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2,710 results on '"Seppala, A."'

153. Boc modifies the spectrum of holoprosencephaly in the absence of Gas1 function

Author

Maisa Seppala, Guilherme M. Xavier, Chen-Ming Fan, and Martyn T. Cobourne

Subjects
Boc, Sonic hedgehog, Gas1, Lobar holoprosencephaly, Cleft lip and palate, Apoptosis, Science, Biology (General), QH301-705.5
Abstract

Holoprosencephaly is a heterogeneous developmental malformation of the central nervous system characterized by impaired forebrain cleavage, midline facial anomalies and wide phenotypic variation. Indeed, microforms represent the mildest manifestation, associated with facial anomalies but an intact central nervous system. In many cases, perturbations in sonic hedgehog signaling are responsible for holoprosencephaly. Here, we have elucidated the contribution of Gas1 and an additional hedgehog co-receptor, Boc during early development of the craniofacial midline, by generating single and compound mutant mice. Significantly, we find Boc has an essential role in the etiology of a unique form of lobar holoprosencephaly that only occurs in conjunction with combined loss of Gas1. Whilst Gas1−/− mice have microform holoprosencephaly characterized by a single median maxillary central incisor, cleft palate and pituitary anomalies, Boc−/− mice have a normal facial midline. However, Gas1−/−; Boc−/− mutants have lobar holoprosencephaly associated with clefting of the lip, palate and tongue, secondary to reduced sonic hedgehog transduction in the central nervous system and face. Moreover, maxillary incisor development is severely disrupted in these mice, arresting prior to cellular differentiation as a result of apoptosis in the odontogenic epithelium. Thus, Boc and Gas1 retain an essential function in these tooth germs, independent of their role in midline development of the central nervous system and face. Collectively, this phenotype demonstrates both redundancy and individual requirements for Gas1 and Boc during sonic hedgehog transduction in the craniofacial midline and suggests BOC as a potential digenic locus for lobar holoprosencephaly in human populations.

Published
2014
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154. Single cell transcriptomics reveals distinct transcriptional responses to oxycodone and buprenorphine by iPSC-derived brain organoids from patients with opioid use disorder

Author

Ho, Ming-Fen, primary, Zhang, Cheng, additional, Moon, Irene, additional, Zhu, Xiujuan, additional, Coombes, Brandon J., additional, Biernacka, Joanna, additional, Skime, Michelle, additional, Oesterle, Tyler S., additional, Karpyak, Victor M., additional, Schmidt, Kristen, additional, Gliske, Kate, additional, Ngo, Quyen, additional, Skillon, Cedric, additional, Seppala, Marvin D., additional, Li, Hu, additional, and Weinshilboum, Richard M., additional

Published
2022
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156. Are higher antidepressant plasma concentrations associated with fall risk in older antidepressant users?

Author

Pronk, anouschka, primary, Poelgeest, Eveline van, additional, Seppala, Lotta, additional, Ploegmakers, Kim, additional, Stricker, B H, additional, Swart-Polinder, Karin, additional, Dijk, Suzanne van, additional, Oliai, Sadaf, additional, Groot, Lisette de, additional, Schoor, Natasja M. van, additional, Mathot, Ron, additional, and Velde, Nathalie van der, additional

Published
2022
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159. The Dance of the Foci

Author

Seppala-Holtzman, David

Abstract

It's well known that slicing a cone with a plane and then allowing the plane to rotate through all possible angles of inclination yields the conic sections. What paths then do the foci of these conics trace out as this cutting plane passes through the different angles? In this article, we derive formulae for these trajectories and generate the associated curves. Of particular interest is how they articulate when the conic shifts from ellipse to parabola to hyperbola.

Published
2010

162. Developing a Benchmark Tool for Sustainable Consumption: An Iterative Process

Author

Heiskanen, E., Timonen, P., Nissinen, A., Gronroos, J., Honkanen, A., Katajajuuri, J. -M, Kettunen, J., Kurppa, S., Makinen, T., Seppala, J., Silvenius, F., Virtanen, Y., and Voutilainen, P.

Abstract

This article presents the development process of a consumer-oriented, illustrative benchmarking tool enabling consumers to use the results of environmental life cycle assessment (LCA) to make informed decisions. LCA provides a wealth of information on the environmental impacts of products, but its results are very difficult to present concisely and in a way that is understandable to non-experts. A participatory co-development process was thus deemed necessary to create an easy-to-use presentation format. A brochure presenting the benchmarking tool was developed in an iterative process involving consumer focus groups, stakeholder workshops, and questionnaire-based feedback. The co-development process proved its value: in addition to learning what works and what does not, detailed suggestions on improved wording and figures were obtained, as well as a wealth of ideas for future applications. (Contains 3 figures and 3 footnotes.)

Published
2007
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164. Suppression of Filament Defects in Embedded 3D Printing

Author

Leanne M. Friedrich, Ross T. Gunther, and Jonathan E. Seppala

Subjects
General Materials Science
Abstract

Embedded 3D printing enables the manufacture of soft, intricate structures. In the technique, a nozzle is embedded into a viscoelastic support bath and extrudes filaments or droplets. While embedded 3D printing expands the printable materials space to low-viscosity fluids, it also presents new challenges. Filament cross-sections can be tall and narrow, have sharp edges, and have rough surfaces. Filaments can also rupture or contract due to capillarity, harming print fidelity. Through digital image analysis of in situ videos of the printing process and images of filaments just after printing, we probe the effects of ink and support rheology, print speeds, and interfacial tension on defects in individual filaments. Using model materials, we determine that if both the ink and support are water-based, the local viscosity ratio near the nozzle controls the filament shape. If the ink is slightly more viscous than the support, a round, smooth filament is produced. If the ink is oil-based and the support is water-based, the capillary number, or the product of the ink speed and support viscosity divided by the interfacial tension, controls the filament shape. To suppress contraction and rupture, the capillary number should be high, even though this leads to trade-offs in roughness and roundness. Still, inks at nonzero interfacial tension can be advantageous, since they lead to much rounder and smoother filaments than inks at zero interfacial tension with equivalent viscosity ratios.

Published
2022

165. Development of the ADFICE_IT Models for Predicting Falls and Recurrent Falls in Community-Dwelling Older Adults:Pooled Analyses of European Cohorts With Special Attention to Medication

Author

Bob van de Loo, Lotta J Seppala, Nathalie van der Velde, Stephanie Medlock, Michael Denkinger, Lisette CPGM de Groot, Rose-Anne Kenny, Frank Moriarty, Dietrich Rothenbacher, Bruno Stricker, André Uitterlinden, Ameen Abu-Hanna, Martijn W Heymans, Natasja van Schoor, Graduate School, Geriatrics, APH - Aging & Later Life, AMS - Amsterdam Movement Sciences, AMS - Ageing & Vitality, Medical Informatics, APH - Methodology, Epidemiology, Internal Medicine, Epidemiology and Data Science, and APH - Personalized Medicine

Subjects
Aging, Individual participant data, Fall-risk-increasing drugs, Prognosis, Risk Assessment, Nutritional Biology, Cohort Studies, Urinary Incontinence, Risk Factors, Humans, Independent Living, Prospective Studies, Geriatrics and Gerontology, Accidental falls, Aged, VLAG
Abstract

Background Use of fall prevention strategies requires detection of high-risk patients. Our goal was to develop prediction models for falls and recurrent falls in community-dwelling older adults and to improve upon previous models by using a large, pooled sample and by considering a wide range of candidate predictors, including medications. Methods Harmonized data from 2 Dutch (LASA, B-PROOF) and 1 German cohort (ActiFE Ulm) of adults aged ≥65 years were used to fit 2 logistic regression models: one for predicting any fall and another for predicting recurrent falls over 1 year. Model generalizability was assessed using internal–external cross-validation. Results Data of 5 722 participants were included in the analyses, of whom 1 868 (34.7%) endured at least 1 fall and 702 (13.8%) endured a recurrent fall. Positive predictors for any fall were: educational status, depression, verbal fluency, functional limitations, falls history, and use of antiepileptics and drugs for urinary frequency and incontinence; negative predictors were: body mass index (BMI), grip strength, systolic blood pressure, and smoking. Positive predictors for recurrent falls were: educational status, visual impairment, functional limitations, urinary incontinence, falls history, and use of anti-Parkinson drugs, antihistamines, and drugs for urinary frequency and incontinence; BMI was a negative predictor. The average C-statistic value was 0.65 for the model for any fall and 0.70 for the model for recurrent falls. Conclusion Compared with previous models, the model for recurrent falls performed favorably while the model for any fall performed similarly. Validation and optimization of the models in other populations are warranted.

Published
2022
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167. Fall-Risk-Increasing Drugs: A Systematic Review and Meta-Analysis: II. Psychotropics

Author

Blain, Hubert, Bousquet, Jean, Bucht, Gösta, Caballero-Mora, Maria Angeles, van der Cammen, Tischa, Eklund, Patrik, Emmelot-Vonk, Marielle, Gustafson, Yngve, Hartikainen, Sirpa, Kenny, Rose Anne, Laflamme, Lucie, Landi, Francesco, Masud, Tahir, O'Byrne-Maguire, Irene, Petrovic, Mirko, Rodriguez, Leocadio, Seppälä, Lotta, Svensson, Olle, Szczerbińska, Katarzyna, Thaler, Heinrich, van der Velde, Nathalie, Seppala, Lotta J., Wermelink, Anne M.A.T., de Vries, Max, Ploegmakers, Kimberley J., van de Glind, Esther M.M., and Daams, Joost G.

Published
2018
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168. Fall-Risk-Increasing Drugs: A Systematic Review and Meta-analysis: III. Others

Author

Blain, Hubert, Bousquet, Jean, Bucht, Gösta, Caballero-Mora, Maria Angeles, van der Cammen, Tischa, Eklund, Patrik, Emmelot-Vonk, Marielle, Gustafson, Yngve, Hartikainen, Sirpa, Kenny, Rose Anne, Laflamme, Lucie, Landi, Francesco, Masud, Tahir, O'Byrne-Maguire, Irene, Petrovic, Mirko, Rodriguez, Leocadio, Seppälä, Lotta, Svensson, Olle, Szczerbińska, Katarzyna, Thaler, Heinrich, van der Velde, Nathalie, Seppala, Lotta J., van de Glind, Esther M.M., Daams, Joost G., Ploegmakers, Kimberley J., de Vries, Max, and Wermelink, Anne M.A.T.

