Computationally efficient calibration of WATCLASS Hydrologic models using surrogate optimization

International audienceIn this approach, exploration of the cost function space was performed with an inexpensive surrogate function, not the expensive original function. The Design and Analysis of Computer Experiments(DACE) surrogate function, which is one type of approximate models, which takes correlation function for error was employed. The results for Monte Carlo Sampling, Latin Hypercube Sampling and Design and Analysis of Computer Experiments(DACE) approximate model have been compared. The results show that DACE model has a good potential for predicting the trend of simulation results. The case study of this document was WATCLASS hydrologic model calibration on Smokey-River watershed

Low-density lipoprotein concentration in the normal left coronary artery tree

<p>Abstract</p> <p>Background</p> <p>The blood flow and transportation of molecules in the cardiovascular system plays a crucial role in the genesis and progression of atherosclerosis. This computational study elucidates the Low Density Lipoprotein (LDL) site concentration in the entire normal human 3D tree of the LCA.</p> <p>Methods</p> <p>A 3D geometry model of the normal human LCA tree is constructed. Angiographic data used for geometry construction correspond to end-diastole. The resulted model includes the LMCA, LAD, LCxA and their main branches. The numerical simulation couples the flow equations with the transport equation applying realistic boundary conditions at the wall.</p> <p>Results</p> <p>High concentration of LDL values appears at bifurcation opposite to the flow dividers in the proximal regions of the Left Coronary Artery (LCA) tree, where atherosclerosis frequently occurs. The area-averaged normalized luminal surface LDL concentrations over the entire LCA tree are, 1.0348, 1.054 and 1.23, for the low, median and high water infiltration velocities, respectively. For the high, median and low molecular diffusivities, the peak values of the normalized LDL luminal surface concentration at the LMCA bifurcation reach 1.065, 1.080 and 1.205, respectively. LCA tree walls are exposed to a cholesterolemic environment although the applied mass and flow conditions refer to normal human geometry and normal mass-flow conditions.</p> <p>Conclusion</p> <p>The relationship between WSS and luminal surface concentration of LDL indicates that LDL is elevated at locations where WSS is low. Concave sides of the LCA tree exhibit higher concentration of LDL than the convex sides. Decreased molecular diffusivity increases the LDL concentration. Increased water infiltration velocity increases the LDL concentration. The regional area of high luminal surface concentration is increased with increasing water infiltration velocity. Regions of high LDL luminal surface concentration do not necessarily co-locate to the sites of lowest WSS. The degree of elevation in luminal surface LDL concentration is mostly affected from the water infiltration velocity at the vessel wall. The paths of the velocities in proximity to the endothelium might be the most important factor for the elevated LDL concentration.</p

A phase II study of capecitabine and oxalplatin combination chemotherapy in patients with inoperable adenocarcinoma of the gall bladder or biliary tract

Background: Advanced biliary tract carcinomas are associated with a poor prognosis, and palliative chemotherapy has only modest benefit. This multi-centre phase II study was conducted to determine the efficacy of capecitabine in combination with oxaliplatin in patients with inoperable gall bladder or biliary tract cancer. Methods: This was a Phase II, non-randomised, two-stage Simon design, multi-centre study. Ethics approval was sought and obtained by the North West MREC, and then locally by the West Glasgow Hospitals Research Ethics Com mittee. Eligible patients with inoperable locally advanced or metastatic adenocarcinoma of the gall bladder or biliary tract and with adequate performance status, haematologic, renal, and hepatic function were treated with capecit abine (1000 mg/m2 po, twice daily, days 1–14) and oxaliplatin (130 mg/m2 i.v., day 1) every 3 weeks for up to six cycles. The primary objective of the study was to determine the objective tumour response rates (complete and partial). The secondary objectives included assessment of toxicity, progression-free survival, and overall survival. Results: Forty-three patients were recruited between July 2003 and December 2005. The regimen was well tolerated with no grade 3/4 neutropenia or thrombocytopenia. Grade 3/4 sensory neuropathy was observed in six patients. Two-thirds of patients received their chemotherapy without any dose delays. Overall response rate was 23.8 % (95 % CI 12.05–39.5 %). Stable disease was observed in a further 13 patients (31 %) and progressive disease observed in 12 (28.6 %) of patients. The median progression-free survival was 4.6 months (95 % CI 2.8–6.4 months; Fig. 1) and the median overall survival 7.9 months (95 % CI 5.3–10.4 months; Fig. 2). Conclusion: Capecitabine combined with oxaliplatin has a lower disease control and shorter overall survival than the combination of cisplatin with gemcitabine which has subsequently become the standard of care in this disease. How ever, capecitabine in combination with oxaliplatin does have modest activity in this disease, and can be considered as an alternative treatment option for patients in whom cisplatin and/or gemcitabine are contra-indicated

