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المؤلفون: Sandborn, Wj, Feagan, Bg, Rutgeerts, P, Hanauer, S, Colombel, Jf, Sands, Be, Lukas, M, Fedorak, Rn, Lee, S, Bressler, B, Fox, I, Rosario, M, Sankoh, S, Xu, J, Stephens, K, Milch, C, Parikh, A, Bampton P, GEMINI 2 Study G. r. o. u. p., Borody, T, Chung, A, Debinski, H, Florin, T, Hetzel, D, Jakobovits, S, Lawrance, I, Leong, R, Macrae, F, Mitchell, B, Moore, G, Pavli, P, Samuel, D, Weltman, M, Haas, T, Reinisch, W, Vogel, W, Baert, F, De Maeyer, M, De Vos, M, Dewit, O, D'Haens, G, Louis, E, Muls, V, Van Assche, G, Krastev, Z, Nikolovska, D, Petrov, P, Petrov, A, Stoinov, S, Tchernev, K, Vasileva, G, Aumais, G, Axler, J, Bailey, R, Bernstein, C, Bitton, A, Bourdages, R, Cohen, A, Devroede, G, Dhalla, S, Feagan, B, Fedorak, R, Green, D, Greenberg, G, Jones, J, Larkai, E, Macintosh, D, Panaccione, R, Ponich, T, Singh, R, Sy, R, Wiesinger, H, Albin, A, Douda, L, Horny, I, Stehlik, J, Stuksa, J, Volfova, M, Vyhnalek, P, Zadorova, Z, Andersen, V, Bendtsen, F, Fallingborg, J, Rannem, T, Maelt, A, Margus, B, Salupere, R, Allez, M, Des Varennes SB, Desreumaux, P, Dupas, Jl, Grimaud, Jc, Hebuterne, X, Lerebours, E, Picon, L, Zerbib, F, Aldinger, V, Baumgart, D, Buening, C, Dollinger, M, Hoffmann, P, Howaldt, S, Klaus, J, Konturek, Jw, Krummenerl, T, Malfertheiner, P, Schmidt, W, Schreiber, S, Seidler, U, Stallmach, A, Stremmel, W, Zeitz, M, Mantzaris, G, Triantafyllou, K, Ng, C, Bene, L, Fazekas, I, Fejes, R, Gall, J, Horvat, G, Hunyady, B, Salamon, A, Toth, T, Tulassay, Z, Varga, E, Varga, M, Varga Szabo, L, Vincze, A, Oddsson, E, Örvar, K, Ahuja, V, Amarapurkar, D, Chandra, A, Koshy, A, Krishna, P, Ramakrishna, K, Reddy, N, Thorat, V, Patchett, S, Ryan, B, Ben Horin, S, Fishman, S, Lavy, A, Rachmilewitz, D, Ardizzone, S, Corazziari, E, Danese, S, Fries, Walter, Gasbarrini, A, Kohn, A, Sturniolo, Gc, Danilans, A, George, Am, Hilmi, In, Engels, Lg, Ponsioen, Cy, van der Woude CJ, Gearry, R, Haines, M, Schultz, M, Wallace, I, Wyeth, J, Florholmen, J, Jahnsen, J, Lygren, I, Röseth, A, Ciecko Michalska, I, Gonciarz, M, Horynski, M, Huk, J, Jamrozik Kruk, Z, Janke, A, Klupinska, G, Marecik, J, Paradowski, L, Rudzinski, J, Rydzewska, G, Han, Ds, Hong, Sp, Kim, Hj, Kim, Js, Kim, Ko, Kim, Yh, Yang, Sk, Gheorghe, Ls, Voiosu, Rm, Alexeeva, O, Baranovsky, A, Bunkova, E, Burnevich, E, Dolgikh, O, Grinevich, V, Lakhin, A, Tarabar, D, Ling, Kl, Bunganic, I, Cernok, S, Gregus, M, Coetzer, T, Grundling, H, Moola, Sa, Wright, Jp, Ziady, C, Bermejo, F, Calvet, X, Herrerias, Jm, Perez Calle JL, Perez Gisbert, J, Hertervig, E, Karlen, P, Michetti, P, Rogler, G, Seibold, F, Wu, Dc, Atug, O, Kurdas, Oo, Datsenko, O, Dorofyeyev, A, Dudar, L, Golovchenko, O, Klyarits'Ka, I, Skrypnyk, I, Hawthorne, Ab, Middleton, S, Abreu, M, Bala, N, Becker, S, Behm, B, Braun, R, Bukhari, M, Chen, S, Coates, A, Dar, S, Dassopoulos, T, De