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Paranjpe, Manish D., Alfred C. Chin, Ishan Paranjpe, Nicholas J. Reid, Phan Q. Duy, Jason K. Wang, Ross O'Hagan, et al. "Self-reported health without clinically measurable benefits among adult users of multivitamin and multimineral supplements: a cross-sectional study." BMJ Open 10, no. 11 (November 2020): e039119. http://dx.doi.org/10.1136/bmjopen-2020-039119.
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ObjectiveMultiple clinical trials fail to identify clinically measurable health benefits of daily multivitamin and multimineral (MVM) consumption in the general adult population. Understanding the determinants of widespread use of MVMs may guide efforts to better educate the public about effective nutritional practices. The objective of this study was to compare self-reported and clinically measurable health outcomes among MVM users and non-users in a large, nationally representative adult civilian non-institutionalised population in the USA surveyed on the use of complementary health practices.DesignCross-sectional analysis of the effect of MVM consumption on self-reported overall health and clinically measurable health outcomes.ParticipantsAdult MVM users and non-users from the 2012 National Health Interview Survey (n=21 603).Primary and secondary outcome measuresFive psychological, physical, and functional health outcomes: (1) self-rated health status, (2) needing help with routine needs, (3) history of 10 chronic diseases, (4) presence of 19 health conditions in the past 12 months, and (5) Kessler 6-Item (K6) Psychological Distress Scale to measure non-specific psychological distress in the past month.ResultsAmong 4933 adult MVM users and 16 670 adult non-users, MVM users self-reported 30% better overall health than non-users (adjusted OR 1.31; 95% CI 1.17 to 1.46; false discovery rate adjusted p<0.001). There were no differences between MVM users and non-users in history of 10 chronic diseases, number of present health conditions, severity of current psychological distress on the K6 Scale and rates of needing help with daily activities. No effect modification was observed after stratification by sex, education, and race.ConclusionsMVM users self-reported better overall health despite no apparent differences in clinically measurable health outcomes. These results suggest that widespread use of multivitamins in adults may be a result of individuals’ positive expectation that multivitamin use leads to better health outcomes or a self-selection bias in which MVM users intrinsically harbour more positive views regarding their health.
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Kawooya, Michael G., George Pariyo, Elsie K. Malwadde, Rosemary Byanyima, and Harrient Kisembo. "Assessing the Diagnostic Imaging needs for Five Selected Hospitals in Uganda." Journal of Clinical Imaging Science 1 (November 19, 2011): 53. http://dx.doi.org/10.4103/2156-7514.90035.
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Introduction: Uganda has limited health resources. It is important to measure the need for imaging in order to set policy and plan for imaging services. Objectives: The first specific objective was to develop and apply four imaging needs indices on a case study basis, in five selected Ugandan hospitals. The indices were: Imaging Load (IL), Imaging Burden (IB), Type Specific Imaging Burden (TSIB), and Disease Specific Imaging Burden (DSIB). The second objective was to explore the perceptions of the patient, referring clinician, and radiologist regarding the values, meaning, and objective of imaging in patient care. Materials and Methods: This was a cross-sectional survey employing triangulation methodology, conducted in 5 Ugandan hospitals over a period of 3 years during 2005 - 2008. The subjects were divided into four clusters: Obstetrics and gynecology (obs/gynae), surgery, internal medicine, and pediatrics. For the quantitative component of the study, data from case notes was used to calculate the indices. The qualitative component explored the non-measurable aspects of imaging needs from the clinician's, radiologist's, and patient's perspective. Results: A total of 1961 patient case notes were studied. The IB was 460 per 1000 hospital patients per year. The highest TSIB was for ultrasound at 232 per 1000 hospital patients per year, followed by 191 patients for general X-ray. The majority of the patients interviewed had special desires, expectations, and misconceptions. Conclusions: There is a high IB of 460 per thousand patient populations per year, mainly due to ultrasound. The majority of the patients have perceptions, misconceptions, beliefs, and values which influence the need for imaging. There is a need to address the medical and non-tangible imaging needs of the patient and to counteract imaging-related misconceptions and over-expectations. Public awareness of the value, capabilities, limitations, and adverse effects of various imaging modalities need to be addressed to ensure that the patients make informed imaging choices and readily avail themselves of interventions in situations when imaging is crucial, for example in suspected high-risk pregnancy.
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Silva Oliveira, Gustavo, Philipe Ricardo Casemiro Soares, and Jean Alberto Sampietro. "QUALITY FUNCTION DEPLOYMENT (QFD) APPLIED TO THE VARIABLES THAT INFLUENCE QUALITY COSTS IN MECHANIZED FOREST HARVEST OPERATIONS." FLORESTA 50, no. 4 (September 29, 2020): 1717. http://dx.doi.org/10.5380/rf.v50i4.60137.
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Globalization and client demands result in the need for investments for the survival of the companies. Forest harvest represents the highest costs and losses of wood production. Quality function deployment (QFD) is recommended to achieve quality by detecting customer needs. Thus, this study aimed to determine the variables that influence quality costs in the mechanized harvest to reach the quality control of forest activity. The research was developed in a company located in the State of Santa Catarina, Brazil. The variables that influence quality costs in four categories (evaluation, prevention, internal and external flaws) were identified. The QFD method was used to translate the needs of internal and external customers (critical success factors) of mechanized harvesting activities into measurable technical characteristics (variables that influence quality costs), determining the weight for each relationship and, consequently, the balance of the categories, besides the correlations of the variables evaluated as strong, medium, weak, and non-existent. Among the 29 variables identified, 18 consisted of evaluation and prevention, representing the relative weights of 37.17% and 26.49%, respectively, and 11 represented internal and external flaws, with values of 26.57% and 9.73%, respectively. The correlation matrix found 334 correlation of the 406 cells: 195 (58%) strong, 86 (26%) medium, and 53 (16%) weak. In conclusion, the company must improve process quality by investing in evaluation and prevention aimed at reducing non-conformities and expansion of revenues.
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Germuth, Amy A. "Professional Development that Changes Teaching and Improves Learning." Journal of Interdisciplinary Teacher Leadership 1, no. 3 (December 1, 2018): 77–90. http://dx.doi.org/10.46767/kfp.2016-0025.
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Each year school districts invest financial resources in professional development for their educators. Beyond the cost, educators spend countless hours in workshops, training, webinars, and other learning environments intended to enhance and deepen their knowledge and skills to increase student success. Too often the return on this investment is minimal in learning transfer for educators or measurable academic gains for students and maximum in participant dissatisfaction. Substantial research in effective professional development models exists. When applied to professional development, measurable change in the learning process occurs. In 2015 WakeEd Partnership and Wake County Public School System (WCPSS), North Carolina’s largest school system, applied that research to the design of an engaging, results-oriented professional development opportunity for elementary and secondary educators – SummerSTEM. WakeEd Partnership is an education non-profit (501c3) that exists to inform, mobilize and engage the business community in support of strong public schools in Wake County. During its 35-year history, WakeEd has differentiated itself as an organization dedicated to supporting educators through professional development and resources. SummerSTEM is a hands-on professional development experience that addresses the needs of educators — adult learners — and brings real-world lessons to the classroom.
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Sarbunan, Thobias. "HOW FAR YOU KNOW ABOUT THE CURRENTS RESEARCH METHODOLOGIES IN ENGLISH FOR SPECIFIC PURPOSES (SO BETTER THAN TO UPDATE)." Academy of Education Journal 12, no. 2 (July 1, 2021): 190–204. http://dx.doi.org/10.47200/aoej.v12i2.573.
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Interestingly, the development of science needs, related to the ESP is most reliant on improvement every time. In the other hand, all grassroots, whether learners, teachers, educators or decision-makers; must work together to ensure the feasible continuation of the ESP education system. Moreover, science never sleeps at the heart of the empiric world; this process also takes place in the domain of the ESP. The complexity of the science realm that is intended to be (if, how, when, how, when, and what) the goal of improving the ESP in a sustainable process. Consequently, the debate on research and development must potentially lead to educational and non-educational concerns. In the field of education, it is definitely closely connected to all guiding processes in the growth of ESP research. Furthermore, the expected phase of the research and progress in the field of education must occur simultaneously unless the curriculum, which serves as the foundation for the educational process, intends to work consistently and in a measurable manner; if it is also tailored to the needs of global development. The expected needs are verbal and non-verbal communication abilities, including speaking, writing, listening and reading skills. This skill is dependent on realistic knowledge about the use of English for specific purposes. Whereas in the non-educational sphere, ESP plays a significant impacts on human development and mobilization, both intentionally and unintentionally, through individuals-in pairs-or groups: which definitely has the purpose. Essentially, however, the design process of the ESP study must be consistent with global needs in order to meet the objective of using standardized and comprehensive English in line with the position of the occasions.
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Iland, Emily D., Ivor Weiner, and Wendy W. Murawski. "Obstacles Faced by Latina Mothers of Children with Autism." Californian Journal of Health Promotion 10, SI-Latino (December 1, 2012): 25–36. http://dx.doi.org/10.32398/cjhp.v10isi-latino.1480.
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The CDC’s most recent autism prevalence estimates document the continued trend of higher prevalence among non-Hispanic white children compared to Hispanic children. The disproportionate underrepresentation of Latino children in the health, education and service systems is measurable, disadvantaging the child and family. This quantitative study identifies support needs and obstacles experienced by 96 Latina mothers of children with autism, active in Spanish-language parent groups in California. Study measures included the Family Needs Survey and the Caring for My Child Survey. To determine the significance of the results on the Family Needs Survey, an item-by-item chi-square analysis compared results to those of to a similar population from a different study that used the same measure. A high proportion of mothers reported substantial levels of unmet needs in their role as primary caregiver using the Family Needs Survey: all 35 survey items were unmet for at least 50% of mothers; 28 items were common needs. The level and number of unmet needs of mothers in the present study in areas such as social support and care services were significantly greater than the comparison group. On the Caring for My Child Survey, mothers identified multiple barriers personally encountered in obtaining assistance for their children including psychosocial, economic, political, and healthcare factors. Findings are relevant to improve access for Latinos in the health, education and service systems, and to establish a baseline for comparison.
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Knight, Peter Titcomb. "Sufficiency, Sustainability, and Innovation Media Moonshot." International Journal of Social Ecology and Sustainable Development 11, no. 2 (April 2020): 67–79. http://dx.doi.org/10.4018/ijsesd.2020040105.
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This article introduces the role of innovation and exponential technologies to eliminate shortfalls in access to basic needs at a global level while achieving sustainability in four dimensions: economic, social, political and ecological. Next the article reviews the literature concerning the role of films and TV programs on influencing public opinion and producing changes in economic, social, and political outcomes. Several films and TV programs that have achieved this are presented, with documentation of their successes. Then a “media moonshot” is proposed to help develop support for public policies to accelerate progress toward sufficiency and sustainability through innovation. This would be achieved by helping finance a tenfold increase in production of films and TV programs in this field. Various fiction and non-fiction formats would be used. The goal proposed is to reach an audience of at least one billion people with measurable impacts on public opinion and government policies. Several examples of possible films and TV programs are presented.
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Vîlceanu, Titela. "Developing Evaluation Skills with Legal Translation Trainees." Acta Universitatis Sapientiae, Philologica 7, no. 3 (December 1, 2015): 5–13. http://dx.doi.org/10.1515/ausp-2015-0050.
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Abstract Axiomatically, translation is twofold: an activity/process (more accurately designated by the term translating) and a product (the term translation can be restricted to the product). It seems that the product dimension has gained increased importance, being the most visible part of translation as market-driven, design-oriented, precise and measurable - complying with specifications. Translation engenders a sequence: identification of text type and of end users’ needs (experts or non-experts in the field), evaluation of the complexity of the source text via global reading, followed by a close reading of its parts, the translating of the document, the translator’s checking of final version, editing and proofreading. The translator’s choices are accountable in point of cost-effectiveness (efficiency) and effectiveness. Therefore, the legal translator should master the methodological toolkit, conceptual frame and related terminology, and adopt an inward-looking perspective (intuition, subjectivity, ingrained habits, insights deriving from his/her expertise and experience) alongside an outward-looking one (working against objective criteria, standards of quality, benchmarks, etc).
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Munifah, Munifah, Rohmatul Fahmi Fajrin, and Fartika Ifriqia. "Implementation of Strengthening Character Education in Realizing Islamic Values in SMPN 01 Kediri." Didaktika Religia 7, no. 1 (June 2, 2019): 45–69. http://dx.doi.org/10.30762/didaktika.v7i1.1551.
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This article aims to find out the planning, implementation and evaluation of Strengthening Character Education (SCE) in SMPN 01 Kediri in realizing Islamic values. Islamic education is an effort to actualize the attributes of perfection that have been bestowed by Allah to humans. Strengthening Character Education (SCE) is one way to actualize Islamic values through various activities, intra-curricular, extra-curricular, and non-curricular. This article was written based on the results of a qualitative case study. This article concludes that the implementation of SCE in SMPN 01 Kota in realizing Islamic values, in general, has already been carried out and several aspects need to be improved. Planning for SCE activities in realizing Islamic values needs to be developed in several aspects, namely: (1) there is a need to develop SCE objective indicators, (2) additional activities need to be developed to develop the other three characters in SCE, in order to balance the characters in SCE such as integrity, mutual cooperation, and independence, and (3) SCE activities need to be developed through co-curricular activities, bearing in mind that SCE activities are still focused into extra-curricular activities. The implementation of SCE activities in realizing Islamic values requires the role of parents because they are the first education and as supervisors for their children outside of school. It is also found that evaluating SCE activities in realizing Islamic values had not used measurable appraisal instruments, but direct observation instead.
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Kumar, Shaji, Morie A. Gertz, Suzanne R. Hayman, Martha Q. Lacy, Angela Dispenzieri, Steve R. Zeldenrust, John A. Lust, et al. "Use of the Serum Free Light Chain Assay in Assessment of Response to Therapy in Multiple Myeloma: Validation of Recently Proposed Response Criteria in a Prospective Clinical Trial of Lenalidomide Plus Dexamethasone for Newly Diagnosed Multiple Myeloma." Blood 106, no. 11 (November 16, 2005): 3479. http://dx.doi.org/10.1182/blood.v106.11.3479.3479.
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Abstract Background: The serum free light chain (FLC) assay is increasingly used to monitor patients (pts) with oligo-secretory or non-secretory multiple myeloma (MM) and pts with primary amyloidosis lacking measurable monoclonal protein in the serum or urine. Criteria to use this assay to assess response to therapy have recently been proposed (Rajkumar SV, Kyle RA. Best Pr Clin Haematol2005;18:585–601) but have not been validated. The goal of this study was to validate the response criteria for the FLC assay in a prospective trial of lenalidomide plus dexamethasone in newly diagnosed MM. Methods: 34 pts were enrolled in the trial; 27 pts who had serial FLC assessments were studied. FLC estimation was carried out using the serum FLC assay (FreeliteH, The Binding Site Limited, UK) performed on a Dade-Behring Nephelometer. Pts with κ /λ FLC ratio <0.26 were defined as having monoclonal λ FLC and those with ratios >1.65 as having a monoclonal κ FLC. The monoclonal light chain isotype was considered the “involved” FLC isotype, and the opposite light chain type as the “uninvolved” FLC type. Partial response (PR) required an abnormal baseline FLC ratio and any one of the two following criteria: 1) a 50% decrease in the level of the involved FLC plus a 50% decrease (or normalization) in the ratio of involved/uninvolved FLC or 2) 50% decrease in the difference between involved and uninvolved FLC levels. Complete response (CR) required normalization of FLC ratio and negative serum and urine immunofixation. Response at 4 months or earlier by the Bladé criteria was compared to FLC response criteria from the same evaluation. Results: Three pts had normal FLC levels and ratio and were not included in the analysis. 23 of the remaining 24 achieved a PR or better by Bladé criteria. A 50% decrease in the level of the involved FLC plus a 50% decrease (or normalization) in the ratio of involved/uninvolved FLC correctly classified 20 of the 22 responding pts (sensitivity 91%); 2 pts could not be evaluated since baseline FLC ratio could not be calculated. On the other hand, a 50% decrease in the mathematical difference between involved and uninvolved FLC levels correctly classified all 24 responding pts (sensitivity 100%). The one non-responding pt by Blade criteria was correctly classified by both FLC criteria. All pts were correctly classified by both criteria when only those with a baseline “involved” FLC level of at least ≥10mg/dL (≥100mg/L) were considered (15 pts). Conclusions: This study demonstrates that the serum FLC assay can be used to assess response to therapy. A 50% decrease in the difference between “involved” and “uninvolved” FLC levels will suffice as FLC criteria for PR, eliminating the need for the alternative criteria based on the involved FLC level and the ratio. We recommend that this FLC response criteria be used only in pts not having measurable levels of serum and /or urine M protein.The FLC response criteria will now enable most patients with oligo-secretory and non-secretory MM to enter trials for which they are currently ineligible due to “lack of measurable serum or urine M protein.” This study is limited by the lack of adequate non-responders to calculate specificity and lack pts who progressed to validate progression criteria and needs further validation.
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Chauhan, Pradeep S., and Geetanjali Singh. "Economic Efficiency Measurement of Power Sector Reforms in Haryana Using DEA." Indian Economic Journal 68, no. 2 (June 2020): 141–71. http://dx.doi.org/10.1177/0019466220976022.
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Haryana power sector reforms were initiated as a part of the overall power sector reform process initiated in the country under the supervision of the World Bank. Haryana became the second state in the country that implemented the restructuring process at the state level after Orissa. Enhancing efficiency, productivity and quality are the goals behind these reforms. This article attempts to measure the economic efficiency of the power sector reforms in Haryana. A non-parametric technique—data envelopment analysis (DEA)—is used to measure the economic efficiency in the pre- and post-reform period of power sector reforms. Also, the specification of input and output has been carried out and an input-oriented approach has been selected. the result reveals that the power sector reforms have significantly improved efficiency in input utilisation, but as far as scale efficiency is concerned, the power sector has measurable failures on this front. The power sector in Haryana still operates with inappropriate size of scale. Therefore, a well-calibrated and robust permanent policy needs to be formulated to achieve the objectives of the power sector reforms.
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Bown, Michael, and Mark D. Hutchings. "Code Compliance and Functionality of Low-Energy Automatic Doors at Universities." Journal of Facility Management Education and Research 2, no. 2 (January 1, 2018): 83–89. http://dx.doi.org/10.22361/jfmer/00073.
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ABSTRACT Facility managers at universities should be concerned about the safety of those using low-energy automatic doors in campus buildings, particularly disabled people. People in wheelchairs have increased risk of injury from automatic door malfunction due to their limited mobility. Beyond basic functionality – opening and closing automatically – these doors must also adhere to certain government standards which are measurable. Facility management departments that operate under staffing constraints might not have enough resources to regularly verify that their doors are functioning within the government standard – especially at universities with numerous doors. In such cases, facility managers often rely on reactive feedback (i.e., feedback from users) to know when a door needs attention. Generally, such reactive feedback provides information on whether the doors are functioning, not on whether they are meeting government standards. This study 1) determined whether low-energy automatic doors at universities in the Intermountain West were properly working and were code compliant; 2) developed a simple methodology for measuring code compliance of low-energy automatic doors (opening/closing times and forces) and determining the time needed for facility managers to perform the tests. The study showed that it does not require much effort to measure the “functionality”, meaning the doors open and close properly and are code compliant. This can reduce or eliminate the need for facility managers to rely on inconsistent reactive feedback. The researchers tested 800 doors at seven large universities in the Intermountain West and found that 37 percent of the doors tested were non-functional and/or non-code-compliant. About two minutes were required to test each door. This large number of non-functioning doors should motivate facility managers to proactively test low-energy automatic doors and develop preventive maintenance plans for them.
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Kubinski, W. R., C. Carasco, D. Kikola, C. Mathonat, D. Ricard, D. Tefelski, and H. Tietze-Jaensch. "Calorimetric Non-Destructive Assay of Large Volume and Heterogeneous Radioactive Waste Drums." EPJ Web of Conferences 225 (2020): 06003. http://dx.doi.org/10.1051/epjconf/202022506003.
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The EU-CHANCE project aims at the issue of the characterization of conditioned radioactive waste (CRW) and one objective of CHANCE is to focus on: Calorimetry as a comprising non-destructive technique to reduce uncertainties on the inventory of radwaste containing shielded and hidden material difficult to be measured by other means. A MCNP6-based numerical study comprising the particle flux out of a 200L mock-up drum in a Large Volume Calorimeter (LVC) currently manufactured by KEP Nuclear (France) will be presented and discussed. For the analyses, the particle flux and energy deposition in each layer of the calorimeter were determined. The results yield that a significant fraction of the radiation would leave the system and not contribute to the measurable heat deposition. The expected energy deposition is obtained and cumulated for each layer over the whole energy range revealing the fraction of particles actually escaping the LVC calorimeter. While this escape fraction needs and can be determined, the LVC is a very suitable apparatus for the anticipated experiments on large and heterogeneous waste drums that possibly contain deeply buried beta-emitters (e.g. Sr/Y-90) or shielded alpha-sources hidden inside the drum with a significant level of gamma and neutron radiation background radiation. The high-energy part of this gamma and neutron flux may even reach the reference chamber of the calorimeter and deposit some energy there, compromising the calibration and may cause a double-bias.
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., Abdussattar, and Malik Itrat. "Risk factor profile for non-communicable diseases: findings of a STEPS survey from urban settlement of Bangalore." International Journal Of Community Medicine And Public Health 6, no. 1 (December 24, 2018): 234. http://dx.doi.org/10.18203/2394-6040.ijcmph20185249.
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Background: Increasing burden of non-communicable diseases (NCDs) across the globe is largely due to the rise in prevalence of various risk factors. These risk factors are measurable and largely modifiable. Quantifying the present levels of risk factors exposure in a community is helpful in predicting the future risk and driving the public health policy for prevention and control of NCDs. Keeping this in mind, present study was planned to estimate the prevalence of NCDs risk factors in an urban settlement of Bangalore.Methods: A community based cross-sectional survey was done with 600 individuals aged 15-64 years in Hegganahalli locality of Bangalore city from April to October 2017. Systematic random sampling technique was applied to obtain the desired sample size. Information on NCD risk factors was collected by using STEPS questionnaire.Results: Tobacco and alcohol consumption was observed in 27.2% and 11.8% of respondents respectively. Low level of physical activity was recorded among 14.8% and inadequate consumption of fruit and vegetable was observed among all the respondents. Prevalence of general and central obesity in the study population was found to be 30.7% and 12.8% respectively. Hypertension was prevalent among 35.5% respondents.Conclusions: High prevalence of NCD risk factors was observed among the study population that needs to be addressed through a comprehensive approach with due emphasis on preventive care in order to make ‘healthy living’ a social norm.
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Wang, Enli, and Chris J. Smith. "Modelling the growth and water uptake function of plant root systems: a review." Australian Journal of Agricultural Research 55, no. 5 (2004): 501. http://dx.doi.org/10.1071/ar03201.
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Crop models have been intensively used as a tool to analyse the performance of cropping systems under variable climate in terms of productivity, profitability, and off-site impact. The importance of modelling the function of plant roots in water and nutrient uptake from the soil is becoming increasing clear with the expanding application areas of crop models. This paper reviews the approaches and assumptions used in growth and uptake modelling of plant roots, and how the responses of plant root system to internal and external factors are captured in the widely used crop models. Most modelling approaches are based on one of the following assumptions: (i) that plant roots are uniformly distributed in homogenous soil layers and all roots have the same ability for uptake, or (ii) that plant root length is always sufficient for resource uptake in rooted soil layers. In structured soils, an overestimation of water uptake is likely to be expected. Further studies on root growth, distribution, and function in structured soils will require quantification of soil structures and root distribution patterns; and for non-uniformly distributed plant populations, spatial distribution of plant roots and non-uniform uptake need to be modelled. Root architecture modelling may help to address such issues. However, in order for the model to be useful at the field production level, simplified approaches that require easily measurable inputs need to be developed. Some examples are given. The oversimplification of root response to soil drying and hardness is likely to lead to overestimation of root growth and water uptake in dense soils. A soil strength factor needs to be incorporated so that the improved model can help evaluate the effect of subsoil compaction on production and resource use. Responses of root growth and uptake to soil salinity, boron toxicity, and extreme pH need to be further investigated if models are to be used for evaluation of crop performance in such environments. Effect of waterlogging also needs to be added for use of the model on heavy clay soils under irrigation or concentrated rainfall. There is an urgent need for joint efforts of crop physiologists, agronomists, breeders, and soil scientists to integrate interdisciplinary knowledge and to collect data that better describe the crop root system and its growth and uptake ability, to quantify plant process level responses, and for better soil quantification. Such knowledge and data are essential for improvement of model performance and successful applications.
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Laswati, Dyah Titin. "MASALAH GIZI DAN PERAN GIZI SEIMBANG." AGROTECH : JURNAL ILMIAH TEKNOLOGI PERTANIAN 2, no. 1 (February 5, 2019): 69–73. http://dx.doi.org/10.37631/agrotech.v2i1.12.
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Good nutrition will be consistent with good health. In the clinical symptoms of malnutrition is the body's growth and not normal development. Nutritional status was the final result of the various factors that may relate to one anothers. Therefore, understanding how the nutrient problems should be the basis for a strategy for the prevention and mitigation. The nutritional status is directly influenced by two things, the adequacy of nutrient intake to meet the needs of the body and the infection status of a person, mutually influential, so fixing one of them is not going to fix the state of the other. The guidelines of balanced nutrition was the best solution in Indonesia visualized in Tumpeng of balanced nutrition. Data of nutritional health status and nutrition-related non-communicable diseases of data obtained from the Health Research by the Ministry of Health, 2010 and micronutrient status data, especially iron deficiency anemia status. The agreement of the World Food Conference in Rome in 1992 set of recommendations to all countries, particularly developing countries to replace the slogan-based "Basic Four" to "Nutrition Guide for Balanced Diet". This emphasis is based on the fact that developing countries have to face the double burden of nutrition problems (malnutrition and over nutrition). Principle slogan "Nutrition Guide for Balanced Diet": consumption daily diet should contain nutrients in the type and amount (portion) that fits the needs of each individual or age group. Consumption of food with this pattern should pay attention to four basic principles, namely: Diversity of food; Regular physical activity and measurable; personal and environmental hygiene are maintained; and monitor or maintain weight is always ideal.