Published
2018
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169. Fall-Risk-Increasing Drugs: A Systematic Review and Meta-Analysis: I. Cardiovascular Drugs

Author

Blain, Hubert, Bousquet, Jean, Bucht, Gösta, Caballero-Mora, Maria Angeles, van der Cammen, Tischa, Eklund, Patrik, Emmelot-Vonk, Marielle, Gustafson, Yngve, Hartikainen, Sirpa, Kenny, Rose Anne, Laflamme, Lucie, Landi, Francesco, Masud, Tahir, O'Byrne-Maguire, Irene, Petrovic, Mirko, Rodriguez, Leocadio, Seppälä, Lotta, Svensson, Olle, Szczerbińska, Katarzyna, Thaler, Heinrich, van der Velde, Nathalie, de Vries, Max, Seppala, Lotta J., Daams, Joost G., and van de Glind, Esther M.M.

Published
2018
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170. Observations on Student Misconceptions--A Case Study of the Build-Heap Algorithm

Author

Seppala, Otto, Malmi, Lauri, and Korhonen, Ari

Abstract

Data structures and algorithms are core issues in computer programming. However, learning them is challenging for most students and many of them have various types of misconceptions on how algorithms work. In this study, we discuss the problem of identifying misconceptions on the principles of how algorithms work. Our context is algorithm simulation exercises, where students simulate the steps of a given algorithm by manipulating data structure visualizations on a computer screen by using a mouse. Thus, contrasting to "typical" data structures and algorithms courses, these exercises are designed to work on an abstraction level higher than that of the actual implementation. We have analyzed the recorded simulation sequences to infer existing misconceptions from students' answers, and then implemented the corresponding variations of the target algorithm to find out how many of students' answers consistently follow each variation. The results suggest that many students are aware of the ultimate goal of the algorithm but have not studied the algorithm itself well enough. This often leads to different misconceptions that can be modeled and recognized using our approach. The results presented here concern the Build-Heap algorithm, but the approach is of general value. (Contains 1 figure, 1 table and 4 notes.)

Published
2006
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173. Sanctions Russia

Author

Seppala, Oscari

Subjects
Russian Invasion of Ukraine, 2022- -- Economic aspects, Financial institutions -- Laws, regulations and rules, Bank deposits -- Laws, regulations and rules, Sanctions (International law) -- Evaluation, Government regulation, Business, international
Abstract

Sanctions, negative effective measures, which has been set to Russia are to be updated, expanded as well as practices are to become more precise. The most recent sanctions are implementing [...]

Published
2022

178. Simulated filament shapes in embedded 3D printing

Author

Leanne Friedrich and Jonathan E. Seppala

Subjects
Materials science, Inkwell, business.industry, Yield surface, 3D printing, 02 engineering and technology, General Chemistry, 010402 general chemistry, 021001 nanoscience & nanotechnology, Condensed Matter Physics, 01 natural sciences, Article, 0104 chemical sciences, Surface tension, Protein filament, Rheology, Newtonian fluid, Composite material, 0210 nano-technology, business, Scaling
Abstract

Embedded 3D printing, wherein fluid inks are extruded into support baths, has enabled the manufacture of complex, custom structures ranging from cell-laden tissue analogues to soft robots. This method encompasses two techniques: embedded ink writing (EIW), where filaments are extruded, and embedded droplet printing (EDP), where droplets are suspended. Materials for embedded 3D printing can be Newtonian, but often both the ink and the support bath are yield stress fluids, following elastic behavior below the yield stress and shear-thinning, viscous behavior above the yield stress. The effect of surface tension on print quality has been debated, as inks have been printed into supports at high and low surface tensions. In order to guide material selection for embedded 3D printing and identify key scaling relationships that influence print quality, this study investigates the role of ink rheology, support rheology, and surface tension on the morphology of single filaments. Numerical simulations in OpenFOAM demonstrate that at low viscosities, surface tension controls the filament morphology. Where capillarity is suppressed, the ratio of the local ink and support viscosities and the shape of the yield surface in the support control the filament shape. Herschel-Bulkley support fluids (yield stress fluids) produce more stable, accurately positioned filaments than Newtonian supports. In the short term, non-zero surface tensions can suppress filament shape defects in EIW and are essential for producing droplets in EDP.

Published
2021
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182. P5. Single Cell Transcriptomics Reveals Distinct Transcriptional Response to Oxycodone and Buprenorphine by iPSC-Derived Brain Organoids From Patients With Opioid Use Disorder

Author

Ho, Ming-Fen, primary, Zhang, Cheng, additional, Moon, Irene, additional, Coombes, Brandon J., additional, Biernacka, Joanna, additional, Skime, Michelle K., additional, Oesterle, Tyler, additional, Karpyak, Victor, additional, Schmidt, Kristen, additional, Gliske, Kate, additional, Ngo, Quyen, additional, Skillon, Cedric, additional, Seppala, Marvin, additional, Li, Hu, additional, and Weinshilboum, Richard, additional

Published
2022
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183. P55. TRAIL Protein Levels are Associated With Response to Acamprosate Therapy in Alcohol Use Disorder: A Proteomics-Based Approach

Author

Atiq, Mazen, primary, Zhang, Cheng, additional, Moon, Irene, additional, Coombes, Brandon, additional, Biernacka, Joanna M., additional, Skime, Michelle K., additional, Choi, Doo-Sup, additional, Frye, Mark A., additional, Oesterle, Tyler, additional, Karpyak, Victor, additional, Schmidt, Kristen, additional, Gliske, Kate, additional, Ngo, Quyen, additional, Skillon, Cedric, additional, Seppala, Marvin, additional, Li, Hu, additional, Ho, Ming-Fen, additional, and Weinshilboum, Richard, additional

Published
2022
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184. Microsatellite instability in young patients with rectal cancer:molecular findings and treatment response

Author

Zaborowski, Alexandra M., Abdile, Ahmed, Adamina, Michel, Aigner, Felix, d'Allens, Laura, Allmer, Caterina, Álvarez, Andrea, Anula, Rocio, Andric, Mihailo, Atallah, Sam, Bach, Simon, Bala, Miklosh, Barussaud, Marie, Bausys, Augustinas, Beggs, Andrew, Bellolio, Felipe, Bennett, Melissa-Rose, Berdinskikh, Anton, Bevan, Vicki, Biondo, Sebastiano, Bislenghi, Gabriele, Bludau, Marc, Brouwer, Nelleke, Brown, Carl, Bruns, Christiane, Buchanan, Daniel D., Buchwald, Pamela, Burger, Jacobus W. A., Burlov, Nikita, Campanelli, Michela, Capdepont, Maylis, Carvello, Michele, Chew, Hwee-Hoon, Christoforidis, Dimitri, Clark, David, Climent, Marta, Collinson, Rowan, Cologne, Kyle G., Contreras, Tomas, Croner, Roland, Daniels, Ian R., Dapri, Giovanni, Davies, Justin, Delrio, Paolo, Denost, Quentin, Deutsch, Michael, Dias, Andre, D'Hoore, André, Drozdov, Evgeniy, Duek, Daniel, Dunlop, Malcolm, Dziki, Adam, Edmundson, Aleksandra, Efetov, Sergey, El-Hussuna, Alaa, Elliot, Brodie, Emile, Sameh, Espin, Eloy, Evans, Martyn, Faes, Seraina, Faiz, Omar, Figueiredo, Nuno, Fleming, Fergal, Foppa, Caterina, Fowler, George, Frasson, Matteo, Forgan, Tim, Frizelle, Frank, Gadaev, Shamil, Gellona, Jose, Glyn, Tamara, Goran, Barisic, Greenwood, Emma, Guren, Marianne G., Guillon, Stephanie, Gutlic, Ida, Hahnloser, Dieter, Hampel, Heather, Hanly, Ann, Hasegawa, Hirotoshi, Iversen, Lene Hjerrild, Hill, Andrew, Hill, James, Hoch, Jiri, Hompes, Roel, Hurtado, Luis, Iaquinandi, Fabiano, Imbrasaite, Ugne, Islam, Rumana, Jafari, Mehrenah D., Salido, Andrea Jiménez, Jiménez Toscano, Marta, Kanemitsu, Yukihide, Karachun, Aleksei, Karimuddin, Ahmer A., Keller, Deborah S., Kelly, Justin, Kennelly, Rory, Khrykov, Gleb, Kocian, Peter, Koh, Cherry, Kok, Neils, Knight, Katrina A., Knol, Joep, Kontovounisios, Christos, Korner, Hartwig, Krivokapic, Zoran, Kronberger, Irmgard, Kroon, Hidde Maarten, Kryzauskas, Marius, Kural, Said, Kusters, Miranda, Lakkis, Zaher, Lankov, Timur, Larson, David, Lázár, György, Lee, Kai-Yin, Lee, Suk Hwan, Lefèvre, Jérémie H., Lepisto, Anna, Lieu, Christopher, Loi, Lynette, Lynch, Craig, Maillou-Martinaud, Helene, Maroli, Annalisa, Martin, Sean, Martling, Anna, Matzel, Klaus E., Mayol, Julio, McDermott, Frank, Meurette, Guillaume, Millan, Monica, Mitteregger, Martin, Moiseenko, Andrei, Monson, John R. T., Morarasu, Stefan, Moritani, Konosuke, Möslein, Gabriela, Munini, Martino, Nahas, Caio, Nahas, Sergio, Negoi, Ionut, Novikova, Anastasia, Ocares, Misael, Okabayashi, Koji, Olkina, Alexandra, Oñate-Ocaña, Luis, Otero, Jaime, Ozen, Cihan, Pace, Ugo, Julião, Guilherme Pagin São, Panaiotti, Lidiia, Panis, Yves, Papamichael, Demetris, Patel, Swati, Uriburu, Juan Carlos Patrón, Peng, Sze-Lin, Pera, Miguel, Perez, Rodrigo O., Petrov, Alexei, Pfeffer, Frank, Phang, Terry P, Poskus, Tomas, Pringle, Heather, Proud, David, Raguz, Ivana, Rama, Nuno, Rasheed, Shahnawaz, Raval, Manoj J., Rega, Daniela, Reissfelder, Christoph, Meneses, Juan Carlos Reyes, Ris, Frederic, Riss, Stefan, Rodriguez-Zentner, Homero, Roxburgh, Campbell S., Saklani, Avanish, Sammour, Tarik, Saraste, Deborah, Schneider, Martin, Seishima, Ryo, Sekulic, Aleksander, Seppala, Toni, Sheahan, Kieran, Shlomina, Alexandra, Sigismondo, Guiseppe, Singnomklao, Tongplaew, Siragusa, Leandro, Smart, Neil, Solis-Peña, Alejandro, Spinelli, Antonino, Staiger, Roxane D., Stamos, Michael J., Steele, Scott, Tan, Ker-Kan, Tanis, Pieter J., Tekkis, Paris, Teklay, Biniam, Tengku, Sabrina, Tsarkov, Petr, Turina, Matthias, Ulrich, Alexis, Vailati, Bruna B., van Harten, Meike, Verhoef, Cornelis, Warrier, Satish, Wexner, Steven, de Wilt, Hans, Weinberg, Benjamin A., Wells, Cameron, Wolthuis, Albert, Xynos, Evangelos, You, Nancy, Zakharenko, Alexander, Zeballos, Justino, Zhou, Jonathan, Winter, Des C., Surgery, Amsterdam Gastroenterology Endocrinology Metabolism, and CCA - Cancer biology and immunology

Subjects
Adult, Male, Adolescent, Rectal Neoplasms, Middle Aged, Survival Analysis, digestive system diseases, Neoadjuvant Therapy, Settore MED/18, Young Adult, Rectal Neoplasms/genetics, SDG 3 - Good Health and Well-being, Chemotherapy, Adjuvant, Recurrence, Humans, Surgery, Female, Microsatellite Instability, Neoplasm Invasiveness, 03.02. Klinikai orvostan, Age of Onset, Retrospective Studies
Abstract

In this study of 400 patients with early-onset rectal cancer, 12.5 per cent demonstrated microsatellite instability (MSI). MSI was associated with a reduced likelihood of nodal positivity, an increased rate of pathological complete response, and improved disease-specific survival.

