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1
van Dusseldorp, Michael, und Michael Corbey. „‘Eerlijk zullen we alles delen…’“. Maandblad Voor Accountancy en Bedrijfseconomie 92, Nr. 9/10 (02.11.2018): 243–54. http://dx.doi.org/10.5117/mab.92.28604.
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Binnen de medisch specialistische bedrijven (MSB’s) in de Nederlandse ziekenhuizen wordt voor de winstverdeling sinds 2015 op grote schaal gebruik gemaakt van een winstverdelingssysteem dat is geënt op benchmarking en dat is ontwikkeld door het adviesbureau LOGEX. Het winstverdelingssysteem wordt dan ook het LOGEX Prestatiemodel genoemd. Dit artikel onderzoekt de vraag hoe dit prestatiemodel door de praktijk wordt gewaardeerd en of verbeteringen mogelijk zijn. De inrichting, de voor- en nadelen, knelpunten, en de ontwikkelingsmogelijkheden zijn onderzocht door middel van een zelf ontwikkelde en gevalideerde online-vragenlijst. Deze vragenlijst is uitgezet onder alle financieel managers van de MSB’s in de topklinische ziekenhuizen (STZ-ziekenhuizen) in Nederland. Hoewel in de inrichting van het Prestatiemodel en de winstverdeling binnen MSB’s verschillende keuzes zijn gemaakt, en ook diverse knelpunten worden gesignaleerd, is het eindoordeel over het LOGEX Prestatiemodel unaniem positief. Ontwikkelingsmogelijkheden zijn er op het gebied van productiebegroting, kwaliteitsmeting, wegingsproblemen, disutility, en kostenverdeling.
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Fouvry, Etienne, und M. Ram Murty. „On the Distribution of Supersingular Primes“. Canadian Journal of Mathematics 48, Nr. 1 (01.02.1996): 81–104. http://dx.doi.org/10.4153/cjm-1996-004-7.
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AbstractLet E be a fixed elliptic curve defined over the rational numbers. We prove that the number of primes p ≤ x such that E has supersingular reduction mod p is greater than for any positive δ and x sufficiently large. Here logkx is defined recursively as log(logk-1 x) and log1x = logx. We also establish several results related to the Lang-Trotter conjecture.
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Lodder, Josje, Bastiaan Heeren und Johan Jeuring. „A comparison of elaborated and restricted feedback in LogEx, a tool for teaching rewriting logical formulae“. Journal of Computer Assisted Learning 35, Nr. 5 (21.06.2019): 620–32. http://dx.doi.org/10.1111/jcal.12365.
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Bakkal-Lagarde, Marie-Claude. „Fay-aux-Loges (Loiret). La Loge Cognet“. Archéologie médiévale, Nr. 38 (01.12.2008): 294. http://dx.doi.org/10.4000/archeomed.21296.
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Christodoulou, Garofalo, Echeverri, Pelet und Mouhsine. „Dorsal Hemi-Lithotomy Position for Femoral Fracture Nailing and the Well Leg Compartment Syndrome. Report of Two Cases, Review of the Literature“. Swiss Surgery 8, Nr. 4 (01.08.2002): 193–96. http://dx.doi.org/10.1024/1023-9332.8.4.193.
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Le syndrome de loge sur positionnement prolongé en lithotomie ou en hémilithitomie, est une complication rare en chirurgie. Les dommages neurovasculaires sont souvent permanents. On reporte deux cas d'ostéosynthèse du fémur en position d'hemilithotomie, compliqués d'un syndrome de loge de la jambe controlatérale. Une revue de la littérature sur les 40 cas décrits, jusqu'à ce jour, nous démontre que cette complication est fortement liée au positionnement du patient et à la durée opératoire. Compte tenu du pronostic fonctionnel incertain, une limitation du temps de positionnement en lithotomie doit être recherchée. La surveillance postopératoire doit être rigoureuse et sans hésitation quant à une fasciotomie éventuelle sur simple examen clinique ou après la mesure de la pression dans les loges. Une technique de positionnement sur la table orthopédique est proposée.
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Dimanche, Gérard. „Loges militaires et militaires en loges“. Humanisme N° 288, Nr. 2 (01.05.2010): 63–73. http://dx.doi.org/10.3917/huma.288.0063.