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Di Cesare, Federica, Petra Cagnardi, Roberto Villa, Vanessa Rabbogliatti, Lorena Lucatello, Francesca Capolongo, Daniela Gioeni, Michele Capasso, William Magnone, and Giuliano Ravasio. "Dexmedetomidine and ketamine simultaneous administration in tigers (Panthera tigris): pharmacokinetics and clinical effects." Veterinary Record Open 7, no. 1 (November 2020): e000412. http://dx.doi.org/10.1136/vetreco-2020-000412.
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BackgroundThe study determines the pharmacokinetic profiles of dexmedetomidine (DEX), ketamine (KET) and its active metabolite, norketamine (NORKET), after simultaneous administration. Moreover, the study evaluates the sedative effects of this protocol, its influence on the main physiological variables and the occurrence of adverse effects.MethodsEighteen captive tigers were initially administered with a mixture of DEX (10 µg/kg) and KET (2 mg/kg) by remote intramuscular injection. In case of individual and specific needs, the protocol was modified and tigers could receive general anaesthesia, propofol or additional doses of DEX and KET.ResultsBased on the immobilisation protocol, nine animals were assigned to the standard protocol group and the other nine to the non-standard protocol group. Higher area under the first moment curve (AUMC0-last) and longer mean residence time (MRT0-last) (P<0.05) were observed in the non-standard protocol group for DEX, KET and NORKET, and higher area under the concentration-time curve from administration to the last measurable concentration (AUC0-last) only for KET. The KET metabolisation rate was similar (P=0.296) between groups. No differences between groups were detected in terms of stages of sedation and recoveries. All physiological variables remained within normality ranges during the whole observation period. During the hospitalisation period, no severe adverse reactions and signs of resedation were observed.ConclusionThe simultaneous administration of 10 µg/kg of DEX and 2 mg/kg of KET can be considered an effective protocol for chemical immobilisation of captive tigers, along with dosage adjusments or when other drugs are needed.
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Lupichuk, Sasha M., Cindy Railton, Jenny J. Ko, Jennifer McCormick, Lihong Zhong, Anil Abraham Joy, Barbara Walley, and Janine Giese-Davis. "Assessing the need for a nurse-led breast cancer telephone follow-up clinic in Alberta, Canada." Journal of Clinical Oncology 31, no. 26_suppl (September 10, 2013): 111. http://dx.doi.org/10.1200/jco.2013.31.26_suppl.111.
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111 Background: Routine follow-up of breast cancer (BC) patients is largely transferred to primary care due to limited tertiary care resources and evidence supporting the acceptability and safety of this approach. It is unknown how BC survivors are faring in the community with treatment and surveillance goals, and if there is an unmet need for access to specialist care. Objectives of this cross-sectional study of BC survivors were to examine: concordance with endocrine therapy and follow-up recommendations; perceived need for help with achieving these recommendations; and, perceived need for a telephone follow-up clinic. Methods: Eligible participants were women with stage I-III BC diagnosed June 2006-September 2009 who had been seen in consultation at a tertiary cancer centre (TCC) in Alberta, Canada. 960 potentially eligible women were invited to participate via mail-out from the Alberta Cancer Registry. Consenting participants completed a structured telephone interview. Further patient, disease, endocrine therapy and surveillance data were obtained from the electronic chart and pharmacy databases. Results: 240 participants completed the telephone interview. 68.8% had been discharged from a TCC. 87.1% reported having had a clinical breast examination, and 97.1% with remaining breast tissue reported having had a surveillance mammogram within the past year. Concordance with endocrine therapy varied between pharmacy dispensing records (95.4%) versus self-report (82.0%). Top participant-identified gaps in post-treatment services were: side effect management, achieving body weight and physical activity goals, psychosocial health, and sexual health. 71.7% of participants reported that they would have used a telephone follow-up clinic. Factors associated with telephone follow-up clinic use included younger age, no endocrine therapy, fatigue, and non-urban residence. Conclusions: Concordance with measurable follow-up goals (exam, mammography, endocrine therapy) was better than expected. Despite this, interest in a nurse-led BC telephone follow-up clinic was high. Perceived needs included management of symptoms plus support for life-style behavior change.
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Anmala, Jagadeesh, and Turuganti Venkateshwarlu. "Statistical assessment and neural network modeling of stream water quality observations of Green River watershed, KY, USA." Water Supply 19, no. 6 (April 2, 2019): 1831–40. http://dx.doi.org/10.2166/ws.2019.058.
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Abstract The measurement and statistical modeling of water quality data are essential to developing a region-based stream-wise database that would be of great use to the EPA's needs. Such a database would also be useful in bio-assessment and in the modeling of processes that are related to riparian vegetation surrounding a water body such as a stream network. With the help of easily measurable data, it would be easier to come up with database-intensive numerical and computer models that explain the stream water quality distribution and biological integrity and predict stream water quality patterns. Statistical assessments of nutrients, stream water metallic and non-metallic pollutants, organic matter, and biological species data are needed to accurately describe the pollutant effects, to quantify health hazards, and in the modeling of water quality and its risk assessment. The study details the results of statistical nonlinear regression and artificial neural network models for Upper Green River watershed, Kentucky, USA. The neural network models predicted the stream water quality parameters with more accuracy than the nonlinear regression models in both training and testing phases. For example, neural network models of pH, conductivity, salinity, total dissolved solids, and dissolved oxygen gave an R2 coefficient close to 1.0 in the testing phase, while the nonlinear regression models resulted in less than 0.6. For other parameters also, neural networks showed better generalization compared with nonlinear regression models.
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Carra, Martina, Nicoletta Levi, Giulia Sgarbi, and Chiara Testoni. "From community participation to co-design: “Quartiere bene comune” case study." Journal of Place Management and Development 11, no. 2 (June 4, 2018): 242–58. http://dx.doi.org/10.1108/jpmd-06-2017-0046.
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Purpose This paper aims to contribute to research in the field of social innovation and participatory policies through the analysis of the experimental “Quartiere bene comune” project implemented by Reggio Emilia municipality. The paper focuses on the planning strategies, the operational co-design methodologies and the programming of the used processes. Design/methodology/approach Firstly, the paper reviews the regulatory instruments and previous participatory policies implemented in Italy. Secondly, it describes the approaches and methodologies used in the context of participatory policies, through strategic planning and according to bottom-up governance models. Findings The study assesses the quality of the non-standardized solutions which were adopted, both in terms of community daily needs and of management of public space. Such assessment relies on a system of measurable numerical indicators, to the goals established within the pre-agreements between public administration and community and to the ensuing consistency with the indicators provided for in the planning and executive management plan of the public body. Research limitations/implications This paper proposes a new model for the evaluation of public action, capable of highlighting the relation between assumptions, operative processes, results and impacts achieved. The study is limited to the case of seven sample neighbourhoods of a single city, in which the Citizen Agreement cycle has been completed. Originality/value The study contributes to defining the framework of participatory practices in terms of active citizenship and organizational/social innovation and proposes a new methodology of impact assessment.
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Gaižutytė-Filipavičienė, Žilvinė. "From Visuality to Visibility: Regime, Capital, Media." Art History & Criticism 16, no. 1 (December 1, 2020): 125–31. http://dx.doi.org/10.2478/mik-2020-0009.
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SummaryVisibility is a capacity to be seen by others directly or through images and can be defined as a total social fact, which includes different domains of collective life. As Italian sociologist Andrea Mubi Brighenti argues, visibility is a form of “visuality at large” and the visible entails more than the visual, more than the sensorially perceptible, which becomes clear when we consider the fact that the visual itself needs to be visibilised, and examine the ways in which this happens. In the last decades visibility in a social sphere and media was largely “capitalised”. According to French sociologist Nathalie Heinich, the visibility capitalis firmly entrenched within Western society, culture and media. Non-material capital of visibility differs from other non-material symbolical or cultural capitals in Bourdieusian sense. This new phenomenon includes all features of classical material capital. The capital of visibility is measurable, accumulated, transmissible, earning interest and convertible. It can be measured by number of fans, showing results in Google search, number of views in YouTube, number of followers in social media Instagram, Facebook or number of images in other mass media.The cult of celebrity, the aspiration for visibility, and widespread practices of seeing within contemporary visual culture touched on many important social, political, cultural and intellectual spheres. Celebrity culture that arose out of the cinema industry underwent significant transformations, penetrated into existing social structures, fields and institutions. Visibility deeply changes cultural and intellectual life, influences our values and attitudes. The regime of visibility transforms social stratification by creating celebrities as a new social category called media elite. These persons are isolated from their original environment and placed in a context with its own logic and rules. These issues will be analysed using examples from the sphere of creative and cultural industries.
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Dimaano, I. "Effort in reducing unaccountable water and economic consideration." Water Practice and Technology 10, no. 1 (March 1, 2015): 50–58. http://dx.doi.org/10.2166/wpt.2015.007.
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In 2007, Maynilad Water Services, Inc. (Maynilad), the private water and wastewater service provider of the West Zone of Metro-Manila (Philippines), had an enormous challenge ahead: to achieve 100% service coverage in the coming few years with basically no additional water resources; to connect an additional 3 million people still without access to piped water; and to improve the service level to the existing customers. The only way to meet this demand is to reduce water losses from its deteriorated pipe network. Water balance made in that year showed significant total non-revenue water of 1,500 million liters per day which is equivalent to 66% of the total system input volume. Maynilad recognized that to be financially viable, it needs to address the non-revenue water problem. Thus, the Central NRW team was immediately created in 2008 and was tasked to lead Maynilad's ambitious NRW reduction and management program, which is considered one of the largest NRW projects in the world in terms of amount of water losses and the scope and magnitude of works involved to bring down the high level of NRW. Maynilad's NRW program involves breaking up the whole network into hydraulically isolated and measurable district metered areas (DMA); monitoring and diagnosing each DMA; developing well-trained and fully equipped leak detection teams to find surfacing and non-surfacing leaks; active leakage control; pressure management; selective pipe replacement/rehabilitation; closing of illegal connections and decommissioning of old distribution pipes; integrated meter management; and a sustained capacity building of NRW teams. By the end of 2013, 6 years after implementing the NRW program, Maynilad was able to recover more than 700 MLD and managed to bring down the NRW level to 39%. The water that was saved in turn was used to supply additional 400,000 new customers in the expansion areas and generally improved the level of service of the existing customers by providing higher water pressure and longer water availability. These translated to an increase in billed volume by 56 and 107% increase in total revenues for the company.
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Nel, Yvette M., and Gregory Jonsson. "Attendance at an outpatient follow-up clinic by HIV-positive psychiatric patients initiated on ART as inpatients." South African Journal of Psychiatry 21, no. 3 (August 1, 2015): 5. http://dx.doi.org/10.4102/sajpsychiatry.v21i3.695.
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<p><strong>Background.</strong> Evidence suggests that the presence of mental illness may be associated with poorer adherence to antiretroviral therapy (ART). There is also a general understanding that patients initiated on ART as inpatients have poorer outcomes than those initiated as outpatients. Negative perceptions regarding future adherence may affect the clinical decision to initiate ART in hospitalised psychiatric patients. Attendance at clinic appointments is an indicator of medication adherence, and is easily measurable in a limited-resource setting. </p><p><strong>Objectives.</strong> The primary objective of this study was to examine the rate of attendance at the first clinic appointment post discharge from a period of psychiatric hospitalisation in HIV-positive psychiatric patients initiated on ART as inpatients. A secondary objective was to determine which factors, if any, were associated with clinic attendance. </p><p><strong>Methods.</strong> This study was a retrospective record review, conducted at the Luthando Neuropsychiatric HIV Clinic in Soweto, which is an integrated mental healthcare and ART clinic. Patients who were initiated on ART as psychiatric inpatients from 1 July 2009 to 31 December 2010, and subsequently discharged for outpatient follow-up at Luthando Clinic were included in the sample. </p><p><strong>Results.</strong> There were 98 patients included in the analysis. The sample was predominantly female. The rate of attendance was 80%. The attendant and non-attendant groups were similar in terms of demographic and clinical data. Significantly fewer non-attendant patients had disclosed their HIV status to their treatment supporter (<em>p</em>=0.01). </p><p><strong>Conclusion.</strong> Non-disclosure of HIV status needs to be further addressed in integrated psychiatric HIV treatment facilities in order to improve attendance. Female predominance in this setting should also be further investigated.</p>
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Siegel, Robert D., Hal E. Crosswell, Terra Dillard, Jennifer Bayne, Tina Redenz, Kyle Duggan, and Angela Belew. "Interdisciplinary care rounds in the community: Changing the paradigm of supportive service involvement in cancer care." Journal of Clinical Oncology 34, no. 7_suppl (March 1, 2016): 83. http://dx.doi.org/10.1200/jco.2016.34.7_suppl.83.