Published
2022
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185. Lawson Criterion for Ignition Exceeded in an Inertial Fusion Experiment

Author

Abu-Shawareb, H, Acree, R, Adams, P, Adams, J, Addis, B, Aden, R, Adrian, P, Afeyan, BB, Aggleton, M, Aghaian, L, Aguirre, A, Aikens, D, Akre, J, Albert, F, Albrecht, M, Albright, BJ, Albritton, J, Alcala, J, Alday, C, Alessi, DA, Alexander, N, Alfonso, J, Alfonso, N, Alger, E, Ali, SJ, Ali, ZA, Alley, WE, Amala, P, Amendt, PA, Amick, P, Ammula, S, Amorin, C, Ampleford, DJ, Anderson, RW, Anklam, T, Antipa, N, Appelbe, B, Aracne-Ruddle, C, Araya, E, Arend, M, Arnold, P, Arnold, T, Asay, J, Atherton, LJ, Atkinson, D, Atkinson, R, Auerbach, JM, Austin, B, Auyang, L, Awwal, AS, Ayers, J, Ayers, S, Ayers, T, Azevedo, S, Bachmann, B, Back, CA, Bae, J, Bailey, DS, Bailey, J, Baisden, T, Baker, KL, Baldis, H, Barber, D, Barberis, M, Barker, D, Barnes, A, Barnes, CW, Barrios, MA, Barty, C, Bass, I, Batha, SH, Baxamusa, SH, Bazan, G, Beagle, JK, Beale, R, Beck, BR, Beck, JB, Bedzyk, M, Beeler, RG, Behrendt, W, Belk, L, Bell, P, Belyaev, M, Benage, JF, Bennett, G, Benedetti, LR, Benedict, LX, Berger, R, Bernat, T, Bernstein, LA, Berry, B, Bertolini, L, Besenbruch, G, Betcher, J, Bettenhausen, R, Betti, R, Bezzerides, B, Bhandarkar, SD, Bickel, R, Biener, J, Biesiada, T, Bigelow, K, Bigelow-Granillo, J, Bigman, V, Bionta, RM, Birge, NW, Bitter, M, Black, AC, Bleile, R, Bleuel, DL, Bliss, E, Blue, B, Boehly, T, Boehm, K, Boley, CD, Bonanno, R, Bond, EJ, Bond, T, Bonino, MJ, Borden, M, Bourgade, J-L, Bousquet, J, Bowers, J, Bowers, M, Boyd, R, Bozek, A, Bradley, DK, Bradley, KS, Bradley, PA, Bradley, L, Brannon, L, Brantley, PS, Braun, D, Braun, T, Brienza-Larsen, K, Briggs, TM, Britten, J, Brooks, ED, Browning, D, Bruhn, MW, Brunner, TA, Bruns, H, Brunton, G, Bryant, B, Buczek, T, Bude, J, Buitano, L, Burkhart, S, Burmark, J, Burnham, A, Burr, R, Busby, LE, Butlin, B, Cabeltis, R, Cable, M, Cabot, WH, Cagadas, B, Caggiano, J, Cahayag, R, Caldwell, SE, Calkins, S, Callahan, DA, Calleja-Aguirre, J, Camara, L, Camp, D, Campbell, EM, Campbell, JH, Carey, B, Carey, R, Carlisle, K, Carlson, L, Carman, L, Carmichael, J, Carpenter, A, Carr, C, Carrera, JA, Casavant, D, Casey, A, Casey, DT, Castillo, A, Castillo, E, Castor, JI, Castro, C, Caughey, W, Cavitt, R, Celeste, J, Celliers, PM, Cerjan, C, Chandler, G, Chang, B, Chang, C, Chang, J, Chang, L, Chapman, R, Chapman, T, Chase, L, Chen, H, Chen, K, Chen, L-Y, Cheng, B, Chittenden, J, Choate, C, Chou, J, Chrien, RE, Chrisp, M, Christensen, K, Christensen, M, Christopherson, AR, Chung, M, Church, JA, Clark, A, Clark, DS, Clark, K, Clark, R, Claus, L, Cline, B, Cline, JA, Cobble, JA, Cochrane, K, Cohen, B, Cohen, S, Collette, MR, Collins, G, Collins, LA, Collins, TJB, Conder, A, Conrad, B, Conyers, M, Cook, AW, Cook, D, Cook, R, Cooley, JC, Cooper, G, Cope, T, Copeland, SR, Coppari, F, Cortez, J, Cox, J, Crandall, DH, Crane, J, Craxton, RS, Cray, M, Crilly, A, Crippen, JW, Cross, D, Cuneo, M, Cuotts, G, Czajka, CE, Czechowicz, D, Daly, T, Danforth, P, Darbee, R, Darlington, B, Datte, P, Dauffy, L, Davalos, G, Davidovits, S, Davis, P, Davis, J, Dawson, S, Day, RD, Day, TH, Dayton, M, Deck, C, Decker, C, Deeney, C, DeFriend, KA, Deis, G, Delamater, ND, Delettrez, JA, Demaret, R, Demos, S, Dempsey, SM, Desjardin, R, Desjardins, T, Desjarlais, MP, Dewald, EL, DeYoreo, J, Diaz, S, Dimonte, G, Dittrich, TR, Divol, L, Dixit, SN, Dixon, J, Dodd, ES, Dolan, D, Donovan, A, Donovan, M, Döppner, T, Dorrer, C, Dorsano, N, Douglas, MR, Dow, D, Downie, J, Downing, E, Dozieres, M, Draggoo, V, Drake, D, Drake, RP, Drake, T, Dreifuerst, G, DuBois, DF, DuBois, PF, Dunham, G, Dylla-Spears, R, Dymoke-Bradshaw, AKL, Dzenitis, B, Ebbers, C, Eckart, M, Eddinger, S, Eder, D, Edgell, D, Edwards, MJ, Efthimion, P, Eggert, JH, Ehrlich, B, Ehrmann, P, Elhadj, S, Ellerbee, C, Elliott, NS, Ellison, CL, Elsner, F, Emerich, M, Engelhorn, K, England, T, English, E, Epperson, P, Epstein, R, Erbert, G, Erickson, MA, Erskine, DJ, Erlandson, A, Espinosa, RJ, Estes, C, Estabrook, KG, Evans, S, Fabyan, A, Fair, J, Fallejo, R, Farmer, N, Farmer, WA, Farrell, M, Fatherley, VE, Fedorov, M, Feigenbaum, E, Feit, M, Ferguson, W, Fernandez, JC, Fernandez-Panella, A, Fess, S, Field, JE, Filip, CV, Fincke, JR, Finn, T, Finnegan, SM, Finucane, RG, Fischer, M, Fisher, A, Fisher, J, Fishler, B, Fittinghoff, D, Fitzsimmons, P, Flegel, M, Flippo, KA, Florio, J, Folta, J, Folta, P, Foreman, LR, Forrest, C, Forsman, A, Fooks, J, Foord, M, Fortner, R, Fournier, K, Fratanduono, DE, Frazier, N, Frazier, T, Frederick, C, Freeman, MS, Frenje, J, Frey, D, Frieders, G, Friedrich, S, Froula, DH, Fry, J, Fuller, T, Gaffney, J, Gales, S, Le Galloudec, B, Le Galloudec, KK, Gambhir, A, Gao, L, Garbett, WJ, Garcia, A, Gates, C, Gaut, E, Gauthier, P, Gavin, Z, Gaylord, J, Geissel, M, Génin, F, Georgeson, J, Geppert-Kleinrath, H, Geppert-Kleinrath, V, Gharibyan, N, Gibson, J, Gibson, C, Giraldez, E, Glebov, V, Glendinning, SG, Glenn, S, Glenzer, SH, Goade, S, Gobby, PL, Goldman, SR, Golick, B, Gomez, M, Goncharov, V, Goodin, D, Grabowski, P, Grafil, E, Graham, P, Grandy, J, Grasz, E, Graziani, F, Greenman, G, Greenough, JA, Greenwood, A, Gregori, G, Green, T, Griego, JR, Grim, GP, Grondalski, J, Gross, S, Guckian, J, Guler, N, Gunney, B, Guss, G, Haan, S, Hackbarth, J, Hackel, L, Hackel, R, Haefner, C, Hagmann, C, Hahn, KD, Hahn, S, Haid, BJ, Haines, BM, Hall, BM, Hall, C, Hall, GN, Hamamoto, M, Hamel, S, Hamilton, CE, Hammel, BA, Hammer, JH, Hampton, G, Hamza, A, Handler, A, Hansen, S, Hanson, D, Haque, R, Harding, D, Harding, E, Hares, JD, Harris, DB, Harte, JA, Hartouni, EP, Hatarik, R, Hatchett, S, Hauer, AA, Havre, M, Hawley, R, Hayes, J, Hayes, S, Hayes-Sterbenz, A, Haynam, CA, Haynes, DA, Headley, D, Heal, A, Heebner, JE, Heerey, S, Heestand, GM, Heeter, R, Hein, N, Heinbockel, C, Hendricks, C, Henesian, M, Heninger, J, Henrikson, J, Henry, EA, Herbold, EB, Hermann, MR, Hermes, G, Hernandez, JE, Hernandez, VJ, Herrmann, MC, Herrmann, HW, Herrera, OD, Hewett, D, Hibbard, R, Hicks, DG, Hill, D, Hill, K, Hilsabeck, T, Hinkel, DE, Ho, DD, Ho, VK, Hoffer, JK, Hoffman, NM, Hohenberger, M, Hohensee, M, Hoke, W, Holdener, D, Holdener, F, Holder, JP, Holko, B, Holunga, D, Holzrichter, JF, Honig, J, Hoover, D, Hopkins, D, Berzak Hopkins, L, Hoppe, M, Hoppe, ML, Horner, J, Hornung, R, Horsfield, CJ, Horvath, J, Hotaling, D, House, R, Howell, L, Hsing, WW, Hu, SX, Huang, H, Huckins, J, Hui, H, Humbird, KD, Hund, J, Hunt, J, Hurricane, OA, Hutton, M, Huynh, KH-K, Inandan, L, Iglesias, C, Igumenshchev, IV, Izumi, N, Jackson, M, Jackson, J, Jacobs, SD, James, G, Jancaitis, K, Jarboe, J, Jarrott, LC, Jasion, D, Jaquez, J, Jeet, J, Jenei, AE, Jensen, J, Jimenez, J, Jimenez, R, Jobe, D, Johal, Z, Johns, HM, Johnson, D, Johnson, MA, Gatu Johnson, M, Johnson, RJ, Johnson, S, Johnson, SA, Johnson, T, Jones, K, Jones, O, Jones, M, Jorge, R, Jorgenson, HJ, Julian, M, Jun, BI, Jungquist, R, Kaae, J, Kabadi, N, Kaczala, D, Kalantar, D, Kangas, K, Karasiev, VV, Karasik, M, Karpenko, V, Kasarky, A, Kasper, K, Kauffman, R, Kaufman, MI, Keane, C, Keaty, L, Kegelmeyer, L, Keiter, PA, Kellett, PA, Kellogg, J, Kelly, JH, Kemic, S, Kemp, AJ, Kemp, GE, Kerbel, GD, Kershaw, D, Kerr, SM, Kessler, TJ, Key, MH, Khan, SF, Khater, H, Kiikka, C, Kilkenny, J, Kim, Y, Kim, Y-J, Kimko, J, Kimmel, M, Kindel, JM, King, J, Kirkwood, RK, Klaus, L, Klem, D, Kline, JL, Klingmann, J, Kluth, G, Knapp, P, Knauer, J, Knipping, J, Knudson, M, Kobs, D, Koch, J, Kohut, T, Kong, C, Koning, JM, Koning, P, Konior, S, Kornblum, H, Kot, LB, Kozioziemski, B, Kozlowski, M, Kozlowski, PM, Krammen, J, Krasheninnikova, NS, Kraus, B, Krauser, W, Kress, JD, Kritcher, AL, Krieger, E, Kroll, JJ, Kruer, WL, Kruse, MKG, Kucheyev, S, Kumbera, M, Kumpan, S, Kunimune, J, Kustowski, B, Kwan, TJT, Kyrala, GA, Laffite, S, Lafon, M, LaFortune, K, Lahmann, B, Lairson, B, Landen, OL, Langenbrunner, J, Lagin, L, Land, T, Lane, M, Laney, D, Langdon, AB, Langer, SH, Langro, A, Lanier, NE, Lanier, TE, Larson, D, Lasinski, BF, Lassle, D, LaTray, D, Lau, G, Lau, N, Laumann, C, Laurence, A, Laurence, TA, Lawson, J, Le, HP, Leach, RR, Leal, L, Leatherland, A, LeChien, K, Lechleiter, B, Lee, A, Lee, M, Lee, T, Leeper, RJ, Lefebvre, E, Leidinger, J-P, LeMire, B, Lemke, RW, Lemos, NC, Le