: There was refinement of diagnosis in 65% of cases of NSCLC to either SQCC or ADC in the test phase. This included 10 of 13 cases where cell pellets had been prepared from transbronchial needle aspirates. Validation by two further pathologists with varying expertise in lung pathology confirmed increased refinement and concordance of diagnosis. All samples were adequate for analysis, and they all showed a wild-type EGFR genotype. CONCLUSION: A panel comprising cytokeratin 5/6, P63, thyroid transcription factor-1, and a D-PAS stain for mucin increases diagnostic accuracy and agreement between pathologists when faced with refining a diagnosis of NSCLC to SQCC or ADC. These small samples, even cell pellets derived from transbronchial needle aspirates, seem to be adequate for EGFR mutation analysis.

Utilisation of Glass Reinforced Plastics as Cost Effective Alternative to Traditional Materials in Access Panel Design for Waste Water Treatment Plants

Composites are fast becoming a cost effective option when considering the design of engineering structures in a broad range of applications. If the strength to weight benefits of these material systems can be exploited and challenges in developing lower cost manufacturing methods overcome, then the advanced composite systems will play a bigger role in the diverse range of sectors outside the aerospace industry where they have been used for decades.
This paper presents physical testing results that showcase the advantages of GRP (Glass Reinforced Plastics), such as the ability to endure loading with minimal deformation. The testing involved is a cross comparison of GRP grating vs. GRP encapsulated foam core. Resulting data gained within this paper will then be coupled with design optimization (utilising model simulation) to bring forward layup alterations to meet the specified load classifications involved.