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83 Background: Although cancer centers have focused on optimizing seamless Multidisciplinary Care (MDC) at tumor boards and/or clinics, there has been little published on effective ways to involve supportive services into the management of cancer patients. Historically, supportive services have been initiated when there is an active need rather than in anticipation of that need. As an alternative to pursuing such "crisis management" in our patients, Bon Secours St. Francis Cancer Center (BSSF) initiated Interdisciplinary Care (IDC) Rounds in an effort to anticipate patient needs, enhance quality of life (QoL), and potentially limit avoidable emergency room and hospital admissions. Methods: We initiated IDC Rounds with participants from the following disciplines: medical oncology, navigation, clinic nursing, palliative medicine, financial counseling, psychology, nutrition, clinical research, adolescent and young adult, and oncology rehabilitation/survivorship (ORS). A database was created to track new patients with malignancies within three weeks of presentation and the subsequent recommendations made by the IDC team. Those recommendations are then forwarded to the primary medical oncologist who has the ability to agree to those recommendations in full or in part before they are actuated. Results: BSSF is a non-academic, community-based cancer program and receives over 1,300 referrals annually from a referral population of 1.32 million in 10 counties. Short term metrics demonstrate a 57% and 100% increase in referrals to ORS and palliative care, respectively. Successes and challenges including sustainability, cost and measurable impact will be discussed. Conclusions: We have shown that it is feasible in the community setting to create a process that will allow early integration of supportive services into the full service care of cancer patients. Results demonstrate an increase in short-term metrics such as referrals to supportive services. Our ultimate goal is that formalized IDC results not only in earlier involvement by needed services but enhanced QoL for our patients with fewer emergency room and hospital admissions. Those data will be compiled as the program matures.
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Chu, Peter C. "Technical note: Two types of absolute dynamic ocean topography." Ocean Science 14, no. 5 (September 4, 2018): 947–57. http://dx.doi.org/10.5194/os-14-947-2018.
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Abstract. Two types of marine geoid exist with the first type being the average level of sea surface height (SSH) if the water is at rest (classical definition), and the second type being satellite-determined with the condition that the water is usually not at rest. The differences between the two are exclusion (inclusion) of the gravity anomaly and non-measurable (measurable) in the first (second) type. The associated absolute dynamic ocean topography (referred to as DOT), i.e., SSH minus marine geoid, correspondingly also has two types. Horizontal gradients of the first type of DOT represent the absolute surface geostrophic currents due to water being at rest on the first type of marine geoid. Horizontal gradients of the second type of DOT represent the surface geostrophic currents relative to flow on the second type of marine geoid. Difference between the two is quantitatively identified in this technical note through comparison between the first type of DOT and the mean second type of DOT (MDOT). The first type of DOT is determined by a physical principle that the geostrophic balance takes the minimum energy state. Based on that, a new elliptic equation is derived for the first type of DOT. The continuation of geoid from land to ocean leads to an inhomogeneous Dirichlet boundary condition with the boundary values taking the satellite-observed second type of MDOT. This well-posed elliptic equation is integrated numerically on 1∘ grids for the world oceans with the forcing function computed from the World Ocean Atlas (T, S) fields and the sea-floor topography obtained from the ETOPO5 model of NOAA. Between the first type of DOT and the second type of MDOT, the relative root-mean square (RRMS) difference (versus RMS of the first type of DOT) is 38.6 % and the RMS difference in the horizontal gradients (versus RMS of the horizontal gradient of the first type of DOT) is near 100 %. The standard deviation of horizontal gradients is nearly twice larger for the second type (satellite-determined marine geoid with gravity anomaly) than for the first type (geostrophic balance without gravity anomaly). Such a difference needs further attention from oceanographic and geodetic communities, especially the oceanographic representation of the horizontal gradients of the second type of MDOT (not the absolute surface geostrophic currents).
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Staehler, Maya, Clark Benson, Jordan Madden, Laura Block, and Andrea Gilmore-Bykovskyi. "Initial Derivation of Positive Dementia-Related Observational Measures: A Descriptive Ethnography." Innovation in Aging 4, Supplement_1 (December 1, 2020): 164. http://dx.doi.org/10.1093/geroni/igaa057.531.
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Abstract Person-centered caregiving approaches emphasize efforts to protect and maintain the personhood of people living with dementia (PLWD). The influence on person-centered caregiving approaches on PLWD have predominantly focused on deficit-oriented outcomes, such as absence or reduction of behavioral symptoms. While important to quality of life, the absence of measurable “positive” responses to person-centered caregiving approaches limit opportunities to specify sensitive and meaningful outcome measures that more holistically represent PLWD’s care experiences as more than the absence of a negative outcome. To address these gaps, we conducted a secondary analysis of video-observations of PLWD (N=9) surrounding mealtime cares using a descriptive ethnographic approach. Our objectives were to descriptively summarize specific responsive behaviors demonstrated by PLWD surrounding person-centered caregiving interactions, specifying observable features of these responses and consider their utility in future video-observational research. Findings indicate PLWD contribute both verbal and non-verbal communication surrounding person-centered approaches which can be characterized as conversational (starting conversation, answering or asking questions), expressing preferences (indicating needs and preferences, agreeing or disagreeing, complying with or refusing caregiver requests, permission granting), emotional responses (mirroring caregivers’ emotions, demonstrating emotion e.g. smiling), and reflexive (mirroring of caregiver’s actions), with overlap between categories. Findings suggest that PLWD not only contribute and respond in meaningful ways to person-centered interactions, but also initiate a significant number of these interactions. This study contributes to a growing body of research and advocacy that examines the personhood and abilities of PLWD and establishes the utility of observational data in studying PLWD contributions.
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Essex, B., S. H. A. Koop, and C. J. Van Leeuwen. "Proposal for a National Blueprint Framework to Monitor Progress on Water-Related Sustainable Development Goals in Europe." Environmental Management 65, no. 1 (December 3, 2019): 1–18. http://dx.doi.org/10.1007/s00267-019-01231-1.
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AbstractThe 17 Sustainable Development Goals (SDGs) underpinned by 169 targets presents national governments with huge challenges for implementation. We developed a proposal for a National Blueprint Framework (NBF) with 24 water-related indicators, centered on SDG 6 (clean water and sanitation for all), each with a specific target. We applied the NBF to 28 EU Member States (EU-28) and conclude that: The current SDG 6 indicators are useful for monitoring progress toward water-related targets but their usefulness can be improved by focusing more on their practical implementation. The extension of SDG 6 with complementary indicators (e.g. for the circular economy of water) and quantitative policy targets is urgently needed. This will benefit the communication process and progress at the science-policy interface. SDG indicators can be improved in a SMART (specific, measurable, achievable, relevant, and time-bound) manner and by setting clear policy targets for each indicator, allowing for measuring distance-to-targets. This allows country-to-country comparison and learning, and accelerates the SDG implementation process. We propose 24 water-related indicators centered on SDG 6, with complementary indicators including quantitative policy targets. The approach is doable, easily scalable, and flexibly deployable by collecting information for the EU-28. Main gaps in the EU-28 are observed for water quality, wastewater treatment, nutrient, and energy recovery, as well as climate adaptation to extreme weather events (heat, droughts, and floods). The framework was less successful for non-OECD countries due to lack of data and EU-centric targets for each indicator. This needs further research.
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Choi, Yoon-A., Se-Jin Park, Jong-Arm Jun, Cheol-Sig Pyo, Kang-Hee Cho, Han-Sung Lee, and Jae-Hak Yu. "Deep Learning-Based Stroke Disease Prediction System Using Real-Time Bio Signals." Sensors 21, no. 13 (June 22, 2021): 4269. http://dx.doi.org/10.3390/s21134269.
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The emergence of an aging society is inevitable due to the continued increases in life expectancy and decreases in birth rate. These social changes require new smart healthcare services for use in daily life, and COVID-19 has also led to a contactless trend necessitating more non-face-to-face health services. Due to the improvements that have been achieved in healthcare technologies, an increasing number of studies have attempted to predict and analyze certain diseases in advance. Research on stroke diseases is actively underway, particularly with the aging population. Stroke, which is fatal to the elderly, is a disease that requires continuous medical observation and monitoring, as its recurrence rate and mortality rate are very high. Most studies examining stroke disease to date have used MRI or CT images for simple classification. This clinical approach (imaging) is expensive and time-consuming while requiring bulky equipment. Recently, there has been increasing interest in using non-invasive measurable EEGs to compensate for these shortcomings. However, the prediction algorithms and processing procedures are both time-consuming because the raw data needs to be separated before the specific attributes can be obtained. Therefore, in this paper, we propose a new methodology that allows for the immediate application of deep learning models on raw EEG data without using the frequency properties of EEG. This proposed deep learning-based stroke disease prediction model was developed and trained with data collected from real-time EEG sensors. We implemented and compared different deep-learning models (LSTM, Bidirectional LSTM, CNN-LSTM, and CNN-Bidirectional LSTM) that are specialized in time series data classification and prediction. The experimental results confirmed that the raw EEG data, when wielded by the CNN-bidirectional LSTM model, can predict stroke with 94.0% accuracy with low FPR (6.0%) and FNR (5.7%), thus showing high confidence in our system. These experimental results demonstrate the feasibility of non-invasive methods that can easily measure brain waves alone to predict and monitor stroke diseases in real time during daily life. These findings are expected to lead to significant improvements for early stroke detection with reduced cost and discomfort compared to other measuring techniques.
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Srinivas, Gunda. "Healthcare Innovation and Design Thinking." Karnataka Pediatric Journal 36 (September 6, 2021): 87–93. http://dx.doi.org/10.25259/kpj_14_2021.
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The objective of this article is to bring awareness to the changing landscape of the healthcare ecosystem and the clinician’s role with respect to medical devices, medical systems, technology, and processes involved in the system. Clinicians interact with them every day and have a huge implication for them directly, and to their patients indirectly. Clinicians are actively involved in clinical research which involves the knowledge and practice of the disease, diagnosis and management, etc. Recently, the role of non-clinical aspects such as medical devices, processes and systems of the healthcare ecosystem is gaining popularity. Hence, there is potential to explore this aspect of the healthcare delivery system to redesign and innovate for improving clinical outcomes. To achieve this, the clinicians need to understand these systems from a perspective that will help them to identify the problems and develop innovative solutions. Just like the clinical research is systematic and methodical, the improvement of the medical systems is also methodical to a large extent. This includes concepts and techniques that are quite fresh and new to a clinician who probably has never been exposed to these in their medical careers. These general principles of Innovation and Design thinking applied to other domains have yielded fantastic results and for the same to be applied in the medical domain, the role of the practicing clinician is central. As clinicians, we have always practiced innovation at some point of time in our career when we would have faced a resource crunch and were compelled to save the children and hence have tried to innovate on the devices, processes, etc., in our own way and has worked many a times. To generate many such solutions at large scale, the whole process needs to be methodical and systematic so that the solutions developed are safe and consistent at all times. Such a solution can be scaled up and made to reach across such setups where it is needed and there can be a measurable improvement in efficiency, quality, effectiveness, or economics of patient care delivery on a large scale.
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Rauthan, Amit, Poonam Patil, S. P. Somashekhar, and Shabber Zaveri. "A regimen of weekly nab-paclitaxel with weekly carboplatin in recurrent ovarian cancer: A retrospective analysis." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): e15516-e15516. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e15516.
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e15516 Background: The standard of care for patients with recurrent platinum resistant ovarian cancer is treatment with non cross-resistant drugs. Carboplatin retreatment is usually not an option in the platinum resistant population. Weekly paclitaxel has been tried in recurrent patients. But paclitaxel can cause hypersensitivity reactions due to its Cremophor based solvent. nab-paclitaxel being a nano-particle albumin bound paclitaxel is devoid of this toxictity. Also, it is thought that nab-paclitaxel may have a higher intratumoral uptake leading to enhanced anti-tumor action. We looked at a regimen using weekly carboplatin with weekly nab-paclitaxel in platinum resistantrelapsed carcinoma ovary who had failed multiple lines of treatment. Methods: We treated 10 patients with recurrent platinum resistant ovarian cancer with measurable disease with nab-paclitaxel 100mg/m2 on days 1,8,15 with carboplatin at AUC 1.5 on days 1,8,15 intravenously, repeated every 28 days for 4 cycles. All patients had received 3 or more lines of chemotherapy for recurrent disease. We looked for response rate, progression free survival and toxicities. Results: Three patients had complete response, 5 patients had partial response and 2 patients had disease progression. Median PFS was 6 months. There were no instances of paclitaxel induced hypersensitivity reactions. Two patients developed grade 3 neutropenia. One patient developed grade 3 thrombocytopenia. Three patients required blood transfusions. One patient developed grade 3 neuropathy. Conclusions: Weekly combination of nab-paclitaxel with weekly carboplatin is a safe and potentially active treatment in recurrent platinum resistant ovarian cancers who had failed multiple lines of treatment. Considering the efficacy and favorable toxicity profile, this weekly combination needs to be tested in a larger number of patients.
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Apple, Fred S., Alan H. B. Wu, Yader Sandoval, Anne Sexter, Sara A. Love, Gary Myers, Karen Schulz, Show-Hong Duh, and Robert H. Christenson. "Sex-Specific 99th Percentile Upper Reference Limits for High Sensitivity Cardiac Troponin Assays Derived Using a Universal Sample Bank." Clinical Chemistry 66, no. 3 (January 27, 2020): 434–44. http://dx.doi.org/10.1093/clinchem/hvz029.
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Abstract Background How to select healthy reference subjects in deriving 99th percentiles for cardiac troponin assays still needs to be clarified. To assist with global implementation of high sensitivity (hs)-cardiac troponin (cTn) I and hs-cTnT assays in clinical practice, we determined overall and sex-specific 99th percentiles in 9 hs-cTnI and 3 hs-cTnT assays using a universal sample bank (USB). Methods The Universal Sample Bank (USB) comprised healthy subjects, 426 men and 417 women, screened using a health questionnaire. Hemoglobin A1c (>URL 6.5%), NT-proBNP (>URL 125 ng/L) and eGFR (<60 mL/min), were used as surrogate biomarker exclusion criteria along with statin use. 99th percentiles were determined by nonparametric, Harrell--Davis bootstrap, and robust methods. Results Subjects were ages 19 to 91 years, Caucasian 58%, African American 27%, Pacific Islander/Asian 11%, other 4%, Hispanic 8%, and non-Hispanic 92%. The overall and sex-specific 99th percentiles for all assays, before and after exclusions (n = 694), were influenced by the statistical method used, with substantial differences noted between and within both hs-cTnI and hs-cTnT assays. Men had higher 99th percentiles (ng/L) than women. The Roche cTnT and Beckman and Abbott cTnI assays (after exclusions) did not measure cTn values at ≥ the limit of detection in ≥50% women. Conclusions Our findings have important clinical implications in that sex-specific 99th percentiles varied according to the statistical method and hs-cTn assay used, not all assays provided a high enough percentage of measurable concentrations in women to qualify as a hs-assay, and the surrogate exclusion criteria used to define normality tended to lower the 99th percentiles.
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Lasminingrat, Lula, and Efriza Efriza. "THE DEVELOPMENT OF NATIONAL FOOD ESTATE: THE INDONESIAN FOOD CRISIS ANTICIPATION STRATEGY." Jurnal Pertahanan & Bela Negara 10, no. 3 (December 23, 2020): 229. http://dx.doi.org/10.33172/jpbh.v10i3.1110.
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<p><em>Indonesia responds to the urgency of the threat of food crisis by </em><em>developing</em><em> national food estate. According to reports released by FAO and United Nations, the Covid-19 pandemic has the potential to threaten more than 50 million people towards extreme poverty. This has an impact on the global food crisis that threatens other countries if they do not take the right steps immediately. Food crisis is one of the non-traditional threats because it has significant impact on lives of many people in a country. Non-traditional threats are defined as security threats that hit a country non-militarily, it can be in the form of issues of climate change, economy, limited resources, disease outbreaks, or food security. Food security can be achieved when access to food can be easily achieved by all elements of society and meets the domestic needs. However, when access to food cannot be easily accessed by public, it creates a potential for a food crisis. This is because food is the primary need of every individual which must be fulfilled at any time so it is a national security issue. Through these problems, the availability of national food security must be guaranteed by the government. Along with high population growth and a pandemic outbreak, national food security and stability is on the verge of limitations. This article aims to explain the development of food estate as Indonesia’s strategy in facing the threat of food crisis in the next few years. This research used qualitative analysis method to understand the urgency of the development of food estate as a way for Indonesia to face the threat of food crisis by using the theory of threats, food security, and food estate. In this case, Jokowi responded to the threat of the food crisis by building national food estate in Central Kalimantan. The development of national food estate is considered to be able to meet Indonesia’s food reserves in the next few years, especially after the pandemic period. The results of the research in this article show that the government sees the potential for the food crisis as a national threat, so it needs measurable steps that can overcome these problems and pay attention to the sustainability aspect in its implementation. Therefore, building a food estate is the right step to answer this challenge.</em></p><p><strong><em>Keywords: </em></strong><em>n</em><em>on-</em><em>t</em><em>raditional </em><em>t</em><em>hreat, </em><em>f</em><em>ood </em><em>c</em><em>rises, </em><em>f</em><em>ood </em><em>s</em><em>ecurity, </em><em>f</em><em>ood </em><em>e</em><em>state, national security</em></p>
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Wang, Jiangning, Congtian Lin, Yan Han, and Liqiang Ji. "Discussion of the Method for Constructing Animal Traits." Biodiversity Information Science and Standards 2 (April 25, 2018): e26168. http://dx.doi.org/10.3897/biss.2.26168.
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Trait data in biology can be extracted from text and structured for reuse within and across taxa. For example, body length is one trait applicable to many species and "body length is about 170 cm" is one trait data point for the human species. Trait data can be used in more detailed analyses to describe species evolution and development processes, so it has begun to be valued by more than taxonomists. The EOL (Encyclopedia of Life) TraitBank provides an example of a trait database. Current trait databases are in their infancy. Most are based on morphological data such as shape, color, structural and sexual characteristics. In fact, some data such as behavioral and biological characteristics may be similarly included in trait databases. To build a trait database we constructed a list of controlled vocabulary to record the states of various terms. These terms may exhibit common characteristics: They can be grouped as conceptual (subject) and descriptive (delimiter) terms. For example, in “the shoulder height is 65–70 cm”, "shoulder height" is the conceptual term and "65–70 cm" is the descriptive term. Conceptual terms may be part of an interdependent hierarchical structure. Examples in morphology, physiology and conservation or protection status, demonstrate how parts or systems may be broken into smaller measurable (quantifiable) or enumerable pieces. Descriptive terms will modify or delimit parameters of conceptual terms. These may be numerical with distinguishing units, counts, or other adjectives or enumerable with special nouns. They can be grouped as conceptual (subject) and descriptive (delimiter) terms. For example, in “the shoulder height is 65–70 cm”, "shoulder height" is the conceptual term and "65–70 cm" is the descriptive term. Conceptual terms may be part of an interdependent hierarchical structure. Examples in morphology, physiology and conservation or protection status, demonstrate how parts or systems may be broken into smaller measurable (quantifiable) or enumerable pieces. Descriptive terms will modify or delimit parameters of conceptual terms. These may be numerical with distinguishing units, counts, or other adjectives or enumerable with special nouns. Although controlled vocabularies about animals are complex, they can be normalized using RDF (Resource Description Framework) and OWL (web ontology language) standards. Next, we extract traits from two main types of existing descriptions. tabular data, which is more easily digested by machine, and descriptive text, which is complex. tabular data, which is more easily digested by machine, and descriptive text, which is complex. Pure text often needs to be extracted manually or by NLP (computerized natural language processing). Sometimes machine learning methods can be used. Moreover, different human languages may demand different extraction methods. Because the number of recordable traits exceeds current collection records, the database structure should be optimized for retrieval speed. For this reason, key-value databases are more suitable for storage of traits data than relational databases. EOL used the database Virtuoso for Traitbank, which is a non-relational database. Using existing mature tools and standards of ontology, we can construct a preliminary work-flow for animal trait data, but some tools and specifications for data analysis and use need to await additional data accumulation.
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Ugurel, S., K. Neuber, C. Pfoehler, C. Mauch, J. Ulrich, and D. Schadendorf. "Pegylated liposomal doxorubicin plus paclitaxel as an individualized chemosensitivity-directed treatment in advanced metastatic melanoma." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 8551. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.8551.
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8551 Background: Melanoma is a cutaneous neoplasm known for its high agressiveness and its poor prognosis once metastasized. Dacarbacine chemotherapy is actually considered standard first-line treatment of metastatic melanoma, with reported response rates of 6–7%. Due to this unsatisfactory situation, a number of non-standard anti-cancer drugs have been tested for improved efficacy. The present study was aimed to test doxorubicin plus paclitaxel in metastatic melanoma patients based on in-vitro chemosensitivity of this drug combination in fresh tumor samples. Methods: The primary study endpoint was objective response, secondary endpoints were safety and overall survival. Patients with histologically confirmed metastatic melanoma (AJCC stage IV), measurable tumor parameters, and an in-vitro chemosensitivity to doxorubicin plus paclitaxel which is superior to other test drugs determined by an ATP-based luminescence viability assay, were eligible. Patients received paclitaxel 175 mg/m2 i.v. followed by pegylated liposomal doxorubicin 30 mg/m2 i.v. at d1 every 28 days. Tumor assessment was performed every 8 weeks and evaluated according to RECIST. Treatment was continued at a tumor response of stable disease (SD) or better, and stopped in case of disease progression (PD) or intolerable side effects. Results: Out of 14 patients enrolled into this study, 12 received study treatment as first-line, and two as second-line therapy. Objective response was 14.3% (1 CR, 1 PR); progression arrest was 28.6% (1 CR, 1 PR, 2 SD). Median overall survival was 9.7 months. Common slight to moderate side effects were myelosuppression and neurotoxicity. Severe toxicities (CTC grade 3/4) were experienced by three patients (21.4%), with two of them presenting severe myelosuppression, and one experiencing myocardial infarction. Conclusions: Pegylated liposomal doxorubicin combined with paclitaxel shows significant efficacy in advanced metastatic melanoma if applied in an individualized, sensitivity- directed regimen. The observed side effects were comparable to other combination chemotherapies. This treatment regimen needs further evaluation in larger clinical trials containing standard therapy control groups. No significant financial relationships to disclose.
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Amirabedini, Atousa. "Two development theories: Ibn-i-Khaldoun and Wallerstein." Campus-Wide Information Systems 31, no. 1 (December 20, 2013): 63–74. http://dx.doi.org/10.1108/cwis-08-2013-0035.
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Purpose – Each day, many different people in different societies are striving within their daily work to advance society. Every society needs to create ideas for further development and in order to become recognised as developed. The purpose of this paper is to show how different cultures at different times created similar ideas and theories to develop their society. Design/methodology/approach – A comparison between the development theories of Ibn-i-Khaldun and Wallerstein's famous “world system theory” is undertaken to show that similar ideas of development were in existence even centuries before. Technically, seminar papers were posted and reviewed on an e-learning platform in order to reach such peer-reviewed assessment in a “Global Studies” curriculum. Findings – The paper shows that the similarity between all developed countries is a strong state and extensive economic activity in different areas among cooperative people. All of these three characteristics are measurable and visible in today's western societies, and also centuries before in other countries (the Golden Age of the Muslim World). Research limitations/implications – Limits to comparing the two development theories of Ibn-i-Khaldun with Wallerstein's world system theory arise because of the large gap in time and the big cultural differences between the authors of the two theories. There is, on one side, Ibn-i-Khaldun in the thirteenth century whose religion (Islam) played an important role in his development theory and on the other side there is a western author, Immanuel Wallerstein in the twentieth century. In Wallerstein's development theory, religion has almost no role. Another point is that Wallerstein's theory provides a guideline to almost all countries for reaching development but Ibn-i-Khaldun's target countries are the Muslim countries which were experiencing decline at his time. Originality/value – Unlike traditional approaches, the present analysis includes early scientific theories from non-European authors. Thus, one of the main objectives of “Global Studies” is fulfilled; namely a trans-disciplinary, globalised perspective.
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Gillison, T. L., L. J. Appleman, D. M. Friedland, T. L. Evans, P. N. Lara, W. E. Gooding, D. E. Lenzner, H. M. Strausser, J. R. Gingrich, and G. S. Chatta. "Docetaxel and imatinib every 21 days for castration resistant prostate cancer: A phase II trial." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e16086-e16086. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e16086.
