Organisational culture in airworthiness management programs: Developing a measurement model

All civil and private aircraft are required to comply with the airworthiness standards set by their national airworthiness authority and throughout their operational life must be in a condition of safe operation. Aviation accident data shows that over twenty percent of all fatal accidents in aviation are due to airworthiness issues, specifically aircraft mechanical failures. Ultimately it is the responsibility of each registered operator to ensure that their aircraft remain in a condition of safe operation, and this is done through both effective management of airworthiness activities and the effective program governance of safety outcomes. Typically, the projects within these airworthiness management programs are focused on acquiring, modifying and maintaining the aircraft as a capability supporting the business. Program governance provides the structure through which the goals and objectives of airworthiness programs are set along with the means of attaining them. Whilst the principal causes of failures in many programs can be traced to inadequate program governance, many of the failures in large scale projects can have their root causes in the organisational culture and more specifically in the organisational processes related to decision-making. This paper examines the primary theme of project and program based enterprises, and introduces a model for measuring organisational culture in airworthiness management programs using measures drawn from 211 respondents in Australian airline programs. The paper describes the theoretical perspectives applied to modifying an original model to specifically focus it on measuring the organisational culture of programs for managing airworthiness; identifying the most important factors needed to explain the relationship between the measures collected, and providing a description of the nature of these factors. The paper concludes by identifying a model that best describes the organisational culture data collected from seven airworthiness management programs

Using the Cluster Support Team and Multi-Tiered Systems of Support to Provide Wraparound Services in a Large Urban School District

In this presentation, participants will learn how a large, urban school district utilizes the Cluster Support Team model and Multi-Tiered Systems of Support to provide wraparound services to include school counselors, social workers, behavior analysts, restorative practitioners, and mental health specialists. Participants will receive an overview of support services, and review data from the district

De-escalation of tyrosine kinase inhibitor dose in patients with chronic myeloid leukaemia with stable major molecular response (DESTINY): an interim analysis of a non-randomised, phase 2 trial

BACKGROUND: Discontinuation of tyrosine kinase inhibitor (TKI) therapy is feasible for some patients with chronic myeloid leukaemia (CML) with deep molecular responses, defined as stable MR4 (BCR-ABL1/ABL1 ratio 0.1%) on two consecutive samples. The study endpoint is the proportion of patients who lose their MMR on de-escalation and regain MMR on TKI resumption. The trial was registered at https://clinicaltrials.gov/ as NCT 01804985.FINDINGS: During the 12 months of half-dose therapy, 12 patients had molecular recurrence, all of whom regained MMR within 4 months of full dose TKI resumption. Recurrence was lower in the MR4 cohort (3 of 121 evaluable patients; 2.5%, 90% CI: 0.2-4.8%) than in the MMR cohort (9 of 48 evaluable patients; 18.8%, 90% CI: 9.5-28%) (p = 0.0007), but was unrelated to prior TKI or TKI therapy duration. Many adverse events improved during the first 3 months of de-escalation, though not thereafter. Overall, de-escalation saved 46.7% from an expected TKI budget (without de-escalation) of £4,156,969.INTERPRETATION: TKI de-escalation is safe for the vast majority of patients with excellent responses to TKI therapy, and is associated with improvement in symptoms and significant financial savings. The data imply that lower TKI doses may maintain responses in these patients

Molecular Landscape and Actionable Alterations in a Genomically Guided Cancer Clinical Trial: National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH).

PURPOSE: Therapeutically actionable molecular alterations are widely distributed across cancer types. The National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial was designed to evaluate targeted therapy antitumor activity in underexplored cancer types. Tumor biopsy specimens were analyzed centrally with next-generation sequencing (NGS) in a master screening protocol. Patients with a tumor molecular alteration addressed by a targeted treatment lacking established efficacy in that tumor type were assigned to 1 of 30 treatments in parallel, single-arm, phase II subprotocols. PATIENTS AND METHODS: Tumor biopsy specimens from 5,954 patients with refractory malignancies at 1,117 accrual sites were analyzed centrally with NGS and selected immunohistochemistry in a master screening protocol. The treatment-assignment rate to treatment arms was assessed. Molecular alterations in seven tumors profiled in both NCI-MATCH trial and The Cancer Genome Atlas (TCGA) of primary tumors were compared. RESULTS: Molecular profiling was successful in 93.0% of specimens. An actionable alteration was found in 37.6%. After applying clinical and molecular exclusion criteria, 17.8% were assigned (26.4% could have been assigned if all subprotocols were available simultaneously). Eleven subprotocols reached their accrual goal as of this report. Actionability rates differed among histologies (eg, \u3e 35% for urothelial cancers and \u3c 6% for pancreatic and small-cell lung cancer). Multiple actionable or resistance-conferring tumor mutations were seen in 11.9% and 71.3% of specimens, respectively. Known resistance mutations to targeted therapies were numerically more frequent in NCI-MATCH than TCGA tumors, but not markedly so. CONCLUSION: We demonstrated feasibility of screening large numbers of patients at numerous accruing sites in a complex trial to test investigational therapies for moderately frequent molecular targets. Co-occurring resistance mutations were common and endorse investigation of combination targeted-therapy regimens

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead