Effectively Including Human Factors in the Design of New Facilities

Human error is a major cause of incidents in the offshore industry. For example, in the Gulf of Mexico region in 1998, 38% of all incidents were attributed to human error with an additional 9% of incidents resulting from slips, trips, and falls (MMS 2000-021, OCS Report). Human Factors, when integrated during the design of a new offshore facility, can reduce the potential for human error and the occurrence of unfortunate incidents. Quite often the implementation of Human Factors (HF) during design is disregarded because of the notion that it will add unacceptable costs. Review of the cost/benefit data contained in this paper proves that notion to be untrue. Although cost/benefit is important, it was not the primary focus of this Working Group. This paper’s focus is to develop a means or a strategy to effectively integrate the application of HF design principles into all phases of a new capital design project. This Working Group’s objective during the Second International Workshop on Human Factors in Offshore Operations was to generate discussion concerning HF integration strategies and to focus on specific implementation issues that have been shown to be successful. These include but are not limited to: · The factors critical to the success of HF integration · What HF activities should be conducted · At what stage during the various design phases should HF activities take place · HF strategies, how to decide what level of human factors engineering is required · The qualifications and responsibilities of those executing HF activitie

Effectively Including Human Factors in the Design of New Facilities

Human error is a major cause of incidents in the offshore industry. For example, in the Gulf of Mexico region in 1998, 38% of all incidents were attributed to human error with an additional 9% of incidents resulting from slips, trips, and falls (MMS 2000-021, OCS Report). Human Factors, when integrated during the design of a new offshore facility, can reduce the potential for human error and the occurrence of unfortunate incidents. Quite often the implementation of Human Factors (HF) during design is disregarded because of the notion that it will add unacceptable costs. Review of the cost/benefit data contained in this paper proves that notion to be untrue. Although cost/benefit is important, it was not the primary focus of this Working Group. This paper’s focus is to develop a means or a strategy to effectively integrate the application of HF design principles into all phases of a new capital design project. This Working Group’s objective during the Second International Workshop on Human Factors in Offshore Operations was to generate discussion concerning HF integration strategies and to focus on specific implementation issues that have been shown to be successful. These include but are not limited to: · The factors critical to the success of HF integration · What HF activities should be conducted · At what stage during the various design phases should HF activities take place · HF strategies, how to decide what level of human factors engineering is required · The qualifications and responsibilities of those executing HF activitie

Locally increased P-glycoprotein function in major depression: a PET study with [C-11]verapamil as a probe for P-glycoprotein function in the blood-brain barrier

The aetiology of depressive disorder remains unknown, although genetic susceptibility and exposure to neurotoxins are currently being discussed as possible contributors to this disorder. In normal circumstances, the brain is protected against bloodborne toxic influences by the blood-brain barrier, which includes the molecular efflux pump P-glycoprotein (P-gp) in the vessel wall of brain capillaries. We hypothesized that P-gp function in the blood-brain barrier is changed in patients with major depression. Positron emission tomography Was used to measure brain uptake of [C-11]verapamil, which is normally expelled from the brain by P-gp. Cerebral Volume of distribution (V-T) of [C-11]verapamil was used as a measure of P-gp function. Both region-of-interest (ROI) analysis and voxel analysis using statistical parametric mapping (SPM2) were performed to assess regional brain P-gp function. We found that patients with a major depressive episode, using antidepressants, compared to health), controls showed a significant decrease of [C-11]verapamil uptake in different areas throughout the brain, in particular in frontal and temporal regions. The decreased [C-11]verapamil uptake correlates with an increased function of the P-gp protein and may be related to chronic use of psychotropic drugs, Our results may explain why treatment-resistant depression can develop

The transcriptional landscape of Shh medulloblastoma

© The Author(s) 2021. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Sonic hedgehog medulloblastoma encompasses a clinically and molecularly diverse group of cancers of the developing central nervous system. Here, we use unbiased sequencing of the transcriptome across a large cohort of 250 tumors to reveal differences among molecular subtypes of the disease, and demonstrate the previously unappreciated importance of non-coding RNA transcripts. We identify alterations within the cAMP dependent pathway (GNAS, PRKAR1A) which converge on GLI2 activity and show that 18% of tumors have a genetic event that directly targets the abundance and/or stability of MYCN. Furthermore, we discover an extensive network of fusions in focally amplified regions encompassing GLI2, and several loss-of-function fusions in tumor suppressor genes PTCH1, SUFU and NCOR1. Molecular convergence on a subset of genes by nucleotide variants, copy number aberrations, and gene fusions highlight the key roles of specific pathways in the pathogenesis of Sonic hedgehog medulloblastoma and open up opportunities for therapeutic intervention.info:eu-repo/semantics/publishedVersio

Failure of human rhombic lip differentiation underlies medulloblastoma formation

Medulloblastoma (MB) comprises a group of heterogeneous paediatric embryonal neoplasms of the hindbrain with strong links to early development of the hindbrain 1–4. Mutations that activate Sonic hedgehog signalling lead to Sonic hedgehog MB in the upper rhombic lip (RL) granule cell lineage 5–8. By contrast, mutations that activate WNT signalling lead to WNT MB in the lower RL 9,10. However, little is known about the more commonly occurring group 4 (G4) MB, which is thought to arise in the unipolar brush cell lineage 3,4. Here we demonstrate that somatic mutations that cause G4 MB converge on the core binding factor alpha (CBFA) complex and mutually exclusive alterations that affect CBFA2T2, CBFA2T3, PRDM6, UTX and OTX2. CBFA2T2 is expressed early in the progenitor cells of the cerebellar RL subventricular zone in Homo sapiens, and G4 MB transcriptionally resembles these progenitors but are stalled in developmental time. Knockdown of OTX2 in model systems relieves this differentiation blockade, which allows MB cells to spontaneously proceed along normal developmental differentiation trajectories. The specific nature of the split human RL, which is destined to generate most of the neurons in the human brain, and its high level of susceptible EOMES +KI67 + unipolar brush cell progenitor cells probably predisposes our species to the development of G4 MB

Latanoprost versus timolol as first choice therapy in patients with ocular hypertension A cost-effectiveness analysis

Purpose: To determine the cost-effectiveness of ocular hypertension (OH) treatment initiated with latanoprost compared to timolol. Methods: Two strategies for OH therapy are modelled, (1) 'starting with timolol' and (2) 'starting with latanoprost'. Therapy can be maintained or changed dependent on the achieved intraocular pressure (IOP) and side-effects. Adjustments of therapy to reach a target pressure involve monotherapy, combination therapy and laser. Four drugs are used: latanoprost, timolol, brimonidine and dorzolamide. Once the adjustments of therapy are completed, lifelong follow-up with IOP-dependent conversion to glaucoma and progression to blindness are modelled. Direct medical costs are assigned. The IOP-lowering effect of drugs is based on meta-analyses and applied by Monte Carlo simulation to a hypothetical cohort of patients with OH. The characteristics of the cohort, including the initial IOP distribution, are based on data of 1000 patients. Results: The IOP decreased from 25,4 mm Hg (mean) to 16.7 (+/-0.017) mm Hg (strategy 1) and to 16.5 (+/-0.013) mm Hg (strategy 2). Costs per patient within 15 months of therapy were (sic) 367 and (sic) 469, respectively. Lifetime blindness and costs were 0.0334 years and (sic) 3 514 (strategy 1) and 0.0318 years and (sic) 4 397 (strategy 2). Incremental costs per year of vision saved for strategy (2) in comparison with strategy (1) amount to, given the uncertainties in the model, approximately (sic) 537 000. Conclusion: For saving 1 year of vision, high costs are needed when OH therapy is initiated with latanoprost compared to timolol, when the cost price of latanoprost remains high

The long-term outcomes of four alternative treatment strategies for primary open-angle glaucoma

Purpose: To evaluate the long-term effects and costs of four treatment strategies for primary open-angle glaucoma compared to usual care. Methods: Cost-effectiveness analyses with a lifelong horizon were made from a societal perspective. Data were generated with a patient-level model based on discrete event simulation. The model structure and parameter estimates were based on literature, particularly clinical studies on the natural course of glaucoma and the effect of treatment. We simulated heterogeneous cohorts of 3000 patients and explored the impact of uncertainty with sensitivity analyses. Results: The incremental cost-effectiveness ratio (ICER) of initial treatment with a prostaglandin analogue compared with a beta-blocker was (sic)12.931 per quality-adjusted life year (QALY) gained. A low initial target pressure (15 mmHg) resulted in 0.115 QALYs gained and (sic)1550 saved compared to a gradual decrease from 21 to 15 mmHg upon progression. Visual field (VF) measurements every 6 rather than 12 months lead to health gains at increased costs (ICER (sic)173 486 per QALY gained), whereas measurements every 24 months lead to health losses at reduced costs (ICER (sic)21 516 per QALY lost). All treatment strategies were dominant over 'withholding treatment'. Conclusions: From a cost-effectiveness point of view, it seems advantageous to aim for a low intraocular pressure in all glaucoma patients. The feasibility of this strategy should therefore be investigated. Additionally, the cost-effectiveness outcomes of initiating monotherapy with a prostaglandin analogue and reducing the frequency of VF testing may be acceptable