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e16086 Background: Docetaxel (D) IV every 21 days, is the only cytotoxic agent that prolongs survival in men with castrate resistant prostate cancer (CRPC). Imatinib (I), a tyrosine kinase inhibitor, modulates PDGFR-ß in tumor vasculature. Based on phase I data from our institution, we hypothesized that D plus I would prolong time to progression (TTP) in patients (pts) with CRPC. Methods: Subjects with CRPC received D 60 mg/m2 IV every 21 days plus I 400 mg PO daily. After 10 pts, the study treatment was modified due to toxicity so that pts received I 400 mg on 10 of 21 days/cycle. The primary endpoint was TTP. Secondary endpoints were rate of PSA response and overall survival (OS). The sample size of 43 pts was designed to provide 90% power to detect an increase in TTP from 5 to 8 months. Results: 43 pts enrolled from 8/05 to 9/08. Age at enrollment ranged from 54–86 years (median 69 years). 14 pts received <1 cycle of D plus I and were unevaluable: 10 had significant toxicity, 4 due to non-treatment related reasons. Primary toxicities were hematologic: 21% G4 neutropenia, 5% G4 anemia, and no G4 thrombocytopenia. Fatigue, nausea, diarrhea, and electrolyte abnormalities were common, but <2 cases each of G3-G4 toxicity occurred. 1 case of G5 non-neutropenic sepsis occurred. 29 pts received >2 cycles of chemotherapy (mean 4.6). 12 pts had PR (41.4%), 9 had SD (31.0%), and 8 had no response (27.6%) by PSA. No objective responses were seen by CT imaging among 10 pts with measurable disease. 3 pts remain on trial. For evaluable pts, overall median TTP was 6.4 months (95% CL: 4.8, 8.4 months) compared with TTP of 5 months seen in previous trials. 23 (79%) pts had PSA progression, 3 pts died before progression, and 3 pts remain on trial. For all evaluable pts who had PR or SD by PSA (N = 21), median TTP was 7.1 months (95% CL: 5.5, 9.1 months). Median OS was 23.1 months (95% CL: 11.61 months, NR), compared with 18.9 months for GC Conclusions: Docetaxel on day 1 plus imatinib 10 days of each 21-day cycle resulted in meaningful improvement in TTP in the subset of pts who showed a response. Toxicity precludes its use in the general population, although its role in select pts with good performance status needs to be explored. [Table: see text]
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Rajkai, Kálmán, K. R. Végh, and T. Nacsa. "Electrical Capacitance as the Indicator of Root Size and Activity." Agrokémia és Talajtan 51, no. 1-2 (March 1, 2002): 89–98. http://dx.doi.org/10.1556/agrokem.51.2002.1-2.11.
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A new method is introduced to agricultural practice for measuring the living active root of the plants. The measured root capacitance is interpreted in electro-chemical principles. In addition to the electrochemical interpretation of the measurements we aimed to find a non-wounding electrode instead of the needle plant electrode. Another reason for dealing with the tweezer plant electrode was to decrease the relatively high standard deviation of the root capacitance readings due to the relatively high uncertainty of hitting the xylem with the needle plant electrode. To improve and standardize the contact between the tweezer plant electrode and the stem a high electrical conductivity gel (UNIGEL) was applied on the stem before clipping the tweezers. Experiments for the root capacitance measurements were made in temperature and light controlled climate chambers (Conviron, Canada) in 2 litre plastic pots filled with 4:1 soil:sand mixture and water culture. Comparison of the root capacitances of five-week old sunflower plants measured with the needle and the tweezer plant electrodes proved identical in water culture and capillary water saturated soil. However, the applicability of the tweezer plant electrode needs further study for other plants and environmental conditions. The effect of measurement frequency on root capacitance and resistance with the HP4284A impedance bridge was also studied to see the effectiveness of polarization (Figure 1). From Figure 1 it can be seen that root capacitance decreased at frequencies above 1 kHz, while it increased up to the dielectric constant of water at lower frequencies. An interpretation of measurable root capacitance in the soil-plant system is given using separate measured plant tissue and soil capacitances. We established that root capacitance in the soil-plant system approximates the capacitance of the root tissue. Good correlation was found between root capacitance and the calculated root surface area (RA) for sunflower plants (Figure 2). The GW LCR-814 was found suitable for making root capacitance measurements. Finally, further experimental work is needed to collect information for the more general and extended applicability of the method before it becomes a routine tool in ecological and agricultural practice.
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Chen, L. "Phase II trial of S-1 combined with oxaliplatin (SOX) as neoadjuvant chemotherapy for locally advanced gastric cancer." Journal of Clinical Oncology 29, no. 4_suppl (February 1, 2011): 122. http://dx.doi.org/10.1200/jco.2011.29.4_suppl.122.
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122 Background: Previous phase II trial with combination therapy of S-1 plus oxaliplatin (SOX) demonstrated high response rate and well tolerability in patients with untreated advanced gastric cancer. The aim of this phase II trial was to evaluate the efficacy and safety of SOX as neoadjuvant chemotherapy for locally advanced gastric cancer (AGC). Methods: Eligibility criteria included a histologically proven AGC with stage IIIb, IIIc (AJCC 7th edition), at least 1 measurable lesion, no prior chemotherapy, ECOG 0∼2, adequate hepatic, renal, and bone marrow function. Enrolled patients were staged by EUS and CT. The neoadjuvant chemotherapy consisted of 3-4 cycles of oxaliplatin (130 mg/m2) on day 1 and S-1 (80 mg/m2/day) for 14 days with 7 days rest. After chemotherapy, the patients underwent surgery. Results: From Dec 2009 to Sep 2010, 35 patients (IIIb; 19pts, IIIc; 16pts) were enrolled. The median age of the patients was 54.6 years (range; 20-72 y). All patients were available for evaluating the clinical responese and adverse events. The overall response rate was 68.5% (1CR, 23 PR, 9 SD, 2 PD). 32 patients underwent surgical resection. Of them, 27 patients underwent standard D2 surgery and 5 patients had palliative surgery. 25 patients had R0 resection. Postoperative pathological examination showed that most of the surgical patients were in T4a stage. According to Lauren classification, 71.9% patiens (23/32pts) were diffuse type, SOX showed higher respons rate (1CR, 20 PR, 2 SD, RR: 91.3%) among these patients. Major grade 3/4 hematological toxicities were anemia (5.7%), neutropenia (5.7%) and liver dysfunction (8.6%) and non-hematological toxicities were anorexia (5.7%) and vomiting (11.4%). But most of the adverse events were managable. Conclusions: Neoadjuvant chemotherapy with S-1 plus oxaliplatin (SOX) showed high response rate and and R0 resection rate for locally advanced GC, especially for diffuse type patients. All the patients did not have severe toxicity during the process of chemotherapy. This is the preliminary results, and the survival benefit in locally advanced GC patients that respond to SOX neoadjuvant chemotherapy needs to be addressed by a randomized-controlled trial. No significant financial relationships to disclose.
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Knoke, Thomas, Mengistie Kindu, Thomas Schneider, and Terje Gobakken. "Inventory of Forest Attributes to Support the Integration of Non-provisioning Ecosystem Services and Biodiversity into Forest Planning—from Collecting Data to Providing Information." Current Forestry Reports 7, no. 1 (February 15, 2021): 38–58. http://dx.doi.org/10.1007/s40725-021-00138-7.
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Abstract Purpose of Review Our review provides an overview of forest attributes measurable by forest inventory that may support the integration of non-provisioning ecosystem services (ES) and biodiversity into forest planning. The review identifies appropriate forest attributes to quantify the opportunity for recreation, biodiversity promotion and carbon storage, and describes new criteria that future forest inventories may include. As a source of information, we analyse recent papers on forest inventory and ES to show if and how they address these criteria. We further discuss how mapping ES could benefit from such new criteria and conclude with three case studies illustrating the importance of selected criteria delivered by forest inventory. Recent Findings Recent studies on forest inventory focus mainly on carbon storage and biodiversity promotion, while very few studies address the opportunity of recreation. Field sampling still dominates the data collection, despite the fact that airborne laser scanning (ALS) has much improved the precision of large-scale estimates of the level of forest ES provision. However, recent inventory studies have hardly addressed criteria such as visible distance in stands, presence of open water bodies and soil damages (important for the opportunity of recreation) and naturalness (here understood as the similarity of the forest to its natural state) and habitat trees and natural clearings (important for biodiversity promotion). The problem of quantifying carbon stock changes with appropriate precision has not been addressed. In addition, the reviewed studies have hardly explored the potential of inventory information to support mapping of the demand for ES. Summary We identify challenges with estimating a number of criteria associated with rare events, relevant for both the opportunity of recreation and biodiversity promotion. These include deadwood, rare species and habitat trees. Such rare events require innovative inventory technology, such as point-transect sampling or ALS. The ALS technology needs relatively open canopies, to achieve reliable estimates for deadwood or understorey vegetation. For the opportunity of recreation, the diversity among forest stands (possibly quantified by geoinformatics) and information on the presence of open water bodies (provided by RADAR, ALS data or use of existing maps) may be important. Naturalness is a crucial criterion for native biodiversity promotion but hard to quantify and assess until now. Tree species identification would be crucial for this criterion, which is still a challenge for remote sensing techniques. Estimating carbon storage may build on biomass estimates from terrestrial samples or on remotely sensed data, but major problems exist with the precision of estimates for carbon stock changes. Recent approaches for mapping the supply side of forest ES are promising, while providing so far uncommon structural information by revised inventory concepts could be helpful also for mapping the demand for ES. We conclude that future studies must find holistic inventory management systems to couple various inventory technologies in support of the integration of non-provisioning ES and biodiversity into forest planning.
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Böhm, Martina, Manuela Krause, Charis Von Auer, Wolfgang Miesbach, and Inge Scharrer. "The Frequency and the Significance of ADAMTS-13 Neutralising Inhibitors in 62 Patients with Non-Familial Thrombotic Thrombocytopenic Purpura." Blood 104, no. 11 (November 16, 2004): 3945. http://dx.doi.org/10.1182/blood.v104.11.3945.3945.
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Abstract Neutralising inhibitors against ADAMTS-13 are detected in 51–67% of patients with Thrombotic Thrombocytopenic Purpura (TTP). These ADAMTS-13 inhibitors have not been very well characterised and the diagnostic or the prognostic value of these inhibitors is not established. In the present study, we measured ADAMTS-13 activity and the corresponding inhibitor titer in 96 samples from 62 patients with TTP at various stages of their disease. All patients presented with non-familial TTP. For patients with severe ADAMTS-13 activity without detectable inhibitor heritable ADAMTS-13 deficiency was excluded by either normalisation of ADAMTS-13 activity in remission or by detecting normal ADAMTS-13 activity in first degree family members. ADAMTS-13 activity was quantified by measuring the residual ristocetin cofactor activity of the substrate. The inhibitor against ADAMTS-13 was detected by mixing patient plasma, either neat or diluted, with normal plasma. The inhibitor concentration neutralising 50% of ADAMTS-13 activity in a 1:1 dilution of patient plasma with normal plasma was defined as 1 U/ml. Inhibitors were considered non-detectable (<0.4 U/ml), if residual ADAMTS-13 activity in the mixture was higher than 75%. Samples with ADAMTS-13 activity >6.25% were heat-inactivated (30 min at 56°C) before testing for inhibitory activity. We found severe ADAMTS-13 deficiency in 89% (24/27) of the samples from patients with acute untreated TTP. 87% (21/24) of these samples were positive for inhibitory activity. The inhibitor titer ranged from 0.4 to 62 U/ml with a median of 1 U/ml. One patient with acute TTP demonstrated ADAMTS-13 activity of 34% despite an inhibitor titer of 0.6 U/ml. The sensitivity of a positive inhibitor test for the diagnosis of TTP was thus 82%. The inhibitor titer before initiation of therapy could not be correlated with the platelet count, the CRP-level or the response to PE-therapy, if patients with an index episode and patients with a relapse were analysed separately. Severe ADAMTS-13 activity was detected in 15/31 samples collected from patients during plasma exchange therapy. 93% (14/15) of these samples were positive for an inhibitor with a titer ranging between 0.6 and 47 U/ml (median: 3 U/ml). 12 of 37 patients tested in remission presented with severe ADAMTS-13 deficiency, 6 of them were positive for inhibitory activity (range: 1–52 U/ml; median: 5 U/ml). The inhibitor titer for patients, which were analysed during acute untreated TTP as well as in remission (n=5), was notable not related to the stage of disease. Five patients with positive inhibitory activity at admission demonstrated mild ADAMTS-13 deficiency in remission without detectable inhibitor. In contrast, we detected inhibitory activity of 0,6–0,8 U/ml in 3 samples from two patients with measurable ADAMTS-13 activity. These low titer inhibitors were only detectable, if samples were heat inactivated before performing the inhibitor assay. Our data demonstrate, that inhibitors against ADAMTS-13 are very heterogeneous. It is highly suspected, that some of these inhibitors can either completely or partly neutralise ADAMTS-13 function in vivo without being detectable in vitro. Inhibitors against ADAMTS-13 might, on the other side, not always completely inhibit ADAMTS-13 function, since they can occur in patients with high residual ADAMTS-13 activity. Inhibitor titers show a wide variation and the clinical significance of the inhibitor titer before, during and after therapy needs to be further investigated.
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Jentzsch, Madlen, Sebastian Schwind, Enrica Bach, Sebastian Stasik, Christian Thiede, and Uwe Platzbecker. "Clinical Challenges and Consequences of Measurable Residual Disease in Non-APL Acute Myeloid Leukemia." Cancers 11, no. 11 (October 23, 2019): 1625. http://dx.doi.org/10.3390/cancers11111625.