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Clairemidi, A., A. Sauvage, C. Brulard, G. Wavreille und C. Fontaine. „Aponévrotomie endoscopique des loges musculaires de l’avant-bras dans le syndrome de loge chronique d’effort : étude expérimentale cadavérique“. Chirurgie de la Main 30, Nr. 6 (Dezember 2011): 469. http://dx.doi.org/10.1016/j.main.2011.10.135.
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Mollier, Pierre. „Premières loges“. Humanisme N° 276, Nr. 1 (01.03.2007): 99–101. http://dx.doi.org/10.3917/huma.276.0099.
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Wang, Jian Hua, Yun Cheng Wang, Fei Xie und Xu Huang. „Strength Analysis of Logix Gear Based on UG“. Applied Mechanics and Materials 86 (August 2011): 492–95. http://dx.doi.org/10.4028/www.scientific.net/amm.86.492.
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According to the tooth profile theory of Logix gear, this paper discussed a method of parametric modeling based on UG. By this method, 3D model of Logix gear with different parameters can be easily and quickly built, though tooth profile is complicated. And then, it analyzed the bending stress and contact stress of Logix gear. By comparison with the standard involute gear, it showed that Logix gear has higher bending and contact strength. So it is possible this type of gear can be applied in the case of heavy load. So it provided some practical technical guidance on the research of high strength gear and the application of Logix gear.
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Le Moal, René. „Musique maçonnique, en loge ou hors loge“. La chaîne d'union N° 47, Nr. 1 (04.01.2009): 1. http://dx.doi.org/10.3917/cdu.047.0001.
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An, Ai Qin, Ming Hua Pang, Lian Feng Zhang und Yong Fang Nie. „The Studying of Logix Gear Construction Principle and Parameter Simulation Using Matlab“. Applied Mechanics and Materials 80-81 (Juli 2011): 1118–22. http://dx.doi.org/10.4028/www.scientific.net/amm.80-81.1118.
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Logix gear is a new gear based on new tooth profile theory. On the primary, the forming principle of the logix gear tooth profile is analysed. Then the tooth profile curve equations of logix gear are derived, and their center coordinate equations of base circle are given. According these equations, their curves are simulated using Matlab, which are corresponded to practical tests. The study lays a foundation of computer aided design of the logix gears. And the study can be used to perfect mathematical models and to optimize manufacturing methods.
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Letenneur, J., und G. Pietu. „Syndromes des loges“. EMC - Appareil locomoteur 1, Nr. 1 (Januar 2006): 1–13. http://dx.doi.org/10.1016/s0246-0521(05)40321-6.
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Solignac, Matthieu. „Loger les morts“. Regards croisés sur l'économie 9, Nr. 1 (2011): 182. http://dx.doi.org/10.3917/rce.009.0182.
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BONNEVIE, L., R. CLEMENT, P. LARROQUE, D. FONTES, J. GARCIN und X. CHANUDET. „Syndrome des loges“. EMC - Cardiologie-Angéiologie 1, Nr. 4 (November 2004): 413–25. http://dx.doi.org/10.1016/s1762-6137(04)00046-6.
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Bonnevie, L., R. Clément, P. Larroque, D. Fontes, J. M. Garcin und X. Chanudet. „Syndrome des loges“. EMC - Angéiologie 1, Nr. 1 (Januar 2006): 1–9. http://dx.doi.org/10.1016/s1290-0176(04)40118-5.
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Letenneur, J., und G. Pietu. „Syndromes des loges“. EMC - Rhumatologie-Orthopédie 2, Nr. 5 (September 2005): 518–35. http://dx.doi.org/10.1016/j.emcrho.2005.05.001.
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Conte, Charles. „La loge“. Médium 20 - 21, Nr. 3 (2009): 310. http://dx.doi.org/10.3917/mediu.020.0310.
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Inge Carpenter, Lindsay. „LOEX 2018“. Journal of Information Literacy 12, Nr. 1 (04.06.2018): 147. http://dx.doi.org/10.11645/12.1.2480.
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Inge Carpenter, Lindsay. „LOEX 2018“. Journal of Information Literacy 12, Nr. 1 (04.06.2018): 147. http://dx.doi.org/10.11645/jil.v12i1.2480.