Pape, S, Lerche, R, Lerner, S, Letts, S, Levedahl, K, Lewis, T, Li, CK, Li, H, Li, J, Liao, W, Liao, ZM, Liedahl, D, Liebman, J, Lindford, G, Lindman, EL, Lindl, JD, Loey, H, London, RA, Long, F, Loomis, EN, Lopez, FE, Lopez, H, Losbanos, E, Loucks, S, Lowe-Webb, R, Lundgren, E, Ludwigsen, AP, Luo, R, Lusk, J, Lyons, R, Ma, T, Macallop, Y, MacDonald, MJ, MacGowan, BJ, Mack, JM, Mackinnon, AJ, MacLaren, SA, MacPhee, AG, Magelssen, GR, Magoon, J, Malone, RM, Malsbury, T, Managan, R, Mancini, R, Manes, K, Maney, D, Manha, D, Mannion, OM, Manuel, AM, Mapoles, E, Mara, G, Marcotte, T, Marin, E, Marinak, MM, Mariscal, C, Mariscal, DA, Mariscal, EF, Marley, EV, Marozas, JA, Marquez, R, Marshall, CD, Marshall, FJ, Marshall, M, Marshall, S, Marticorena, J, Martinez, D, Maslennikov, I, Mason, D, Mason, RJ, Masse, L, Massey, W, Masson-Laborde, P-E, Masters, ND, Mathisen, D, Mathison, E, Matone, J, Matthews, MJ, Mattoon, C, Mattsson, TR, Matzen, K, Mauche, CW, Mauldin, M, McAbee, T, McBurney, M, Mccarville, T, McCrory, RL, McEvoy, AM, McGuffey, C, Mcinnis, M, McKenty, P, McKinley, MS, McLeod, JB, McPherson, A, Mcquillan, B, Meamber, M, Meaney, KD, Meezan, NB, Meissner, R, Mehlhorn, TA, Mehta, NC, Menapace, J, Merrill, FE, Merritt, BT, Merritt, EC, Meyerhofer, DD, Mezyk, S, Mich, RJ, Michel, PA, Milam, D, Miller, C, Miller, D, Miller, DS, Miller, E, Miller, EK, Miller, J, Miller, M, Miller, PE, Miller, T, Miller, W, Miller-Kamm, V, Millot, M, Milovich, JL, Minner, P, Miquel, J-L, Mitchell, S, Molvig, K, Montesanti, RC, Montgomery, DS, Monticelli, M, Montoya, A, Moody, JD, Moore, AS, Moore, E, Moran, M, Moreno, JC, Moreno, K, Morgan, BE, Morrow, T, Morton, JW, Moses, E, Moy, K, Muir, R, Murillo, MS, Murray, JE, Murray, JR, Munro, DH, Murphy, TJ, Munteanu, FM, Nafziger, J, Nagayama, T, Nagel, SR, Nast, R, Negres, RA, Nelson, A, Nelson, D, Nelson, J, Nelson, S, Nemethy, S, Neumayer, P, Newman, K, Newton, M, Nguyen, H, Di Nicola, J-MG, Di Nicola, P, Niemann, C, Nikroo, A, Nilson, PM, Nobile, A, Noorai, V, Nora, R, Norton, M, Nostrand, M, Note, V, Novell, S, Nowak, PF, Nunez, A, Nyholm, RA, O'Brien, M, Oceguera, A, Oertel, JA, Okui, J, Olejniczak, B, Oliveira, J, Olsen, P, Olson, B, Olson, K, Olson, RE, Opachich, YP, Orsi, N, Orth, CD, Owen, M, Padalino, S, Padilla, E, Paguio, R, Paguio, S, Paisner, J, Pajoom, S, Pak, A, Palaniyappan, S, Palma, K, Pannell, T, Papp, F, Paras, D, Parham, T, Park, H-S, Pasternak, A, Patankar, S, Patel, MV, Patel, PK, Patterson, R, Patterson, S, Paul, B, Paul, M, Pauli, E, Pearce, OT, Pearcy, J, Pedrotti, B, Peer, A, Pelz, LJ, Penetrante, B, Penner, J, Perez, A, Perkins, LJ, Pernice, E, Perry, TS, Person, S, Petersen, D, Petersen, T, Peterson, DL, Peterson, EB, Peterson, JE, Peterson, JL, Peterson, K, Peterson, RR, Petrasso, RD, Philippe, F, Phipps, TJ, Piceno, E, Ping, Y, Pickworth, L, Pino, J, Plummer, R, Pollack, GD, Pollaine, SM, Pollock, BB, Ponce, D, Ponce, J, Pontelandolfo, J, Porter, JL, Post, J, Poujade, O, Powell, C, Powell, H, Power, G, Pozulp, M, Prantil, M, Prasad, M, Pratuch, S, Price, S, Primdahl, K, Prisbrey, S, Procassini, R, Pruyne, A, Pudliner, B, Qiu, SR, Quan, K, Quinn, M, Quintenz, J, Radha, PB, Rainer, F, Ralph, JE, Raman, KS, Raman, R, Rambo, P, Rana, S, Randewich, A, Rardin, D, Ratledge, M, Ravelo, N, Ravizza, F, Rayce, M, Raymond, A, Raymond, B, Reed, B, Reed, C, Regan, S, Reichelt, B, Reis, V, Reisdorf, S, Rekow, V, Remington, BA, Rendon, A, Requieron, W, Rever, M, Reynolds, H, Reynolds, J, Rhodes, J, Rhodes, M, Richardson, MC, Rice, B, Rice, NG, Rieben, R, Rigatti, A, Riggs, S, Rinderknecht, HG, Ring, K, Riordan, B, Riquier, R, Rivers, C, Roberts, D, Roberts, V, Robertson, G, Robey, HF, Robles, J, Rocha, P, Rochau, G, Rodriguez, J, Rodriguez, S, Rosen, M, Rosenberg, M, Ross, G, Ross, JS, Ross, P, Rouse, J, Rovang, D, Rubenchik, AM, Rubery, MS, Ruiz, CL, Rushford, M, Russ, B, Rygg, JR, Ryujin, BS, Sacks, RA, Sacks, RF, Saito, K, Salmon, T, Salmonson, JD, Sanchez, J, Samuelson, S, Sanchez, M, Sangster, C, Saroyan, A, Sater, J, Satsangi, A, Sauers, S, Saunders, R, Sauppe, JP, Sawicki, R, Sayre, D, Scanlan, M, Schaffers, K, Schappert, GT, Schiaffino, S, Schlossberg, DJ, Schmidt, DW, Schmitt, MJ, Schneider, DHG, Schneider, MB, Schneider, R, Schoff, M, Schollmeier, M, Schölmerich, M, Schroeder, CR, Schrauth, SE, Scott, HA, Scott, I, Scott, JM, Scott, RHH, Scullard, CR, Sedillo, T, Seguin, FH, Seka, W, Senecal, J, Sepke, SM, Seppala, L, Sequoia, K, Severyn, J, Sevier, JM, Sewell, N, Seznec, S, Shah, RC, Shamlian, J, Shaughnessy, D, Shaw, M, Shaw, R, Shearer, C, Shelton, R, Shen, N, Sherlock, MW, Shestakov, AI, Shi, EL, Shin, SJ, Shingleton, N, Shmayda, W, Shor, M, Shoup, M, Shuldberg, C, Siegel, L, Silva, FJ, Simakov, AN, Sims, BT, Sinars, D, Singh, P, Sio, H, Skulina, K, Skupsky, S, Slutz, S, Sluyter, M, Smalyuk, VA, Smauley, D, Smeltser, RM, Smith, C, Smith, I, Smith, J, Smith, L, Smith, R, Sohn, R, Sommer, S, Sorce, C, Sorem, M, Soures, JM, Spaeth, ML, Spears, BK, Speas, S, Speck, D, Speck, R, Spears, J, Spinka, T, Springer, PT, Stadermann, M, Stahl, B, Stahoviak, J, Stanton, LG, Steele, R, Steele, W, Steinman, D, Stemke, R, Stephens, R, Sterbenz, S, Sterne, P, Stevens, D, Stevers, J, Still, CB, Stoeckl, C, Stoeffl, W, Stolken, JS, Stolz, C, Storm, E, Stone, G, Stoupin, S, Stout, E, Stowers, I, Strauser, R, Streckart, H, Streit, J, Strozzi, DJ, Suratwala, T, Sutcliffe, G, Suter, LJ, Sutton, SB, Svidzinski, V, Swadling, G, Sweet, W, Szoke, A, Tabak, M, Takagi, M, Tambazidis, A, Tang, V, Taranowski, M, Taylor, LA, Telford, S, Theobald, W, Thi, M, Thomas, A, Thomas, CA, Thomas, I, Thomas, R, Thompson, IJ, Thongstisubskul, A, Thorsness, CB, Tietbohl, G, Tipton, RE, Tobin, M, Tomlin, N, Tommasini, R, Toreja, AJ, Torres, J, Town, RPJ, Townsend, S, Trenholme, J, Trivelpiece, A, Trosseille, C, Truax, H, Trummer, D, Trummer, S, Truong, T, Tubbs, D, Tubman, ER, Tunnell, T, Turnbull, D, Turner, RE, Ulitsky, M, Upadhye, R, Vaher, JL, VanArsdall, P, VanBlarcom, D, Vandenboomgaerde, M, VanQuinlan, R, Van Wonterghem, BM, Varnum, WS, Velikovich, AL, Vella, A, Verdon, CP, Vermillion, B, Vernon, S, Vesey, R, Vickers, J, Vignes, RM, Visosky, M, Vocke, J, Volegov, PL, Vonhof, S, Von Rotz, R, Vu, HX, Vu, M, Wall, D, Wall, J, Wallace, R, Wallin, B, Walmer, D, Walsh, CA, Walters, CF, Waltz, C, Wan, A, Wang, A, Wang, Y, Wark, JS, Warner, BE, Watson, J, Watt, RG, Watts, P, Weaver, J, Weaver, RP, Weaver, S, Weber, CR, Weber, P, Weber, SV, Wegner, P, Welday, B, Welser-Sherrill, L, Weiss, K, Widmann, K, Wheeler, GF, Whistler, W, White, RK, Whitley, HD, Whitman, P, Wickett, ME, Widmayer, C, Wiedwald, J, Wilcox, R, Wilcox, S, Wild, C, Wilde, BH, Wilde, CH, Wilhelmsen, K, Wilke, MD, Wilkens, H, Wilkins, P, Wilks, SC, Williams, EA, Williams, GJ, Williams, W, Williams, WH, Wilson, DC, Wilson, B, Wilson, E, Wilson, R, Winters, S, Wisoff, J, Wittman, M, Wolfe, J, Wong, A, Wong, KW, Wong, L, Wong, N, Wood, R, Woodhouse, D, Woodruff, J, Woods, DT, Woods, S, Woodworth, BN, Wooten, E, Wootton, A, Work, K, Workman, JB, Wright, J, Wu, M, Wuest, C, Wysocki, FJ, Xu, H, Yamaguchi, M, Yang, B, Yang, ST, Yatabe, J, Yeamans, CB, Yee, BC, Yi, SA, Yin, L, Young, B, Young, CS, Young, CV, Young, P, Youngblood, K, Zacharias, R, Zagaris, G, Zaitseva, N, Zaka, F, Ze, F, Zeiger, B, Zika, M, Zimmerman, GB, Zobrist, T, Zuegel, JD, Zylstra, AB, Indirect Drive ICF Collaboration, Collaboration, Indirect Drive ICF, AWE Plc, Lawrence Livermore National Laboratory, and U.S Department of Energy