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The ability to detect residual levels of leukemic blasts (measurable residual disease, MRD) has already been integrated in the daily routine for treatment of patients with chronic myeloid and acute lymphoblastic leukemia. In acute myeloid leukemia (AML), a variety of mostly retrospective studies have shown that individuals in AML remission who tested positive for MRD at specific time-points or had increasing MRD levels are at significantly higher risk of relapse and death compared to MRD-negative patients. However, these studies differ with respect to the “MRD-target”, time-point of MRD determination, material analyzed, and method applied. How this probably very valuable MRD information in individual patients may be adapted in the daily clinical routine, e.g., to separate patients who need more aggressive therapies from those who may be spared additional—potentially toxic—therapies is still a work-in-progress. With the exception of MRD assessment in acute promyelocytic leukemia (APL), the lack of randomized, prospective trials renders MRD-based decisions and clinical implications in AML a difficult task. As of today, we still do not have proof that early intervention in MRD-positive AML patients would improve outcomes, although this is very likely. In this article, we review the current knowledge on non-APL AML MRD assessment and possible clinical consequences.
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Slostad, Jessica, Ashiq Masood, April T. Swoboda, and Mia Alyce Levy. "Towards the clinical validity of tumor organoid drug screens: Establishing a framework for organoid disease models." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): e15037-e15037. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e15037.
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e15037 Background: Despite advances in biomarker-directed cancer therapies to predict tumor response to treatment, precision oncology remains an imprecise science. Tumor organoid drug screens present an opportunity to test multiple potentially effective therapies simultaneously before exposing a patient to treatment toxicities. Preliminary studies have established the analytic validity; however, the clinical validity of the tumor organoid response to a drug to predict the tumor response in patients is unclear. Methods: In order to establish the clinical validity of an organoid drug screen, a clinical disease model should have the following features to enable comparison of the tumor’s clinical response to treatment and the organoid’s response to the same treatment. First, a fresh tissue biopsy (non-bone) needs to be obtained for organoid development prior to the start of systemic treatment. Priority should be given to tumors known to successfully grow organoids. Disease models where the standard of care systemic treatment is a single cytotoxic or targeted agent would best assess correlation between the drug screen and patient response, such as metastatic breast, cervical, or prostate cancer. This would often lead to enrolling patients on later line systemic therapies. Studies should avoid drugs whose mechanism of action leverages the patient metabolism or tumor microenvironment (e.g. immunotherapy, aromatase inhibitors, VEGF inhibitors). Patient should have measurable disease that can be measured clinically, radiographically, or pathologically and using standardized response evaluation criteria (e.g. RECIST). Next generation sequencing would assess genomic concordance between the tumor in the patient and organoid. These studies would determine the feasibility and timeliness of prospectively developing tumor organoids that is sufficient to perform a drug screen. Results: We propose two research models to evaluate the clinical validity of tumor organoid drug screens: a metastatic solid tumor and neoadjuvant solid tumor disease model. Metastatic disease models provide an opportunity to assess response across multiple cancer types at the time of progression and initiation of next line of therapy. The efficacy of chemotherapy can be determined using objective data from radiologic response (RECIST). In neoadjuvant models, pathologic (pCR) and radiologic response can provide objective data for organoid response. These study design features will lay the framework for determining the clinical utility of organoid drug screens. Conclusions: We call for clinical studies assessing the clinical validity of tumor organoid drug screens and determining their concordance with patient response to systemic therapy. Advancements in clinically validated tumor organoids have the potential to fundamentally shift clinical paradigms and improve patient outcomes in cancer treatment.
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Leong, Tze Shin, Sen Mui Tan, Lee Ping Chew, Tee Chuan Ong, Siew Lian Chong, Kar Ying Yong, Siong Leng Hon, et al. "Treatment Outcome and a Practical 10-Point Prognostic Index in Adult Patients with Non-M3 Acute Myeloid Leukemia: A Retrospective, Multicenter Study in Malaysia." Blood 134, Supplement_1 (November 13, 2019): 2606. http://dx.doi.org/10.1182/blood-2019-126656.
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Background: Literature on Acute Myeloid Leukemia (AML) survival and prognostic factors were often derived from strict trial studies from developed country. A simple yet practical prognosis index has not been developed and tested in resource limited setting such as Malaysia. We described the treatment outcome and designed a 10 point prognostic index to predict survival of adult AML (non-M3) in real clinical practice in Malaysia. Methods: Data were retrospectively collected and analyzed from all adults with AML diagnosed and treated from 2007 to 2017 in three main hematology centers in Malaysia, Ampang Hospital, Sarawak General Hospital and Miri General Hospital. Treatment pattern and survival outcome were described. Multivariable analysis using Cox regression statistics were performed to identify significant prognostic variables affecting overall survival. Each variable were assigned points based on hazard ratios. A sum of the points led to a maximum score of 10. Patients were then categorized into low (0 point), intermediate (1 to 3 points) or high-risk group (4 points or above). Results: Demographics and treatment outcome of patients are shown in Table 1 & 2. There were 1277 adult patients, diagnosed with AML where 86.5% (n= 1106) of them were non M3 AML. Out of these, 908 patients (82.2%) received intensive chemotherapy treatment. Median age of diagnosis was 45 years. The remission post induction rate was 64.3% with induction death, refractory and relapse rate of 8.8%, 20.0% and 27.7% respectively. Median overall survival (OS) and Event Free Survival (EFS) time was 15 months and 12 months. The 3-year OS and EFS was 32.9% and 28.5% respectively. At the time of analysis, 66.1% of patients were dead (n=600) with disease progression being the main cause of death (n=416, 45.8%). Three year overall OS for patients who underwent allogeneic stem cell transplant (n=301, 33.1%) versus patients without transplantation were 53.7 % versus 22.0 % (HR 2.597, p <0.001). Cumulative incidence of relapsed and non-relapse mortality for transplant patients, shown in Figure 1 were 27.5% and 22.1%. Multivariate analysis in Table 3 showed that age 60 years old and above, male gender, white cell count more than 100 x 109 /L ,relapsed less than 12 months of treatment, refractory state after induction and high risk genetic group (based on EuropeanLeukemiaNet/Medical Research Council risk stratification by genetics) are prognostic factors associated with worse OS and EFS. The information was used to develop a 10 point prognostic index based on calculation described in Table 3. Overall survival decreased with each additional index point. When stratified according to risk group, the 3 year OS for low risk, intermediate risk and high risk group was 53.3%, 34.3% and 4.9% respectively. This is shown in Table 4 & Figure 2. Relapse rate was also lower in the low-risk group (8.8%), compared to intermediate-risk group (19.2%) and high-risk group (35.2%). Comparing transplant and non transplant cohort shown in Figure 3, there was no survival benefit in the low-risk group (58.6% vs 49.2%, p=0.122) but significant survival benefit in both intermediate-risk group (56.6% vs 23%, p<0.001) and adverse-risk group (13% vs 7%, p=0.002). Discussion/Conclusion: This is one of few survival studies that involved patients of different ethic groups in Asia (Malay, Chinese, Indian and native Borneo Sarawakians). Our results are comparable to data from large population based database such as US SEER and EURO CARE. This is the first prognostic index incorporating genetics, baseline characteristics and dynamic response, eg. refractory and/or relapsed post induction in non M3 AML. The results reaffirmed the importance of these factors in determining the clinical outcome and prognosis of patients with AML. When stratified using our 10 point prognostic index, our cohort of patients who is in low risk group has lower relapse rate and did not have significant survival benefit from allogeneic transplant compare to stratification using only the ELN/MRC genetic classification.(Table 5 & 6). In resource limited setting, measurable residual disease (MRD) monitoring and advanced genetic testing are difficult financially. This prognostic scoring index is an economical and practical alternative to guide physicians on treatment after induction therapy. However, it still needs to be validated by a larger cohort of patients in a prospective study. Disclosures No relevant conflicts of interest to declare.
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Boettcher, Steffen, Patrick Ziegler, and Markus G. Manz. "TLR Agonist Induced Cytokine Production in Human Multipotent Mesenchymal Stromal Cells: A Potential Mechanism How Hematopoiesis Is Enhanced during Generalized Inflammatory Conditions." Blood 110, no. 11 (November 16, 2007): 1411. http://dx.doi.org/10.1182/blood.v110.11.1411.1411.
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Abstract Toll-like receptors (TLRs) function as receptors for different conserved pathogen associated products as well as certain host derived molecules. TLRs are expressed in several hematopoietic and non-hematopoietic cells. Their activation plays a key role in innate and adaptive immune responses to infectious agents, as well as in the development of pathologic conditions like tissue damage and cancer. Human multipotent mesenchymal stromal cells (MSCs) have been shown to differentiate into various mesenchymal tissues such as bone, cartilage, and fat, as well as marrow and lymphoid organ stroma cells. Human MSCs are able to maintain CD34+ cells to some extent in vitro. Furthermore, it has been demonstrated that upon intra bone marrow transplantation into adult immunodeficient mice MSC derived cells support human hematopoiesis in vivo. We hypothesized that MSCs express TLRs and are capable to respond to TLR agonists by changing their cytokine expression pattern in order to more efficiently support hematopoiesis according to respective needs in inflammatory conditions. MSCs from human bone marrow, cord blood, and umbilical cord whartons jelly were cultured by plastic adherence in IMDM 20% FCS, 1–8M dexamethasone (only during first 3 weeks), expanded for 2 passages, and subsequently analyzed. MSCs expressed gene-transcripts for IL-6, IL-7, IL-11, IL-15, SCF, TPO, FLT3L, M-CSF, GM-CSF, LIF, and SDF-1, while G-CSF was rarely detectable. Consistently, respective cytokines were measured in supernatants at the following, declining levels (pg/ml): IL-6 (10000–10E6) > SDF-1 > IL-11 > M-CSF > IL-7 > LIF > SCF, whereas GM-CSF was rarely detectable, G-CSF, FLT3-L, and TPO were not detectable by ELISA. MSCs were further analyzed for expression of TLRs by semiquantitative RT-PCR. TLR 1, 3, 4, 5, 6, and 9 expression, but not TLR 2, 7, 8, and 10 expression was detectable. Compared to human conventional (BDCA-1+, CD14−, CD19−) and plasmacytoid (BDCA-4+,CD14−,CD19−) blood dendritic cells, MSCs expressed TLR-3 and TLR-4 at levels up to 2 log higher than did conventional DCs, while TLR 9 expression was low. Upon in vitro stimulation with LPS (TLR-4 agonist), MSCs produced previously undetectable G-CSF and GM-CSF, and M-CSF levels increased about 4 fold compared to untreated MSCs, whereas stimulation with CpG motifs (TLR-9 agonists) did not lead to changes in cytokine release detected in supernatants. In co-culture experiments using MSCs as a feeder layer for cord blood CD34+ cells, MSCs supported hematopoiesis and the development of myeloid cells. Importantly, MSC preconditioning with LPS led to an 1,7 fold increase in total hematopoietic cell number, while preconditioning with CpG had no measurable effect. These results demonstrate that MSCs express certain TLRs, and are capable to respond to pathogen associated molecules with an increase in secretion of hematopoiesis-relevant cytokines, and thus reveal a potential mechanism how hematopoiesis is enhanced during generalized inflammatory conditions, supporting e.g. in case of gram-negative sepsis efficient innate immune responses.
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Komornicki, Tomasz, Rafał Wiśniewski, and Andrzej Miszczuk. "Delimitacja przygranicznych obszarów problemowych = The delimitation of problem border areas." Przegląd Geograficzny 91, no. 4 (2019): 467–86. http://dx.doi.org/10.7163/przg.2019.4.2.
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While border areas are usually perceived as peripheral in nature, denoting only a limited level of economic development, it is clear that a border location might also be in a position to offer measurable benefit. In that context, work described here in relation to Poland has focused in on: (1) the delimitation of border areas; and (2) an identification and subdivision of units into those whose location by a state border brings either positive or negative economic consequences. The criterion applied most often in designating border areas is administrative (cf. Kałuski, 1990), with different hierarchical levels referred to (e.g. the NUTS 3 where pursuit of the EU policy on Territorial Cooperation is concerned; or LAU 2 where the need is to designate areas characterised by small-scale border traffic, with account then taken of the criterion of distance of a given administrative unit from the border). Alongside the administrative, a second main criterion relates simply to physical distance from a border, and usually gains application in denoting a zone of particularly intensive scrutiny by the Border Guard and other state services such as the Customs Administration (e.g. in the United States). Use of this criterion actually does much to hinder scientific research, given the lack of concordance with units of administration. Neither of the divisions referred to above embraces real functional linkages, while the real-life zone of impact of a border is likely to be indicated by just such linkages, of a socioeconomic nature, and specific in the sense that other parts of a country do not manifest them (Węcławowicz et al., 2006). Such linkages would seem to offer a basis to determine, first, if border areas actually exist at all, and, second, how they can be delimited in a detailed way, by reference to multiple criteria. It is certain that a key aspect is involved here, as the attempt is made to set the benefits of a border location against the “non-benefits”. But it is clear that attention also needs to be paid to the configuration of internal interactions, as aspects of a border location become all the more unfavourable the more peripherally a given unit is located. Ultimately, it is possible to indicate which border areas are actually problem areas, and to set these apart from other areas by a border whose geographical position ensures that a border represents no barrier to development and/or does not determine peripheral status. For the above reasons, the work presented here does indeed propose a delimitation based on real economic linkage (levels of export), as well as the degree to which regional centres are accessible from the given area. The first stage of the delimitation procedure thus takes in the designation of a border area formed from a belt of Polish communes (LAU 2) “two deep”. A second stage then sees elimination from this set of those units with a favourable location vis-à-vis the nearest regional centre (s), it being assumed that the proximity of these centres helps even out any potentially negative impact of the border; as well as with a high value for the statistic regarding the value of exports to the neighbouring country (the assumption then being that such units benefit from a border location, rather than suffering as a result of it). Units left behind following the application of this procedure were deemed to be border communes of problem status, potentially in need of support if they are to develop. In the event, such units are found to be located primarily along Poland’s borders with the Russian Federation, Lithuania, Belarus and Slovakia (as opposed to Germany, the Czech Republic and Ukraine). Unsurprisingly, it is communes by the Polish-German border that are seen to benefit most from their location. The authors set other divisions and classifications already in effect against the proposal for delimitation which is offered here, along with relevant recommendations for the development of regional policy.