Perceptions, attitudes and training needs of primary healthcare professionals in identifying and managing frailty: a qualitative study

PURPOSE: Although frailty can be delayed or prevented by appropriate interventions, these are often not available in countries lacking formal education and infrastructure in geriatrics. The aim of this study was to: (a) explore ideas, perceptions and attitudes of primary health care (PHC) professionals towards frailty in a country where geriatrics is not recognised as a specialty; (b) explore PHC professionals' training needs in frailty; and (c) define components of a frailty educational programme in PHC. METHODS: Qualitative design, using two focus groups with PHC professionals conducted in Thessaloniki, Greece. Focus groups were audio recorded and transcribed. Data were analysed with thematic analysis. RESULTS: In total 31 PHC professionals (mean age: 46 years; gender distribution: 27 females, 4 males) participated in the study (physicians n = 17; nurses n = 12; health visitors n = 2). Four main themes were identified: (1) Perceptions and understanding of frailty; (2) Facilitators and barriers to frailty identification and management; (3) Motivation to participate in a frailty training programme; (4) Education and training. The main barriers for the identification and management of frailty were associated with the healthcare system, including duration of appointments, a focus on prescribing, and problems with staffing of allied health professionals, but also a lack of education. Training opportunities were scarce and entirely based on personal incentive. Professionals were receptive to training either face-to-face or online. A focus on learning practical skills was key. CONCLUSION: Education and training of professionals and interdisciplinary collaboration are essential and much needed for the delivery of person-centred care for people with frailty living in the community

Development of the MESH modelling system for hydrological ensemble forecasting of the Laurentian Great Lakes at the regional scale

International audienceEnvironment Canada has been developing a community environmental modelling system (Modélisation Environmentale Communautaire ? MEC), which is designed to facilitate coupling between models focusing on different components of the earth system. The ultimate objective of MEC is to use the coupled models to produce operational forecasts. MESH (MEC ? Surface and Hydrology), a configuration of MEC currently under development, is specialized for coupled land-surface and hydrological models. To determine the specific requirements for MESH, its different components were implemented on the Laurentian Great Lakes watershed, situated on the Canada-US border. This experiment showed that MESH can help us better understand the behaviour of different land-surface models, test different schemes for producing ensemble streamflow forecasts, and provide a means of sharing the data, the models and the results with collaborators and end-users. This modelling framework is at the heart of a testbed proposal for the Hydrologic Ensemble Prediction Experiment (HEPEX) which should allow us to make use of the North American Ensemble Forecasting System (NAEFS) to improve streamflow forecasts of the Great Lakes tributaries, and demonstrate how MESH can contribute to a Community Hydrologic Prediction System (CHPS)

Using the MESH modelling system for hydrological ensemble forecasting of the Laurentian Great Lakes at the regional scale

International audienceEnvironment Canada has been developing a community environmental modelling system (Modélisation Environmentale Communautaire ? MEC), which is designed to facilitate coupling between models focusing on different components of the earth system. The ultimate objective of MEC is to use the coupled models to produce operational forecasts. MESH (MEC ? Surface and Hydrology), a configuration of MEC currently under development, is specialized for coupled land-surface and hydrological models. To determine the specific requirements for MESH, its different components were implemented on the Laurentian Great Lakes watershed, situated on the Canada?U.S. border. This experiment showed that MESH can help us better understand the behaviour of different land-surface models, test different schemes for producing ensemble streamflow forecasts, and provide a means of sharing the data, the models and the results with collaborators and end-users. This modelling framework is at the heart of a testbed proposal for the Hydrologic Ensemble Prediction Experiment (HEPEX) which should allow us to make use of the North American Ensemble Forecasting System (NAEFS) to improve streamflow forecasts of the Great Lakes tributaries, and demonstrate how MESH can contribute to a Community Hydrologic Prediction System (CHPS)