Subjects
General Physics, 02 Physical Sciences, General Physics and Astronomy, Indirect Drive ICF Collaboration, 01 Mathematical Sciences, 09 Engineering
Abstract

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion.

Published
2022

187. Experimenting with Mobile Learning in a University Environment.

Author

Alamaki, Harri and Seppala, Pauliina

Abstract

This article describes a mobile learning project, where mobile devices are used for educational activities. The article defines the word "mobility" from the educational point of view. The authors present experiences recorded while using mobile technology in teacher training and among students of forest resource. Two pilots were carried out at the Department of Home Economics and Craft Science and the Department of Forest Resource Management of the University of Helsinki. The idea of the pilot in home economics teacher training was that supervising teachers and trainee students should discuss and share their ideas about teaching methods and other topics through mobile devices and also using SMS-messaging and digital pictures as part of the supervision process. The use of digital pictures, which were delivered via the mobile device, was surprisingly successful. The students of forest resources used mobile technology to deliver textual and pictorial material from forests. The goal of these innovative pilot projects is to create flexible teaching solutions that will enable users of all kinds of devices to access information, and to support learning in a variety of ways. (Contains 11 references.) (Author)

Published
2002

188. Utilization of poly(methyl methacrylate) – carbon nanotube and polystyrene – carbon nanotube in situ polymerized composites as masterbatches for melt mixing

Author

M. Lahelin, M. Annala, and J. Seppala

Subjects
Polymer composites, Nanocomposites, Material testing, Tailor-made polymers, Carbon nanotubes, Materials of engineering and construction. Mechanics of materials, TA401-492, Chemical technology, TP1-1185
Abstract

Carbon nanotubes (CNTs) were melt mixed directly or by using an in situ polymerized masterbatch into a matrix polymer, polystyrene (PS) or poly(methyl methacrylate) (PMMA). The mechanical properties of the composites were mostly determined by the amount of CNTs, and not by the use of directly melt mixed CNTs or the use of the masterbatch. In contrast, the electrical resistivity of the composites was dependent on the manner in which the CNTs were added to the matrix polymer. When there was increased interfacial adhesion between the components, as for PS and the CNTs, the use of directly melt mixed CNTs gave better resistivity results. Without strong interactions between the CNTs and the matrix, as with PMMA and CNTs, the use of a tailored masterbatch had a significant effect on properties of the final composites. The molecular weight and viscosity of masterbatches can be varied and when the PMMA-masterbatch had optimized viscosity with respect to the PMMA matrix, electrical resistivity of the final composites decreased noticeably.

Published
2012
Full Text
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189. Constructing Quality. European University Adult and Continuing Education.

Author

Seppala, Kari and Davies, Pat

Abstract

Experiences from six European projects suggest that adult and continuing education (ACE) differs from mainstream university provision in several ways: (1) definition of university ACE; (2) different organization; (3) needs of internal and external clients; and (4) emphasis on project over course work. Quality considerations include motivation for quality projects, aims and objectives, and choice of quality models. (SK)

Published
2001

190. Converging on the Eye of God

Author

Seppala-Holtzman, David N., Rangel, Francisco R., Colligan, J. Kevin, Kalman, Dan, and Stallings, Virginia

Published
2009

192. An Automated Disruption-Tolerant Key Management Framework for Critical Systems

Author

Edgar, Thomas, Edgar, Thomas, Ashok, Aditya, Seppala, Garret, Choi, Eric, Arthur-Durett, Kristine, Engels, Matt, Gentz, Reinhard, Peisert, Sean, Edgar, Thomas, Edgar, Thomas, Ashok, Aditya, Seppala, Garret, Choi, Eric, Arthur-Durett, Kristine, Engels, Matt, Gentz, Reinhard, and Peisert, Sean

Abstract

Key management is critical to secure operation. Distributed control systems, such as Supervisory Control and Data Acquisition (SCADA) systems, have unique operational requirements that make conventional key management solutions less effectiveand burdensome. This paper pres-ents a novel Kerberos-based framework for automated, disruption-tolerant key management for control system environments. Experimental tests and their results are presented to quantify the expected performance overhead of this approach. Additionally, Zeek sensor analytics are presented to aid in monitoring the health and security of the key management framework operation.

Published
2022

193. Medication reviews and deprescribing as a single intervention in falls prevention: a systematic review and meta-analysis

Author

Seppala, LJ, Kamkar, N, van Poelgeest, EP, Thomsen, K, Daams, JG, Ryg, J, Masud, T, Montero-Odasso, M, Hartikainen, S, Petrovic, M, van der Velde, N, Seppala, LJ, Kamkar, N, van Poelgeest, EP, Thomsen, K, Daams, JG, Ryg, J, Masud, T, Montero-Odasso, M, Hartikainen, S, Petrovic, M, and van der Velde, N

Abstract

BACKGROUND: our aim was to assess the effectiveness of medication review and deprescribing interventions as a single intervention in falls prevention. DESIGN: systematic review and meta-analysis. DATA SOURCES: Medline, Embase, Cochrane CENTRAL, PsycINFO until 28 March 2022. ELIGIBILITY CRITERIA: randomised controlled trials of older participants comparing any medication review or deprescribing intervention with usual care and reporting falls as an outcome. STUDY RECORDS: title/abstract and full-text screening by two reviewers. RISK OF BIAS: Cochrane Collaboration revised tool. DATA SYNTHESIS: results reported separately for different settings and sufficiently comparable studies meta-analysed. RESULTS: forty-nine heterogeneous studies were included. COMMUNITY: meta-analyses of medication reviews resulted in a risk ratio (RR) of 1.05 (95% confidence interval, 0.85-1.29, I2 = 0%, 3 studies(s)) for number of fallers, in an RR = 0.95 (0.70-1.27, I2 = 37%, 3 s) for number of injurious fallers and in a rate ratio (RaR) of 0.89 (0.69-1.14, I2 = 0%, 2 s) for injurious falls. HOSPITAL: meta-analyses assessing medication reviews resulted in an RR = 0.97 (0.74-1.28, I2 = 15%, 2 s) and in an RR = 0.50 (0.07-3.50, I2 = 72% %, 2 s) for number of fallers after and during admission, respectively. LONG-TERM CARE: meta-analyses investigating medication reviews or deprescribing plans resulted in an RR = 0.86 (0.72-1.02, I2 = 0%, 5 s) for number of fallers and in an RaR = 0.93 (0.64-1.35, I2 = 92%, 7 s) for number of falls. CONCLUSIONS: the heterogeneity of the interventions precluded us to estimate the exact effect of medication review and deprescribing as a single intervention. For future studies, more comparability is warranted. These interventions should not be implemented as a stand-alone strategy in falls prevention but included in multimodal strategies due to the multifactorial nature of falls.PROSPERO registration number: CRD42020218231.