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Liu, Hu Ran. „The Analytical Method of the Construction of the Profile of the Basic Rack for Equal Conjugate Curvature“. Applied Mechanics and Materials 44-47 (Dezember 2010): 2897–901. http://dx.doi.org/10.4028/www.scientific.net/amm.44-47.2897.
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After an extensive research on the fundamental theory, the theoretical basis for the Logix gearing will be presented in this paper. This includes the theory for gear meshing with high degree of contact. In comparison to previous studies, the theory of this paper is more restricted going beyond third order parameters into the fourth order, the teeth profile had one order of contact higher than that of the Logix gearing. So that further improved the contact strength of tooth profile. A large category of gearings with high order of contact was presented, while the Logix gear is only one of them, or the special example in realization of my theory. In the Logix gearing, the zigzag curvature center curve of media rank does not always lay about the pitch line and does not extend along the pitch line continuously and steadily. It goes forward and returns. So that, in terms of properties of the transverse engagement, the Logix gearing has not much improvement over the traditional Novikov gearing (in which the transverse engagement is temporally). In my gearing the curvature center of media rank extend along the pitch line continuously and steadily. The transverse engagement factor is larger than that of Logix gearing.
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Terpos, Evangelos, Panagiotis Repousis, Chrysavgi Lalayanni, Evdoxia Hatjiharissi, Theodora Assimakopoulou, Georgios Vassilopoulos, Anastasia Pouli et al. „Pomalidomide Plus Low-Dose Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients: Results of the Real-World “POWERFUL” Study“. Journal of Clinical Medicine 10, Nr. 7 (05.04.2021): 1509. http://dx.doi.org/10.3390/jcm10071509.
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The “POWERFUL” multicenter, retrospective, and prospective study investigated the effectiveness of pomalidomide plus low-dose dexamethasone (POM/LoDex) therapy in relapsed/refractory multiple myeloma in routine care in Greece. Ninety-nine eligible adult patients treated with POM/LoDex according to the approved label after having received ≥2 prior therapies, including lenalidomide and bortezomib, were consecutively enrolled between 16 November 2017 and 21 February 2019 in 18 hematology departments. Fifty patients (50.5%) started POM/LoDex as third-line treatment. During the treatment period (median: 8.3 months; range: 0.3–47.6 months), the median POM dose was 4 mg/day, and 31.3% of the patients received additional antimyeloma agents. The overall response rate was 32.3%. During a median follow-up period of 13.8 months (Kaplan–Meier estimate), the median progression-free survival (PFS) was 10.5 months (95% CI: 7.4–14.4). The PFS was not significantly different between patients receiving POM/LoDex in the third versus later line of therapy, nor between patients receiving concomitant antimyeloma therapy versus POM/LoDEx doublet. During the prospective safety data collection period (median: 7.6 months) among patients with prospective follow-up (N = 75), POM-related adverse event incidence rate was 42.7% (serious: 18.7%; grade ≥ 3 hematological POM-related adverse events: 8.0%). Only neutropenia (13.3%) was reported at a frequency ≥10%. In conclusion, in this real-world study, POM/LoDex displayed a long PFS with no new safety signals emerging.
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Jagannath, Sundar, Craig C. Hofmeister, Rachid C. Baz, David Samuel DiCapua Siegel, Ravi Vij, Christine Chen, Sagar Lonial et al. „Pomalidomide (POM) with or without low-dose dexamethasone (LoDEX) in patients (Pts) with relapsed and refractory multiple myeloma (RRMM): MM-002 phase II age subgroup analysis.“ Journal of Clinical Oncology 31, Nr. 15_suppl (20.05.2013): 8532. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.8532.