The Relevance and Added Value of Geriatric Medicine (GM): Introducing GM to Non-Geriatricians

Geriatric Medicine (GM) holds a crucial role in promoting health and managing the complex medical, cognitive, social, and psychological issues of older people. However, basic principles of GM, essential for optimizing the care of older people, are commonly unknown or undermined, especially in countries where GM is still under development. This narrative review aims at providing insights into the role of GM to non-geriatrician readers and summarizing the main aspects of the added value of a geriatric approach across the spectrum of healthcare. Health practitioners of all specialties are frequently encountered with clinical conditions, common in older patients (such as cancer, hypertension, delirium, major neurocognitive and mental health disorders, malnutrition, and peri-operative complications), which could be more appropriately managed under the light of the approach of GM. The role of allied health professionals with specialized knowledge and skills in dealing with older people’s issues is essential, and a multidisciplinary team is required for the delivery of optimal care in response to the needs and aspirations of older people. Thus, countries should assure the educational background of all health care providers and the specialized health and social care services required to meet the demands of a rapidly aging society

Feasibility and impact of a short training course on frailty destined for primary health care professionals

BACKGROUND: There is an unmet need for training primary health care professionals on frailty, especially in countries where geriatrics is still emerging. PURPOSE: We aimed to evaluate the feasibility and efficacy of a training course for primary health care professionals on the detection, assessment, and management of frailty. METHODS: A single-day training course, developed and facilitated by three physicians trained in geriatrics abroad, was organized by the Aristotle University of Thessaloniki Primary Hearth Care Research Network. Primary health care professionals' attitudes, knowledge, and everyday practices regarding frailty were assessed by self-administered anonymous questionnaires (using Likert-type scales) at three time-points (before, upon completion of the training course, and 3 months afterward). RESULTS: Out of 31 participants (17 physicians, 12 nurses, 2 health visitors; 87.1% women; mean age 46.4 years), 31(100%) filled in the first, 30(97%) the second, and 25(81%) the third questionnaire. Improvements were reported in familiarization with the frailty syndrome (p = 0.041) and in self-perception of knowledge and skills to detect (p < 0.001) and manage (p < 0.001) frailty, that were also sustained 3 months afterward (p = 0.001 and p = 0.003 respectively). Improvement was also observed in the attitude that frailty is an inevitable consequence of aging (p = 0.007) and in the frequency of application of screening (but not management) strategies, 3 months following the workshop compared to baseline (p = 0.014). Participants reported less disagreement with the statement that systematic screening for frailty was unfeasible in their daily practice at 3 months compared to baseline (p = 0.006), mainly due to time restrictions. CONCLUSION: A short skill-oriented training course can significantly and sustainably improve primary health care professionals' attitudes and practices regarding frailty

Energy levels of periodic solutions of the circular 2+2 Sitnikov problem

We study a 2+2 body problem introduced in a previous paper as the circular double Sitnikov problem. Since the secondary bodies are moving on the same perpendicular line where evolve the primaries, almost every solution is a collision orbit. We extend the solutions beyond collisions with a symplectic regularization and study the set of energy surfaces that contain periodic orbits and their foliations .Comment: 20 pages, 5 figures. This is not the final version

ATLANTIS: a randomised multi-arm phase II biomarker-directed umbrella screening trial of maintenance targeted therapy after chemotherapy in patients with advanced or metastatic urothelial cancer

Background Metastatic urothelial cancer (UC) is the eighth most common cause of cancer death in the UK. Standard first-line treatment, for most patients, is cytotoxic chemotherapy. Although UC is initially sensitive to chemotherapy, relapse is almost inevitable and outcomes are poor; median overall survival is 8 months. Therefore, there is an urgent need for novel therapies to improve outcomes for this patient group. Methods ATLANTIS is a randomised phase II umbrella-design screening trial of maintenance therapy in biomarker-defined subgroups of patients with advanced UC. The primary end point is progression-free survival, and the study involves over 30 UK cancer centres. Discussion ATLANTIS is the first study in the UK to employ a precision-medicine approach to patients with UC for maintenance treatment. Agents with a positive efficacy signal will proceed to randomised phase III trials to confirm the activity of novel, biologically stratified therapies in UC. Registration ATLANTIS trial EudraCT number 2015–003249-25. ISRCTN25859465