Published
2022

194. Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

Author

Moller, P, Seppala, T, Dowty, JG, Haupt, S, Dominguez-Valentin, M, Sunde, L, Bernstein, I, Engel, C, Aretz, S, Nielsen, M, Capella, G, Evans, DG, Burn, J, Holinski-Feder, E, Bertario, L, Bonanni, B, Lindblom, A, Levi, Z, Macrae, F, Winship, I, Plazzer, J-P, Sijmons, R, Laghi, L, Della Valle, A, Heinimann, K, Half, E, Lopez-Koestner, F, Alvarez-Valenzuela, K, Scott, RJ, Katz, L, Laish, I, Vainer, E, Vaccaro, CA, Carraro, DM, Gluck, N, Abu-Freha, N, Stakelum, A, Kennelly, R, Winter, D, Rossi, BM, Greenblatt, M, Bohorquez, M, Sheth, H, Tibiletti, MG, Lino-Silva, LS, Horisberger, K, Portenkirchner, C, Nascimento, I, Rossi, NT, da Silva, LA, Thomas, H, Zarand, A, Mecklin, J-P, Pylvanainen, K, Renkonen-Sinisalo, L, Lepisto, A, Peltomaki, P, Therkildsen, C, Lindberg, LJ, Thorlacius-Ussing, O, von Knebel Doeberitz, M, Loeffler, M, Rahner, N, Steinke-Lange, V, Schmiegel, W, Vangala, D, Perne, C, Hueneburg, R, de Vargas, AF, Latchford, A, Gerdes, A-M, Backman, A-S, Guillen-Ponce, C, Snyder, C, Lautrup, CK, Amor, D, Palmero, E, Stoffel, E, Duijkers, F, Hall, MJ, Hampel, H, Williams, H, Okkels, H, Lubinski, J, Reece, J, Ngeow, J, Guillem, JG, Arnold, J, Wadt, K, Monahan, K, Senter, L, Rasmussen, LJ, van Hest, LP, Ricciardiello, L, Kohonen-Corish, MRJ, Ligtenberg, MJL, Southey, M, Aronson, M, Zahary, MN, Samadder, NJ, Poplawski, N, Hoogerbrugge, N, Morrison, PJ, James, P, Lee, G, Chen-Shtoyerman, R, Ankathil, R, Pai, R, Ward, R, Parry, S, Debniak, T, John, T, van Overeem Hansen, T, Caldes, T, Yamaguchi, T, Barca-Tierno, V, Garre, P, Cavestro, GM, Weitz, J, Redler, S, Buettner, R, Heuveline, V, Hopper, JL, Win, AK, Lindor, N, Gallinger, S, Le Marchand, L, Newcomb, PA, Figueiredo, J, Buchanan, DD, Thibodeau, SN, ten Broeke, SW, Hovig, E, Nakken, S, Pineda, M, Duenas, N, Brunet, J, Green, K, Lalloo, F, Newton, K, Crosbie, EJ, Mints, M, Tjandra, D, Neffa, F, Esperon, P, Kariv, R, Rosner, G, Pavicic, WH, Kalfayan, P, Torrezan, GT, Bassaneze, T, Martin, C, Moslein, G, Ahadova, A, Kloor, M, Sampson, JR, Jenkins, MA, Moller, P, Seppala, T, Dowty, JG, Haupt, S, Dominguez-Valentin, M, Sunde, L, Bernstein, I, Engel, C, Aretz, S, Nielsen, M, Capella, G, Evans, DG, Burn, J, Holinski-Feder, E, Bertario, L, Bonanni, B, Lindblom, A, Levi, Z, Macrae, F, Winship, I, Plazzer, J-P, Sijmons, R, Laghi, L, Della Valle, A, Heinimann, K, Half, E, Lopez-Koestner, F, Alvarez-Valenzuela, K, Scott, RJ, Katz, L, Laish, I, Vainer, E, Vaccaro, CA, Carraro, DM, Gluck, N, Abu-Freha, N, Stakelum, A, Kennelly, R, Winter, D, Rossi, BM, Greenblatt, M, Bohorquez, M, Sheth, H, Tibiletti, MG, Lino-Silva, LS, Horisberger, K, Portenkirchner, C, Nascimento, I, Rossi, NT, da Silva, LA, Thomas, H, Zarand, A, Mecklin, J-P, Pylvanainen, K, Renkonen-Sinisalo, L, Lepisto, A, Peltomaki, P, Therkildsen, C, Lindberg, LJ, Thorlacius-Ussing, O, von Knebel Doeberitz, M, Loeffler, M, Rahner, N, Steinke-Lange, V, Schmiegel, W, Vangala, D, Perne, C, Hueneburg, R, de Vargas, AF, Latchford, A, Gerdes, A-M, Backman, A-S, Guillen-Ponce, C, Snyder, C, Lautrup, CK, Amor, D, Palmero, E, Stoffel, E, Duijkers, F, Hall, MJ, Hampel, H, Williams, H, Okkels, H, Lubinski, J, Reece, J, Ngeow, J, Guillem, JG, Arnold, J, Wadt, K, Monahan, K, Senter, L, Rasmussen, LJ, van Hest, LP, Ricciardiello, L, Kohonen-Corish, MRJ, Ligtenberg, MJL, Southey, M, Aronson, M, Zahary, MN, Samadder, NJ, Poplawski, N, Hoogerbrugge, N, Morrison, PJ, James, P, Lee, G, Chen-Shtoyerman, R, Ankathil, R, Pai, R, Ward, R, Parry, S, Debniak, T, John, T, van Overeem Hansen, T, Caldes, T, Yamaguchi, T, Barca-Tierno, V, Garre, P, Cavestro, GM, Weitz, J, Redler, S, Buettner, R, Heuveline, V, Hopper, JL, Win, AK, Lindor, N, Gallinger, S, Le Marchand, L, Newcomb, PA, Figueiredo, J, Buchanan, DD, Thibodeau, SN, ten Broeke, SW, Hovig, E, Nakken, S, Pineda, M, Duenas, N, Brunet, J, Green, K, Lalloo, F, Newton, K, Crosbie, EJ, Mints, M, Tjandra, D, Neffa, F, Esperon, P, Kariv, R, Rosner, G, Pavicic, WH, Kalfayan, P, Torrezan, GT, Bassaneze, T, Martin, C, Moslein, G, Ahadova, A, Kloor, M, Sampson, JR, and Jenkins, MA

Abstract

OBJECTIVE: To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. METHODS: CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands. RESULTS: In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups. CONCLUSIONS: Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so.

Published
2022

195. Cancer Prevention with Resistant Starch in Lynch Syndrome Patients in the CAPP2-Randomized Placebo Controlled Trial: Planned 10-Year Follow-up

Author

Mathers, JC, Elliott, F, Macrae, F, Mecklin, J-P, Moslein, G, McRonald, FE, Bertario, L, Evans, DG, Gerdes, A-M, Ho, JWC, Lindblom, A, Morrison, PJ, Rashbass, J, Ramesar, RS, Seppala, TT, Thomas, HJW, Sheth, HJ, Pylvanainen, K, Reed, L, Borthwick, GM, Bishop, DT, Burn, J, Mathers, JC, Elliott, F, Macrae, F, Mecklin, J-P, Moslein, G, McRonald, FE, Bertario, L, Evans, DG, Gerdes, A-M, Ho, JWC, Lindblom, A, Morrison, PJ, Rashbass, J, Ramesar, RS, Seppala, TT, Thomas, HJW, Sheth, HJ, Pylvanainen, K, Reed, L, Borthwick, GM, Bishop, DT, and Burn, J

Abstract

The CAPP2 trial investigated the long-term effects of aspirin and resistant starch on cancer incidence in patients with Lynch syndrome (LS). Participants with LS were randomized double-blind to 30 g resistant starch (RS) daily or placebo for up to 4 years. We present long-term cancer outcomes based on the planned 10-year follow-up from recruitment, supplemented by National Cancer Registry data to 20 years in England, Wales, and Finland. Overall, 463 participants received RS and 455 participants received placebo. After up to 20 years follow-up, there was no difference in colorectal cancer incidence (n = 52 diagnosed with colorectal cancer among those randomized to RS against n = 53 on placebo) but fewer participants had non-colorectal LS cancers in those randomized to RS (n = 27) compared with placebo (n = 48); intention-to-treat (ITT) analysis [HR, 0.54; 95% confidence interval (CI), 0.33-0.86; P = 0.010]. In ITT analysis, allowing for multiple primary cancer diagnoses among participants by calculating incidence rate ratios (IRR) confirmed the protective effect of RS against non-colorectal cancer LS cancers (IRR, 0.52; 95% CI, 0.32-0.84; P = 0.0075). These effects are particularly pronounced for cancers of the upper GI tract; 5 diagnoses in those on RS versus 21 diagnoses on placebo. The reduction in non-colorectal cancer LS cancers was detectable in the first 10 years and continued in the next decade. For colorectal cancer, ITT analysis showed no effect of RS on colorectal cancer risk (HR, 0.92; 95% CI, 0.62-1.34; P = 0.63). There was no interaction between aspirin and RS treatments. In conclusion, 30 g daily RS appears to have a substantial protective effect against non-colorectal cancer cancers for patients with LS. PREVENTION RELEVANCE: Regular bowel screening and aspirin reduce colorectal cancer among patients with LS but extracolonic cancers are difficult to detect and manage. This study suggests that RS reduces morbidity associated with extracolonic