Villiers, W, Desautels, S, Desta, T, Dimitroff, J, Dryden, G, Duvall, A, Farraye, F, Fein, S, Liu, Bf, Gatof, D, Geenen, D, Ginsburg, P, Glombicki, A, Glover, S, Gordon, G, Grisolano, S, Hanson, J, Hardi, R, Hoffman, B, Isaacs, K, Kim, C, Koval, G, Lashner, B, Lawitz, E, Leman, B, Levine, J, Loftus, E, Mahadevan, U, Mannon, P, Marcet, J, Matsuyama, R, Matusow, G, Mccabe, R, Mirkin, K, Murphy, M, Mushahwar, A, Mutlu, E, Nagrani, M, Nguyen, D, Nichols, M, Nieves Ramirez, A, Oubre, B, Pace, S, Pandak, W, Perera, L, Quadri, A, Quallich, L, Rajapakse, R, Randall, C, Regueiro, M, Safdi, A, Sandborn, W, Sands, B, Saubermann, L, Scherl, E, Schwartz, D, Sedghi, S, Shafran, I, Shepard, R, Siegel, C, Stein, L, Tatum, H, Triebling, A, Vasudeva, R, Winston, B, Wolf, D, Younes, Z, Jewell, D, Mahon, J, Rothstein, R, Snydman, D, Massaro, J, Clifford, D, Berger, J, Major, E, Provenzale, J, Lev, M.
المساهمون: GEMINI 2 Study Group, Bampton, P., Borody, T., Chung, A., Debinski, H., Florin, T., Hetzel, D., Jakobovits, S., Lawrance, I., Leong, R., Macrae, F., Mitchell, B., Moore, G., Pavli, P., Samuel, D., Weltman, M., Haas, T., Reinisch, W., Vogel, W., Baert, F., De Maeyer, M., De Vos, M., Dewit, O., D'Haens, G., Louis, E., Muls, V., Van Assche, G., Krastev, Z., Nikolovska, D., Petrov, P., Petrov, A., Stoinov, S., Tchernev, K., Vasileva, G., Aumais, G., Axler, J., Bailey, R., Bernstein, C., Bitton, A., Bourdages, R., Bressler, B., Cohen, A., Devroede, G., Dhalla, S., Feagan, B., Fedorak, R., Green, D., Greenberg, G., Jones, J., Larkai, E., MacIntosh, D., Panaccione, R., Ponich, T., Singh, R., Sy, R., Wiesinger, H., Albin, A., Douda, L., Horny, I., Lukas, M., Stehlik, J., Stuksa, J., Volfova, M., Vyhnalek, P., Zadorova, Z., Andersen, V., Bendtsen, F., Fallingborg, J., Rannem, T., Maelt, A., Margus, B., Salupere, R., Allez, M., Des Varennes SB., Desreumaux, P., Dupas, JL., Grimaud, JC., Hebuterne, X., Lerebours, E., Picon, L., Zerbib, F., Aldinger, V., Baumgart, D., Buening, C., Dollinger, M., Hoffmann, P., Howaldt, S., Klaus, J., Konturek, JW., Krummenerl, T., Malfertheiner, P., Schmidt, W., Schreiber, S., Seidler, U., Stallmach, A., Stremmel, W., Zeitz, M., Mantzaris, G., Triantafyllou, K., Ng, C., Bene, L., Fazekas, I., Fejes, R., Gall, J., Horvat, G., Hunyady, B., Salamon, A., Toth, T., Tulassay, Z., Varga, E., Varga, M., Varga-Szabo, L., Vincze, A., Oddsson, E., Örvar, K., Ahuja, V., Amarapurkar, D., Chandra, A., Koshy, A., Krishna, P., Ramakrishna, K., Reddy, N., Thorat, V., Patchett, S., Ryan, B., Ben Horin, S., Fishman, S., Lavy, A., Rachmilewitz, D., Ardizzone, S., Corazziari, E., Danese, S., Fries, W., Gasbarrini, A., Kohn, A., Sturniolo, GC., Danilans, A., George, AM., Hilmi, IN., Engels, LG., Ponsioen, CY., van