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Fouquet, Guillemette, Susanna Schraen, Jean-Luc Faucompré, Lionel Karlin, Margaret Macro, Cyrille Hulin, Brigitte Onraed, et al. "Hevylite® to Monitor Response to Therapy in Multiple Myeloma." Blood 124, no. 21 (December 6, 2014): 2021. http://dx.doi.org/10.1182/blood.v124.21.2021.2021.
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Abstract Background. Protein electrophoresis and immunofixation in the serum (SPEP - SIF) and urine (UPEP – UIF) have been routinely used for decades for characterizing and quantifying the M protein in Multiple Myeloma (MM). However, these techniques are notoriously tarnished with inaccuracy, despite improvements in recent years. The most important breakthrough in the field in recent years was the discovery of the Serum Free Light Chain Assay (sFLC), a routine quantitative and automated assay that measures kappa and lambda sFLC, however this was added to / rather than replaced traditional tests in the diagnostic armamentarium of MM. Recently, a new test quantifying paired clonal and non-clonal immunoglobulins (heavy/light chains HLC i.e. IgGκ/IgGλ) in serum was developed. Here we aim to assess the new HLC assays as tools to replace SPEP / IFE during MM patient monitoring Materials and methods. 110 Myeloma treated with pomalidomide and dexamethasone in two IFM studies (IFM 2009-02 in end stage RRMM and IFM 2010-02 in del17p and t(4;14) RRMM ) were included. The criteria for selection were that patients had measurable intact immunoglobulin myeloma according to IMWG criteria (M spike ≥10g/L), using serum and/or urine protein electrophoresis, with exclusion of patients solely measurable on UPEP and sFLC. All sera were collected centrally before initiation of treatment and sequentially every cycle until progression. Hevylite® (HLC) was measured in the biology laboratory of CHRU of Lille, France and results compared to traditional measurements. Along with SPEP, SIF, UPEP, UIF, and sFLC, we have also measured IgA HLC (IgA k and IgA l) and IgG (IgG k and IgG l) and the corresponding difference (clonal - non clonal) and ratio (clonal/non clonal). Results. Overall, 80% were measurable on SPEP with a median serum level of 31g/L (CI95% 19;42), and the remaining also had UPEP measurable myeloma with a median serum level of 0.66g/24h (CI95% 0.4;1.3). The median involved HLC level was 29.7g/L (CI95% 17.6;43.3), the median involved HLC difference clonal - non clonal was 28.8g/L (CI95% 15.6;42.7), the median involved HLC ratio clonal / non clonal was 51.9 (CI95% 18.3;203.9). Since all patients had a measurable intact immunoglobulin-based disease according to IMWG criteria, we have first confirmed that patients had also a measurable disease by HLC. All patients had an abnormal HLC ratio but one patient, who was measurable with an abnormal IgG L involved HLC test. Approximately 32% of patients had an M-spike below 20g/L and/or an electrophoretic migration in beta region meaning in the range of lack of sensitivity of the techniques used, all of whom had a measurable disease using involved HLC level and/or a measurable HLC ratio. We then sought to study the response rate according to HLC, and for that purpose we applied the exact same criteria as to the sFLC-based response criteria recommended by IMWG (e.g. normal ratio is CR and if abnormal ratio, then <50% reduction in the difference clonal – non clonal is SD, ≥50% - <90% reduction is PR, >90% reduction is VGPR). The ORR in the 2 studies as a whole using traditional measurements was 32%, including 29% PR rate, absence of CR, and 44% had SD (SD and MR). Using HLC, the ORR was 36%, including 26% PR rate and 4.0% CR, and 33% had SD (r² 0.823, p<.0001). Interestingly, 7 patients classified as SD with regular techniques, were progressive disease using HLC, anticipating a progression of Myeloma. Similarly, 5 patients classified as SD with regular techniques, were ≥PR using HLC. Conclusion. HLC is a new routine quantitative and automated assay that measures Immunoglobulin heavy chain/light chain pairs immunoassay, allowing diagnosis, prognosis and precise assessment of the response to treatment and disease progression in all cases with Myeloma treated with pomalidomide and dexamethasone in 2 different clinical trials. Our study indicates that HLC may be used as a replacement for traditional tests and may offer greater sensitivity in some instances. Furthermore, obviating the need for interpretation may standardize assessments of patients during trials. Future studies might confirm this data analysis in larger trials. Disclosures Karlin: Janssen: Honoraria; celgene: Consultancy, Honoraria; Sandoz: Consultancy. Hulin:Celgene: Honoraria. Stoppa:Celgene Jansen: Honoraria. Marit:Celgene, Janssen: Congress expenses Other.
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van der Velde, Y., G. H. de Rooij, and P. J. J. F. Torfs. "Catchment-scale non-linear groundwater-surface water interactions in densely drained lowland catchments." Hydrology and Earth System Sciences 13, no. 10 (October 14, 2009): 1867–85. http://dx.doi.org/10.5194/hess-13-1867-2009.
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Abstract. Freely discharging lowland catchments are characterized by a strongly seasonal contracting and expanding system of discharging streams and ditches. Due to this rapidly changing active channel network, discharge and solute transport cannot be modeled by a single characteristic travel path, travel time distribution, unit hydrograph, or linear reservoir. We propose a systematic spatial averaging approach to derive catchment-scale storage and discharge from point-scale water balances. The effects of spatial heterogeneity in soil properties, vegetation, and drainage network are lumped and described by a relation between groundwater storage and the spatial probability distribution of groundwater depths with measurable parameters. The model describes how, in lowland catchments, the catchment-scale flux from groundwater to surface water via various flow routes is affected by a changing active channel network, the unsaturated zone and surface ponding. We used observations of groundwater levels and catchment discharge of a 6.6 km2 Dutch watershed in combination with a high-resolution spatially distributed hydrological model to test the model approach. Good results were obtained when modeling hourly discharges for a period of eight years. The validity of the underlying assumptions still needs to be tested under different conditions and for catchments of various sizes. Nevertheless, at this stage the model can already improve monitoring efficiency of groundwater-surface water interactions.
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Caniato and Gasparella. "Discriminating People’s Attitude towards Building Physical Features in Sustainable and Conventional Buildings." Energies 12, no. 8 (April 13, 2019): 1429. http://dx.doi.org/10.3390/en12081429.
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At the present time, buildings technologies for residential constructions are essentially divided into two groups. The first one is associated to conventional techniques using concrete, masonry or in general heavyweight structures, while the second one is associated to timber, e.g., sustainable glulam, crosslam, etc. (lightweight structures). Technicians, scientist, designers and non-expert people have their own stereotyped ideas and attitudes, related to thermal and sound insulation, structural stability, fire resistance, service equipment, heating and cooling systems, etc. Nevertheless, for people who is not strongly related to both construction procedure studies, analysis, experiences or focuses, timber structures appear to be more comfortable, reliable and insulated. The need of investigating the role of non-physical and non-measurable parameters in affecting future inhabitants’ overall preconceptions related to new sustainable buildings is thus of paramount importance. The hypothesis that behavioral, physiological, past experiences and psychological factors can have a non-negligible role in determining the final user perception, interaction and adaptation to timber buildings has to be verified. For these reasons, an international survey was realized in order to investigate what individuals expect from these two different construction technologies. After focused statistical analysis, it could be demonstrated how geographical difference could influence results and that, for indoor comfort, stereotypes do exist for lightweight buildings in comparison to heavyweight ones, highlighting how timber construction are associated to thermal comfort and sensed as innovative even if there is no complete distrust in conventional ones. The influence of non-physical and non-measurable parameters is correlated to people’s attitudes.
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Wu, Yi-Long, Myung-Ju Ahn, Marina Chiara Garassino, Ji-Youn Han, Nobuyuki Katakami, Hye Ryun Kim, Rachel Hodge, et al. "CNS Efficacy of Osimertinib in Patients With T790M-Positive Advanced Non–Small-Cell Lung Cancer: Data From a Randomized Phase III Trial (AURA3)." Journal of Clinical Oncology 36, no. 26 (September 10, 2018): 2702–9. http://dx.doi.org/10.1200/jco.2018.77.9363.
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Purpose In patients with epidermal growth factor receptor ( EGFR) mutation–positive advanced non–small-cell lung cancer (NSCLC), there is an unmet need for EGFR–tyrosine kinase inhibitors with improved CNS penetration and activity against CNS metastases, either at initial diagnosis or time of progression. We report the first comparative evidence of osimertinib CNS efficacy versus platinum-pemetrexed from a phase III study (AURA3; ClinicalTrials.gov identifier: NCT02151981) in patients with EGFR T790M–positive advanced NSCLC who experience disease progression with prior EGFR–tyrosine kinase inhibitor treatment. Methods Patients with asymptomatic, stable CNS metastases were eligible for enrollment and were randomly assigned 2:1 to osimertinib 80 mg once daily or platinum-pemetrexed. A preplanned subgroup analysis was conducted in patients with measurable and/or nonmeasurable CNS lesions on baseline brain scan by blinded independent central neuroradiological review. The CNS evaluable for response set included only patients with one or more measurable CNS lesions. The primary objective for this analysis was CNS objective response rate (ORR). Results Of 419 patients randomly assigned to treatment, 116 had measurable and/or nonmeasurable CNS lesions, including 46 patients with measurable CNS lesions. At data cutoff (April 15, 2016), CNS ORR in patients with one or more measurable CNS lesions was 70% (21 of 30; 95% CI, 51% to 85%) with osimertinib and 31% (5 of 16; 95% CI, 11% to 59%) with platinum-pemetrexed (odds ratio, 5.13; 95% CI, 1.44 to 20.64; P = .015); the ORR was 40% (30 of 75; 95% CI, 29% to 52%) and 17% (7 of 41; 95% CI, 7% to 32%), respectively, in patients with measurable and/or nonmeasurable CNS lesions (odds ratio, 3.24; 95% CI, 1.33 to 8.81; P = .014). Median CNS duration of response in patients with measurable and/or nonmeasurable CNS lesions was 8.9 months (95% CI, 4.3 months to not calculable) for osimertinib and 5.7 months (95% CI, 4.4 to 5.7 months) for platinum-pemetrexed; median CNS progression-free survival was 11.7 months and 5.6 months, respectively (hazard ratio, 0.32; 95% CI, 0.15 to 0.69; P = .004). Conclusion Osimertinib demonstrated superior CNS efficacy versus platinum-pemetrexed in T790M-positive advanced NSCLC.
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van der Velde, Y., G. H. de Rooij, and P. J. J. F. Torfs. "Catchment-scale non-linear groundwater-surface water interactions in densely drained lowland catchments." Hydrology and Earth System Sciences Discussions 6, no. 3 (May 7, 2009): 3753–810. http://dx.doi.org/10.5194/hessd-6-3753-2009.
Full textAbstract:
Abstract. Freely discharging lowland catchments are characterized by a strong seasonal contracting and expanding system of discharging streams and ditches. Due to this rapidly changing active channel network, discharge and solute transport cannot be modeled by a single characteristic travel path, travel time distribution, unit hydrograph, or linear reservoir. We propose a systematic spatial averaging approach to derive catchment-scale storage and discharge from point-scale water balances. The effects of spatial heterogeneity in soil properties, vegetation and drainage network are lumped and described by a relation between groundwater storage and the spatial probability distribution of groundwater depths with measurable parameters. The model describes how in lowland catchments the catchment-scale flux from groundwater to surface water via various flow routes is affected by a changing active channel network, unsaturated-saturated zone interactions and surface ponding. We used observations of groundwater levels and catchment discharge of a 6.6 km2 Dutch watershed in combination with a high-resolution spatially distributed hydrological model to test the model approach. Good results were obtained when modeling hourly discharges for a period of eight years. The validity of the underlying assumptions still needs to be tested under different conditions and for catchments of various sizes. Nevertheless, at this stage the model can already improve monitoring efficiency of groundwater-surface water interactions.