Published
2022

196. Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium

Author

Moller, Pal, Seppala, Toni, Dowty, James G., Haupt, Saskia, Dominguez-Valentin, Mev, Sunde, Lone, Bernstein, Inge, Engel, Christoph, Aretz, Stefan, Nielsen, Maartje, Capella, Gabriel, Evans, Dafydd Gareth, Burn, John, Holinski-Feder, Elke, Bertario, Lucio, Bonanni, Bernardo, Lindblom, Annika, Levi, Zohar, Macrae, Finlay, Winship, Ingrid, Plazzer, John-Paul, Sijmons, Rolf, Laghi, Luigi, Della Valle, Adriana, Heinimann, Karl, Half, Elizabeth, Lopez-Koestner, Francisco, Alvarez-Valenzuela, Karin, Scott, Rodney J., Katz, Lior, Laish, Ido, Vainer, Elez, Vaccaro, Carlos Alberto, Carraro, Dirce Maria, Gluck, Nathan, Abu-Freha, Naim, Stakelum, Aine, Kennelly, Rory, Winter, Des, Rossi, Benedito Mauro, Greenblatt, Marc, Bohorquez, Mabel, Sheth, Harsh, Tibiletti, Maria Grazia, Lino-Silva, Leonardo S., Horisberger, Karoline, Portenkirchner, Carmen, Nascimento, Ivana, Rossi, Norma Teresa, da Silva, Leandro Apolinario, Thomas, Huw, Zarand, Attila, Mecklin, Jukka-Pekka, Pylvanainen, Kirsi, Renkonen-Sinisalo, Laura, Lepisto, Anna, Peltomaki, Paivi, Therkildsen, Christina, Lindberg, Lars Joachim, Thorlacius-Ussing, Ole, von Knebel Doeberitz, Magnus, Loeffler, Markus, Rahner, Nils, Steinke-Lange, Verena, Schmiegel, Wolff, Vangala, Deepak, Perne, Claudia, Hueneburg, Robert, de Vargas, Aida Falcon, Latchford, Andrew, Gerdes, Anne-Marie, Backman, Ann-Sofie, Guillen-Ponce, Carmen, Snyder, Carrie, Lautrup, Charlotte K., Amor, David, Palmero, Edenir, Stoffel, Elena, Duijkers, Floor, Hall, Michael J., Hampel, Heather, Williams, Heinric, Okkels, Henrik, Lubinski, Jan, Reece, Jeanette, Ngeow, Joanne, Guillem, Jose G., Arnold, Julie, Wadt, Karin, Monahan, Kevin, Senter, Leigha, Rasmussen, Lene J., van Hest, Liselotte P., Ricciardiello, Luigi, Kohonen-Corish, Maija R. J., Ligtenberg, Marjolijn J. L., Southey, Melissa, Aronson, Melyssa, Zahary, Mohd N., Samadder, N. Jewel, Poplawski, Nicola, Hoogerbrugge, Nicoline, Morrison, Patrick J., James, Paul, Lee, Grant, Chen-Shtoyerman, Rakefet, Ankathil, Ravindran, Pai, Rish, Ward, Robyn, Parry, Susan, Debniak, Tadeusz, John, Thomas, van Overeem Hansen, Thomas, Caldes, Trinidad, Yamaguchi, Tatsuro, Barca-Tierno, Veronica, Garre, Pilar, Cavestro, Giulia Martina, Weitz, Juergen, Redler, Silke, Buettner, Reinhard, Heuveline, VincentZ, Hopper, John L., Win, Aung Ko, Lindor, Noralane, Gallinger, Steven, Le Marchand, Loic, Newcomb, Polly A., Figueiredo, Jane, Buchanan, Daniel D., Thibodeau, Stephen N., ten Broeke, Sanne W., Hovig, Eivind, Nakken, Sigve, Pineda, Marta, Duenas, Nuria, Brunet, Joan, Green, Kate, Lalloo, Fiona, Newton, Katie, Crosbie, Emma J., Mints, Miriam, Tjandra, Douglas, Neffa, Florencia, Esperon, Patricia, Kariv, Revital, Rosner, Guy, Pavicic, Walter Hernan, Kalfayan, Pablo, Torrezan, Giovana Tardin, Bassaneze, Thiago, Martin, Claudia, Moslein, Gabriela, Ahadova, Aysel, Kloor, Matthias, Sampson, Julian R., Jenkins, Mark A., Moller, Pal, Seppala, Toni, Dowty, James G., Haupt, Saskia, Dominguez-Valentin, Mev, Sunde, Lone, Bernstein, Inge, Engel, Christoph, Aretz, Stefan, Nielsen, Maartje, Capella, Gabriel, Evans, Dafydd Gareth, Burn, John, Holinski-Feder, Elke, Bertario, Lucio, Bonanni, Bernardo, Lindblom, Annika, Levi, Zohar, Macrae, Finlay, Winship, Ingrid, Plazzer, John-Paul, Sijmons, Rolf, Laghi, Luigi, Della Valle, Adriana, Heinimann, Karl, Half, Elizabeth, Lopez-Koestner, Francisco, Alvarez-Valenzuela, Karin, Scott, Rodney J., Katz, Lior, Laish, Ido, Vainer, Elez, Vaccaro, Carlos Alberto, Carraro, Dirce Maria, Gluck, Nathan, Abu-Freha, Naim, Stakelum, Aine, Kennelly, Rory, Winter, Des, Rossi, Benedito Mauro, Greenblatt, Marc, Bohorquez, Mabel, Sheth, Harsh, Tibiletti, Maria Grazia, Lino-Silva, Leonardo S., Horisberger, Karoline, Portenkirchner, Carmen, Nascimento, Ivana, Rossi, Norma Teresa, da Silva, Leandro Apolinario, Thomas, Huw, Zarand, Attila, Mecklin, Jukka-Pekka, Pylvanainen, Kirsi, Renkonen-Sinisalo, Laura, Lepisto, Anna, Peltomaki, Paivi, Therkildsen, Christina, Lindberg, Lars Joachim, Thorlacius-Ussing, Ole, von Knebel Doeberitz, Magnus, Loeffler, Markus, Rahner, Nils, Steinke-Lange, Verena, Schmiegel, Wolff, Vangala, Deepak, Perne, Claudia, Hueneburg, Robert, de Vargas, Aida Falcon, Latchford, Andrew, Gerdes, Anne-Marie, Backman, Ann-Sofie, Guillen-Ponce, Carmen, Snyder, Carrie, Lautrup, Charlotte K., Amor, David, Palmero, Edenir, Stoffel, Elena, Duijkers, Floor, Hall, Michael J., Hampel, Heather, Williams, Heinric, Okkels, Henrik, Lubinski, Jan, Reece, Jeanette, Ngeow, Joanne, Guillem, Jose G., Arnold, Julie, Wadt, Karin, Monahan, Kevin, Senter, Leigha, Rasmussen, Lene J., van Hest, Liselotte P., Ricciardiello, Luigi, Kohonen-Corish, Maija R. J., Ligtenberg, Marjolijn J. L., Southey, Melissa, Aronson, Melyssa, Zahary, Mohd N., Samadder, N. Jewel, Poplawski, Nicola, Hoogerbrugge, Nicoline, Morrison, Patrick J., James, Paul, Lee, Grant, Chen-Shtoyerman, Rakefet, Ankathil, Ravindran, Pai, Rish, Ward, Robyn, Parry, Susan, Debniak, Tadeusz, John, Thomas, van Overeem Hansen, Thomas, Caldes, Trinidad, Yamaguchi, Tatsuro, Barca-Tierno, Veronica, Garre, Pilar, Cavestro, Giulia Martina, Weitz, Juergen, Redler, Silke, Buettner, Reinhard, Heuveline, VincentZ, Hopper, John L., Win, Aung Ko, Lindor, Noralane, Gallinger, Steven, Le Marchand, Loic, Newcomb, Polly A., Figueiredo, Jane, Buchanan, Daniel D., Thibodeau, Stephen N., ten Broeke, Sanne W., Hovig, Eivind, Nakken, Sigve, Pineda, Marta, Duenas, Nuria, Brunet, Joan, Green, Kate, Lalloo, Fiona, Newton, Katie, Crosbie, Emma J., Mints, Miriam, Tjandra, Douglas, Neffa, Florencia, Esperon, Patricia, Kariv, Revital, Rosner, Guy, Pavicic, Walter Hernan, Kalfayan, Pablo, Torrezan, Giovana Tardin, Bassaneze, Thiago, Martin, Claudia, Moslein, Gabriela, Ahadova, Aysel, Kloor, Matthias, Sampson, Julian R., and Jenkins, Mark A.

Abstract

Objective To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. Methods CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands. Results In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups. Conclusions Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so.

Published
2022

197. Candidate genetic variants and antidepressant-related fall risk in middle-aged and older adults

Author

Pronk, A. C., Seppala, L. J., Trajanoska, K., Stringa, N., van de Loo, B., de Groot, L. C.P.G.M., van Schoor, N. M., Koskeridis, F., Markozannes, G., Ntzani, E., Uitterlinden, A. G., Rivadeneira, F., Stricker, B. H., van der Velde, N., Pronk, A. C., Seppala, L. J., Trajanoska, K., Stringa, N., van de Loo, B., de Groot, L. C.P.G.M., van Schoor, N. M., Koskeridis, F., Markozannes, G., Ntzani, E., Uitterlinden, A. G., Rivadeneira, F., Stricker, B. H., and van der Velde, N.

Abstract

Background Antidepressant use has been associated with increased fall risk. Antidepressant-related adverse drug reactions (e.g. orthostatic hypotension) depend partly on genetic variation. We hypothesized that candidate genetic polymorphisms are associated with fall risk in older antidepressant users. Methods The association between antidepressant use and falls was cross-sectionally investigated in a cohort of Dutch older adults by logistic regression analyses. In case of significant interaction product term of antidepressant use and candidate polymorphism, the association between the variant genotype and fall risk was assessed within antidepressant users and the association between antidepressant use and fall risk was investigated stratified per genotype. Secondly, a look-up of the candidate genes was performed in an existing genome-wide association study on drug-related falls in antidepressant users within the UK Biobank. In antidepressant users, genetic associations for our candidate polymorphisms for fall history were investigated. Results In antidepressant users(n = 566), for rs28371725 (CYP2D6*41) fall risk was decreased in TC/variant allele carriers compared to CC/non-variant allele carriers (OR = 0.45, 95% CI 0.26–0.80). Concerning rs1057910 (CYP2C9*3), fall risk was increased in CA/variant allele carriers compared to AA/non-variant allele carriers (OR = 1.95, 95% CI 1.17–3.27). Regarding, rs1045642 (ABCB1), fall risk was increased in AG/variant allele carriers compared to GG/non-variant allele carriers (OR = 1.69, 95% CI 1.07–2.69). Concerning the ABCB1-haplotype (rs1045642/rs1128503), fall risk was increased in AA-AA/variant allele carriers compared to GG-GG/non-variant allele carriers (OR = 1.86, 95% CI 1.05–3.29). In the UK Biobank, in antidepressant users(n = 34,000) T/variant-allele of rs28371725 (CYP2D*41) was associated with increased fall risk (OR = 1.06, 95% CI 1.01–1.12). G/non-variant-allele of rs4244285 (CY2C19*2) was associated with decrease