der Woude CJ., Gearry, R., Haines, M., Schultz, M., Wallace, I., Wyeth, J., Florholmen, J., Jahnsen, J., Lygren, I., Röseth, A., Ciecko-Michalska, I., Gonciarz, M., Horynski, M., Huk, J., Jamrozik-Kruk, Z., Janke, A., Klupinska, G., Marecik, J., Paradowski, L., Rudzinski, J., Rydzewska, G., Han, DS., Hong, SP., Kim, HJ., Kim, JS., Kim, KO., Kim, YH., Yang, SK., Gheorghe, LS., Voiosu, RM., Alexeeva, O., Baranovsky, A., Bunkova, E., Burnevich, E., Dolgikh, O., Grinevich, V., Lakhin, A., Tarabar, D., Ling, KL., Bunganic, I., Cernok, S., Gregus, M., Coetzer, T., Grundling, H., Moola, SA., Wright, JP., Ziady, C., Bermejo, F., Calvet, X., Herrerias, JM., Perez Calle JL., Perez Gisbert, J., Hertervig, E., Karlen, P., Michetti, P., Rogler, G., Seibold, F., Wu, DC., Atug, O., Kurdas, OO., Datsenko, O., Dorofyeyev, A., Dudar, L., Golovchenko, O., Klyarits'ka, I., Skrypnyk, I., Hawthorne, AB., Middleton, S., Abreu, M., Bala, N., Becker, S., Behm, B., Braun, R., Bukhari, M., Chen, S., Coates, A., Dar, S., Dassopoulos, T., De Villiers, W., Desautels, S., Desta, T., Dimitroff, J., Dryden, G., Duvall, A., Farraye, F., Fein, S., Liu, BF., Gatof, D., Geenen, D., Ginsburg, P., Glombicki, A., Glover, S., Gordon, G., Grisolano, S., Hanauer, S., Hanson, J., Hardi, R., Hoffman, B., Isaacs, K., Kim, C., Koval, G., Lashner, B., Lawitz, E., Lee, S., Leman, B., Levine, J., Loftus, E., Mahadevan, U., Mannon, P., Marcet, J., Matsuyama, R., Matusow, G., McCabe, R., Mirkin, K., Murphy, M., Mushahwar, A., Mutlu, E., Nagrani, M., Nguyen, D., Nichols, M., Nieves Ramirez, A., Oubre, B., Pace, S., Pandak, W., Perera, L., Quadri, A., Quallich, L., Rajapakse, R., Randall, C., Regueiro, M., Safdi, A., Sandborn, W., Sands, B., Saubermann, L., Scherl, E., Schwartz, D., Sedghi, S., Shafran, I., Shepard, R., Siegel, C., Stein, L., Tatum, H., Triebling, A., Vasudeva, R., Winston, B., Wolf, D., Younes, Z., Feagan, BG., Colombel, JF., Rutgeerts, P., Sandborn, WJ., Sands, BE., Jewell, D., Mahon, J., Rothstein, R., Snydman, D., Massaro, J., Clifford, D., Berger, J., Major, E., Provenzale, J., Lev, M., Medical Microbiology & Infectious Diseases
المصدر: Sandborn, W J, Feagan, B G, Rutgeerts, P, Hanauer, S, Colombel, J-F, Sands, B E, Lukas, M, Fedorak, R N, Lee, S, Bressler, B, Fox, I, Rosario, M, Sankoh, S, Xu, J, Stephens, K, Milch, C, Parikh, A, GEMINI 2 Study Group & Andersen, V 2013, ' Vedolizumab as induction and maintenance therapy for Crohn's disease ', The New England Journal of Medicine, vol. 369, no. 8, pp. 711-721 . https://doi.org/10.1056/NEJMoa1215739
New England Journal of Medicine, vol. 369, no. 8, pp. 711-721
New England Journal of Medicine, 369(8), 711-721. Massachussetts Medical Societyمصطلحات موضوعية: Adult, Male, Integrins, medicine.medical_specialty, HUMAN POLYOMAVIRUSES, JC, Antibodies/blood, Antibodies, Monoclonal, Humanized/adverse effects, Antibodies, Monoclonal, Humanized/immunology, Crohn Disease/drug therapy, Double-Blind Method, Drug Administration Schedule, Drug Therapy, Combination, Female, Glucocorticoids/therapeutic use, Humans, Immunosuppressive Agents/therapeutic use, Induction Chemotherapy, Infusions, Intravenous/adverse effects, Integrins/antagonists & inhibitors, Integrins/immunology, Maintenance Chemotherapy, Middle Aged, PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY, Antibodies, Monoclonal, Humanized, Placebo, Gastroenterology, Inflammatory bowel disease, Antibodies, Vedolizumab, CERTOLIZUMAB PEGOL, Natalizumab, Crohn Disease, Maintenance therapy, HUMANIZED ANTIBODY, Internal medicine, Ustekinumab, medicine, Certolizumab pegol, Infusions, Intravenous, Glucocorticoids, NATALIZUMAB, business.industry, Induction chemotherapy, General Medicine, medicine.disease, PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY, RELAPSING MULTIPLE-SCLEROSIS, INFLAMMATORY-BOWEL-DISEASE, HUMAN POLYOMAVIRUSES, HUMANIZED ANTIBODY, CERTOLIZUMAB PEGOL, ULCERATIVE-COLITIS, RANDOMIZED-TRIAL, NATALIZUMAB, JC, RANDOMIZED-TRIAL, digestive system diseases, Surgery, ULCERATIVE-COLITIS, RELAPSING MULTIPLE-SCLEROSIS, business, Immunosuppressive Agents, INFLAMMATORY-BOWEL-DISEASE, medicine.drug
الوصف: BACKGROUND: The efficacy of vedolizumab, an α4β7 integrin antibody, in Crohn's disease is unknown. METHODS: In an integrated study with separate induction and maintenance trials, we assessed intravenous vedolizumab therapy (300 mg) in adults with active Crohn's disease. In the induction trial, 368 patients were randomly assigned to receive vedolizumab or placebo at weeks 0 and 2 (cohort 1), and 747 patients received open-label vedolizumab at weeks 0 and 2 (cohort 2); disease status was assessed at week 6. In the maintenance trial, 461 patients who had had a response to vedolizumab were randomly assigned to receive placebo or vedolizumab every 8 or 4 weeks until week 52. RESULTS: At week 6, a total of 14.5% of the patients in cohort 1 who received vedolizumab and 6.8% who received placebo were in clinical remission (i.e., had a score on the Crohn's Disease Activity Index [CDAI] of ≤150, with scores ranging from 0 to approximately 600 and higher scores indicating greater disease activity) (P=0.02); a total of 31.4% and 25.7% of the patients, respectively, had a CDAI-100 response (≥100-point decrease in the CDAI score) (P=0.23). Among patients in cohorts 1 and 2 who had a response to induction therapy, 39.0% and 36.4% of those assigned to vedolizumab every 8 weeks and every 4 weeks, respectively, were in clinical remission at week 52, as compared with 21.6% assigned to placebo (P
وصف الملف: application/pdf
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المؤلفون: Feagan, Bg, Rutgeerts, P, Sands, Be, Hanauer, S, Colombel, Jf, Sandborn, Wj, Van Assche, G, Axler, J, Kim, Hj, Danese, S, Fox, I, Milch, C, Sankoh, S, Wyant, T, Xu, J, Parikh, A, Bampton P, GEMINI 1 Study G. r. o. u. p., Chung, A, Debinski, H, Florin, T, Hetzel, D, Kronborg, I, Lawrance, I, Leong, R, Macrae, F, Moore, G, Pavli, P, Radford Smith, G, Weltman, M, Haas, T, Reinisch, W, Stockenhuber, F, Vogel, W, De Maeyer, M, De Vos, M, D'Haens, G, Louis, E, Muls, V, Petrov, P, Aumais, G, Bitton, A, Bourdages, R, Bressler, B, Cohen, A, Fedorak, R, Greenberg, G, Jones, J, Kutcher, W, Macintosh, D, Ponich, T, Singh, R, Steinhart, H, Sy, R, Douda, L, Lukas, M, Samek, M, Vyhnalek, P, Woznica, V, Zadorova, Z, Andersen, V, Rannem, T, Staun, M, Maelt, A, Margus, B, Bonaz, B, Coffin, B, Desreumaux, P, Laharie, D, Reimund, Jm, Karaus, M, Pace, A, Ross, M, Schmidt, W, Witthoeft, T, Zeitz, M, Karamanolis, D, Mantzaris, G, Maris, T, Ng, C, Gall, J, Hunyady, B, Szepes, A, Toth, T, Vincze, A, Oddsson, E, Jósefsspktali, Kö, Ahuja, V, Amarapurkar, D, Goenka, M, Habeeb, Ma, Jalihal, U, Kalambe, B, Koshy, A, Kumar, R, Prasad, V, Reddy, N, Sekar, T, Shankar, R, Tantry, V, Ryan, B, Avni, Y, Ben Horin, S, Ardizzone, S, Armuzzi, A, Corazziari, E, Fries, Walter, Kohn, A, Lisova, D, George, Am, Hilmi, In, Bhaskaran, Sk, Soon, Sy, Engels, L, Ponsioen, C, Wallace, I, Wyeth, J, Florholmen, J, Jahnsen, J, Lygren, I, Röseth, A, Ciecko Michalska, I, Gonciarz, M, Huk, J, Jamrozik Kruk, Z, Kondusz Szklarz, M, Paradowski, L, Wiechowska Kozlowska, A, Han, Ds, Hong, Sp, Kim, Js, Kim, Ko, Kim, Yh, Yang, Sk, Alexeeva, O, Bunkova, E, Burnevich, E, Dolgikh, O, Kasherininova, I, Khovaeva, Y, Lakhin, A, Ling, Kl, Bester, F, Coetzer, T, Grundling Hde, K, Jackson, Ld, Spies, P, Wright, Jp, Ziady, C, Garcia Planella, E, Perez Gisbert, J, Rogler, G, Seibold, F, Kao, Aw, Wu, Dc, Atug, O, Kurdas, Oo, Hawthorne, Ab, Lindsay, J, Abreu, M, Aggarwal, A, Bala, N, Becker, S, Behm, B, Braun, R, Cohn, W, Cross, R, Dar, S, Dassopoulos, T, De Villiers, W, Desta, T, Dryden, G, Duvall, A, Farraye, F, Fein, S, Liu, Bf, Gatof, D, Geenen, D, Ginsburg, P, Glover, S, Gopal, V, Hanson, J, Hardi, R, Isaacs, K, Jain, R, Karyotakis, N, Korzenik, J, Koshy, G, Koval, G, Lawitz, E, Lee, S, Loftus, E, Luther, R, Mahadevan, U, Mannon, P, Matsuyama, R, Mcintosh, A, Melmed, G, Mirkin, K, Nichols, M, Oubre, B, Pandak, W, Quadri, A, Quallich, L, Randall, C, Rausher, D, Regueiro, M, Safdi, A, Sands, B, Scherl, E, Schneier, J, Schwartz, D, Sedghi, S, Shafran, I, Siegel, C, Stein, L, Tatum, H, Weinberg, D, Winston, B, Wolf, D, Younes, Z, Jewell, D, Mahon, J, Rothstein, R, Snydman, D, Massaro, J, Clifford, D, Berger, J, Major, E, Provenzale, J, Abstract, Lev M.