Published
2022

198. An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels

Author

de Leon, Jose, Schoretsanitis, Georgios, Smith, Robert L., Molden, Espen, Solismaa, Anssi, Seppala, Niko, Kopecek, Miloslav, Svancer, Patrik, Olmos, Ismael, Ricciardi, Carina, Iglesias-Garcia, Celso, Iglesias-Alonso, Ana, Spina, Edoardo, Ruan, Can-Jun, Wang, Chuan-Yue, Wang, Gang, Tang, Yi-Lang, Lin, Shih-Ku, Lane, Hsien-Yuan, Kim, Yong Sik, Kim, Se Hyun, Rajkumar, Anto P., Gonzalez-Esquivel, Dinora F., Jung-Cook, Helgi, Baptista, Trino, Rohde, Christopher, Nielsen, Jimmi, Verdoux, Helene, Quiles, Clelia, Sanz, Emilio J., De las Cuevas, Carlos, Cohen, Dan, Schulte, Peter F. J., Ertugrul, Aygun, Chopra, Nitin, McCollum, Betsy, Shelton, Charles, Cotes, Robert O., Kaithi, Arun R., Kane, John M., Farooq, Saeed, Ng, Chee H., Bilbily, John, Hiemke, Christoph, Lopez-Jaramillo, Carlos, McGrane, Ian, Lana, Fernando, Eap, Chin B., Arrojo-Romero, Manuel, Seifritz, Erich, Every-Palmer, Susanna, Bousman, Chad A., Bebawi, Emmanuel, Bhattacharya, Rahul, Kelly, Deanna L., Otsuka, Yuji, Lazary, Judit, Torres, Rafael, Yecora, Agustin, Motuca, Mariano, Chan, Sherry K. W., Zolezzi, Monica, Ouanes, Sami, De Berardis, Domenico, Grover, Sandeep, Procyshyn, Ric M., Adebayo, Richard A., Kirilochev, Oleg O., Soloviev, Andrey, Fountoulakis, Konstantinos N., Wilkowska, Alina, Ayub, Muhammad, Silva, Alzira, Bonelli, Raphael M., Villagran-Moreno, Jose M., Crespo-Facorro, Benedicto, Temmingh, Henk, Decloedt, Eric, Pedro, Maria R., Takeuchi, Hiroyoshi, Tsukahara, Masaru, Gruender, Gerhard, Sagud, Marina, Celofiga, Andreja, Ristic, Dragana Ignjatovic, Ortiz, Bruno B., Elkis, Helio, Palha, Antonio J. Pacheco, LLerena, Adrian, Fernandez-Egea, Emilio, Siskind, Dan, Weizman, Abraham, Masmoudi, Rim, Saffian, Shamin Mohd, Leung, Jonathan G., Buckley, Peter F., Marder, Stephen R., Citrome, Leslie, Freudenreich, Oliver, Correll, Christoph U., Muller, Daniel J., Anil Yagcioglu, A. Elif, Radulescu, Flavian S., Cubala, Wieslaw J., de Leon, Jose, Schoretsanitis, Georgios, Smith, Robert L., Molden, Espen, Solismaa, Anssi, Seppala, Niko, Kopecek, Miloslav, Svancer, Patrik, Olmos, Ismael, Ricciardi, Carina, Iglesias-Garcia, Celso, Iglesias-Alonso, Ana, Spina, Edoardo, Ruan, Can-Jun, Wang, Chuan-Yue, Wang, Gang, Tang, Yi-Lang, Lin, Shih-Ku, Lane, Hsien-Yuan, Kim, Yong Sik, Kim, Se Hyun, Rajkumar, Anto P., Gonzalez-Esquivel, Dinora F., Jung-Cook, Helgi, Baptista, Trino, Rohde, Christopher, Nielsen, Jimmi, Verdoux, Helene, Quiles, Clelia, Sanz, Emilio J., De las Cuevas, Carlos, Cohen, Dan, Schulte, Peter F. J., Ertugrul, Aygun, Chopra, Nitin, McCollum, Betsy, Shelton, Charles, Cotes, Robert O., Kaithi, Arun R., Kane, John M., Farooq, Saeed, Ng, Chee H., Bilbily, John, Hiemke, Christoph, Lopez-Jaramillo, Carlos, McGrane, Ian, Lana, Fernando, Eap, Chin B., Arrojo-Romero, Manuel, Seifritz, Erich, Every-Palmer, Susanna, Bousman, Chad A., Bebawi, Emmanuel, Bhattacharya, Rahul, Kelly, Deanna L., Otsuka, Yuji, Lazary, Judit, Torres, Rafael, Yecora, Agustin, Motuca, Mariano, Chan, Sherry K. W., Zolezzi, Monica, Ouanes, Sami, De Berardis, Domenico, Grover, Sandeep, Procyshyn, Ric M., Adebayo, Richard A., Kirilochev, Oleg O., Soloviev, Andrey, Fountoulakis, Konstantinos N., Wilkowska, Alina, Ayub, Muhammad, Silva, Alzira, Bonelli, Raphael M., Villagran-Moreno, Jose M., Crespo-Facorro, Benedicto, Temmingh, Henk, Decloedt, Eric, Pedro, Maria R., Takeuchi, Hiroyoshi, Tsukahara, Masaru, Gruender, Gerhard, Sagud, Marina, Celofiga, Andreja, Ristic, Dragana Ignjatovic, Ortiz, Bruno B., Elkis, Helio, Palha, Antonio J. Pacheco, LLerena, Adrian, Fernandez-Egea, Emilio, Siskind, Dan, Weizman, Abraham, Masmoudi, Rim, Saffian, Shamin Mohd, Leung, Jonathan G., Buckley, Peter F., Marder, Stephen R., Citrome, Leslie, Freudenreich, Oliver, Correll, Christoph U., Muller, Daniel J., Anil Yagcioglu, A. Elif, Radulescu, Flavian S., and Cubala, Wieslaw J.

Abstract

This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas' original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300-600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75-150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175-300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100-200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250-400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150-300 mg/day, and 6) in the US with ancestries other than from Asia or the original people fr

Published
2022

199. Development of the ADFICE_IT Models for Predicting Falls and Recurrent Falls in Community-Dwelling Older Adults:Pooled Analyses of European Cohorts With Special Attention to Medication

Author

Van De Loo, Bob, Seppala, Lotta J., Van Der Velde, Nathalie, Medlock, Stephanie, Denkinger, Michael, De Groot, Lisette C.P.G.M., Kenny, Rose Anne, Moriarty, Frank, Rothenbacher, Dietrich, Stricker, Bruno, Uitterlinden, André, Abu-Hanna, Ameen, Heymans, Martijn W., Van Schoor, Natasja, Van De Loo, Bob, Seppala, Lotta J., Van Der Velde, Nathalie, Medlock, Stephanie, Denkinger, Michael, De Groot, Lisette C.P.G.M., Kenny, Rose Anne, Moriarty, Frank, Rothenbacher, Dietrich, Stricker, Bruno, Uitterlinden, André, Abu-Hanna, Ameen, Heymans, Martijn W., and Van Schoor, Natasja

Abstract

Background: Use of fall prevention strategies requires detection of high-risk patients. Our goal was to develop prediction models for falls and recurrent falls in community-dwelling older adults and to improve upon previous models by using a large, pooled sample and by considering a wide range of candidate predictors, including medications. Methods: Harmonized data from 2 Dutch (LASA, B-PROOF) and 1 German cohort (ActiFE Ulm) of adults aged ≥65 years were used to fit 2 logistic regression models: one for predicting any fall and another for predicting recurrent falls over 1 year. Model generalizability was assessed using internal-external cross-validation. Results: Data of 5 722 participants were included in the analyses, of whom 1 868 (34.7%) endured at least 1 fall and 702 (13.8%) endured a recurrent fall. Positive predictors for any fall were: educational status, depression, verbal fluency, functional limitations, falls history, and use of antiepileptics and drugs for urinary frequency and incontinence; negative predictors were: body mass index (BMI), grip strength, systolic blood pressure, and smoking. Positive predictors for recurrent falls were: educational status, visual impairment, functional limitations, urinary incontinence, falls history, and use of anti-Parkinson drugs, antihistamines, and drugs for urinary frequency and incontinence; BMI was a negative predictor. The average C-statistic value was 0.65 for the model for any fall and 0.70 for the model for recurrent falls. Conclusion: Compared with previous models, the model for recurrent falls performed favorably while the model for any fall performed similarly. Validation and optimization of the models in other populations are warranted.

Published
2022

200. Development of the ADFICE_IT Models for Predicting Falls and Recurrent Falls in Community-Dwelling Older Adults : Pooled Analyses of European Cohorts With Special Attention to Medication

Author

Van De Loo, Bob, Seppala, Lotta J., Van Der Velde, Nathalie, Medlock, Stephanie, Denkinger, Michael, De Groot, Lisette C.P.G.M., Kenny, Rose Anne, Moriarty, Frank, Rothenbacher, Dietrich, Stricker, Bruno, Uitterlinden, André, Abu-Hanna, Ameen, Heymans, Martijn W., Van Schoor, Natasja, Van De Loo, Bob, Seppala, Lotta J., Van Der Velde, Nathalie, Medlock, Stephanie, Denkinger, Michael, De Groot, Lisette C.P.G.M., Kenny, Rose Anne, Moriarty, Frank, Rothenbacher, Dietrich, Stricker, Bruno, Uitterlinden, André, Abu-Hanna, Ameen, Heymans, Martijn W., and Van Schoor, Natasja

Abstract

Background: Use of fall prevention strategies requires detection of high-risk patients. Our goal was to develop prediction models for falls and recurrent falls in community-dwelling older adults and to improve upon previous models by using a large, pooled sample and by considering a wide range of candidate predictors, including medications. Methods: Harmonized data from 2 Dutch (LASA, B-PROOF) and 1 German cohort (ActiFE Ulm) of adults aged ≥65 years were used to fit 2 logistic regression models: one for predicting any fall and another for predicting recurrent falls over 1 year. Model generalizability was assessed using internal-external cross-validation. Results: Data of 5 722 participants were included in the analyses, of whom 1 868 (34.7%) endured at least 1 fall and 702 (13.8%) endured a recurrent fall. Positive predictors for any fall were: educational status, depression, verbal fluency, functional limitations, falls history, and use of antiepileptics and drugs for urinary frequency and incontinence; negative predictors were: body mass index (BMI), grip strength, systolic blood pressure, and smoking. Positive predictors for recurrent falls were: educational status, visual impairment, functional limitations, urinary incontinence, falls history, and use of anti-Parkinson drugs, antihistamines, and drugs for urinary frequency and incontinence; BMI was a negative predictor. The average C-statistic value was 0.65 for the model for any fall and 0.70 for the model for recurrent falls. Conclusion: Compared with previous models, the model for recurrent falls performed favorably while the model for any fall performed similarly. Validation and optimization of the models in other populations are warranted.

Published
2022

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