المساهمون: Feagan, Bg, Rutgeerts, P, Sands, Be, Hanauer, S, Colombel, Jf, Sandborn, Wj, Van Assche, G, Axler, J, Kim, Hj, Danese, S, Fox, I, Milch, C, Sankoh, S, Wyant, T, Xu, J, Parikh, A
المصدر: Feagan, B G, Rutgeerts, P, Sands, B E, Hanauer, S, Colombel, J-F, Sandborn, W J, Van Assche, G, Axler, J, Kim, H-J, Danese, S, Fox, I, Milch, C, Sankoh, S, Wyant, T, Xu, J, Parikh, A, GEMINI 1 Study Group & Andersen, V 2013, ' Vedolizumab as induction and maintenance therapy for ulcerative colitis ', The New England Journal of Medicine, vol. 369, no. 8, pp. 699-710 . https://doi.org/10.1056/NEJMoa1215734
مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Integrins, Placebo, Antibodies, Monoclonal, Humanized, Drug Administration Schedule, law.invention, Vedolizumab, Maintenance Chemotherapy, Maintenance therapy, Randomized controlled trial, Double-Blind Method, law, Internal medicine, medicine, Humans, Glucocorticoids, Aged, business.industry, General Medicine, Induction Chemotherapy, Middle Aged, medicine.disease, Ulcerative colitis, Infliximab, Surgery, Clinical trial, Cohort, Colitis, Ulcerative, Drug Therapy, Combination, Female, business, Immunosuppressive Agents, medicine.drug
الوصف: Gut-selective blockade of lymphocyte trafficking by vedolizumab may constitute effective treatment for ulcerative colitis.We conducted two integrated randomized, double-blind, placebo-controlled trials of vedolizumab in patients with active disease. In the trial of induction therapy, 374 patients (cohort 1) received vedolizumab (at a dose of 300 mg) or placebo intravenously at weeks 0 and 2, and 521 patients (cohort 2) received open-label vedolizumab at weeks 0 and 2, with disease evaluation at week 6. In the trial of maintenance therapy, patients in either cohort who had a response to vedolizumab at week 6 were randomly assigned to continue receiving vedolizumab every 8 or 4 weeks or to switch to placebo for up to 52 weeks. A response was defined as a reduction in the Mayo Clinic score (range, 0 to 12, with higher scores indicating more active disease) of at least 3 points and a decrease of at least 30% from baseline, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1.Response rates at week 6 were 47.1% and 25.5% among patients in the vedolizumab group and placebo group, respectively (difference with adjustment for stratification factors, 21.7 percentage points; 95% confidence interval [CI], 11.6 to 31.7; P0.001). At week 52, 41.8% of patients who continued to receive vedolizumab every 8 weeks and 44.8% of patients who continued to receive vedolizumab every 4 weeks were in clinical remission (Mayo Clinic score ≤2 and no subscore1), as compared with 15.9% of patients who switched to placebo (adjusted difference, 26.1 percentage points for vedolizumab every 8 weeks vs. placebo [95% CI, 14.9 to 37.2; P0.001] and 29.1 percentage points for vedolizumab every 4 weeks vs. placebo [95% CI, 17.9 to 40.4; P0.001]). The frequency of adverse events was similar in the vedolizumab and placebo groups.Vedolizumab was more effective than placebo as induction and maintenance therapy for ulcerative colitis. (Funded by Millennium Pharmaceuticals; GEMINI 1 ClinicalTrials.gov number, NCT00783718.).
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المؤلفون: Worsfold O, Wright Jp, Himmelhaus M
المصدر: Journal of nanoscience and nanotechnology. 8(11)
مصطلحات موضوعية: Materials science, Silicon, Scanning electron microscope, Macromolecular Substances, Surface Properties, Biomedical Engineering, Molecular Conformation, chemistry.chemical_element, Bioengineering, Substrate (electronics), Materials Testing, Nanotechnology, General Materials Science, Particle Size, Field emission gun, business.industry, General Chemistry, Condensed Matter Physics, Evaporation (deposition), Chamber pressure, Nanostructures, chemistry, Optoelectronics, Nanosphere lithography, Gases, Gold, business, Ternary operation, Crystallization
الوصف: By combining nanosphere lithography (NSL) with metal evaporation at two different chamber pressures, ternary metallic nanostructures with 3D topography were fabricated and characterized by field emission gun scanning electron microscopy (FEG-SEM) and atomic force microscopy (AFM). The nanostructures consist of 340 nm silicon patches surrounded by a chromium mesh of varying height and gold triangular pillars with a height of 40 nm and a diameter of about 200 nm. While NSL was applied due to its ease of use, evaporation at different chamber pressures can be combined with any kind of template mask comprising convex shape to yield novel kinds of ternary nanostructures analogous to the ones presented here. The method shows to be more versatile than plasma-based deposition techniques due to avoidance of substrate charging effects and a freely adjustable chamber pressure.
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0aedabc25f041d7c7e7ad7e797614c45
https://pubmed.ncbi.nlm.nih.gov/19198323