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8532 Background: POM demonstrated clinical efficacy and favorable tolerability in RRMM pts previously treated with lenalidomide (LEN) and bortezomib (BORT), in the randomized, multicenter, open label MM-002 phase II trial. This analysis evaluated whether the efficacy and tolerability of POM+LoDEX treatment is consistent across age subgroups. Methods: Pts with RRMM who had received ≥ 2 prior therapies, including LEN and BORT, and were refractory to their last regimen were randomized to either POM+LoDEX (POM 4 mg/day, days 1–21 of a 28-day cycle; LoDEX 40 mg/week) or POM alone. End points included progression-free survival (PFS), response rate (based on EBMT criteria), response duration, and safety. A post-hoc analysis based on age (≤ 65 vs. > 65 yrs) was conducted. Results: A total of 221 pts with a mean age of 64 yrs (range 34–88) were randomized to POM+LoDEX (n = 113) or POM (n = 108). The efficacy outcomes and the most common treatment emergent grade 3/4 adverse events (AEs) for the age subgroups according to treatment arm are presented in the Table. Conclusions: Regardless of age (≤ 65 vs. > 65 yrs), POM with or without LoDEX was effective and generally well tolerated in heavily pretreated RRMM pts who had already received LEN and BORT. POM with or without LoDEX represents a new clinical option for pts previously treated with numerous lines of therapy. Updated data will be presented at the meeting. Clinical trial information: NCT00833833. [Table: see text]
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Stankovic, Vlada. „Tropeoforos kod Mihaila Psela - jedan primer politicke upotrebe retorike“. Zbornik radova Vizantoloskog instituta, Nr. 41 (2004): 133–51. http://dx.doi.org/10.2298/zrvi0441133s.
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(francuski) En raison de sa grande ?rudition, de son talent litt?raire, mais aussi de son caract?re, Michel Psellos est assur?ment un des auteurs byzantins les plus probl?matiques lorsqu'il s'agit de l'interpr?tation et de la compr?hension de ses oeuvres. Le recours ? l'allusion, surtout dans ses ?crits politiques, r?v?le chez un auteur imbu de son savoir le besoin de jouer avec la signification ?officielle?, claire et compr?hensible de tous de ses textes, et une seconde plus profonde en recourant ? des images ?sot?riques, absconses ou difficilement compr?hensibles. Il en est ainsi s'agissant de l'emploi de l'?pith?te tropaiophoros (tropaioph?roz) que Michel Psellos utilise de fa?on sp?cifique, en jouant avec sa signification principale et concr?te. 1. L'emploi du qualificatif tropaiophoros (tropaioph?roz) chez Psellos 1.1. L'?loge ? Constantin Monomaque (Psellus, Orationes, Oratio 2) L'?loge ? Constantin Monomaque r?dig? par Psellos au d?but m?me du r?gne de cet empereur (avril-mai 1043) est caract?ristique lorsqu'il s'agit de l'utilisation du terme tropaiophoros par Psellos. C?l?brant la victoire de l'empereur sur l'usurpateur Georges Maniak?s, Michel Psellos a r?ussi par l'habile emploi de cette ?pith?te ronflante ? qui ? cette ?poque ?tait avant tout utilis?e pour d?signer la fondation de Constantin Monomaque, Saint-Georges Tropaiophoros ? Manganes ? d'exprimer, par le biais de l'ironie, son opinion critique vis-?-vis du nouvel empereur. Proc?dant ? un rappel de l'histoire de Byzance depuis la mort de Jean Tzimisk?s (976) jusqu'? la r?daction de son ?loge, Michel Psellos utilise ? trois reprises l'?pith?te tropaiophoros : 1) associ?e ? Michel IV le Paphlagonien : ...le tropaio- phoros c?leste (immacul?) retourne ? son seigneur, c.-?-d. ? Dieu (ka? tropaioph?roz ana?maktoz pr?z t?n o?ke?on desp?t?n ch?rei ?e??????? x^pei) ; 2) ? Constantin Monomaque : ...et avant le sceptre tu ?tais empereur tropaiophoros (ka? pr? t?n sk?ptr?n basile?z ?stha tropaioph?roz ??o??a????o?) ; 3) et ? l'usurpateur d?fait qui s'?tait dress? contre cet empereur, Georges Maniak?s (symb?llei t? t?z d?se?z strat?g?, nik?, tropaioph?roz ?p?neisi, sobar?teroz t? e?tych?mati g?netai?). Son habile r?partition du terme tropaiophoros dans trois passages ?galement ?loign?s les uns des autres, respectivement dans le premier, deuxi?me et troisi?me tiers de la partie historique de son oratio, met tout particuli?rement en exergue l'importance de ce qualificatif. En tant qu'id?e, la notion de tropaiophoros est sous-jacente ? tout le cours narratif de cet ?loge, constituant d'une certaine fa?on le fondement sur lequel l'orateur a construit et ?labor? son r?cit. Le choix des personnages auxquels Psellos associe l'?pith?te tropaiophoros et les diverses nuances qu'elle rev?t avec chacun d'eux, renforcent l'impression d'un emploi intentionnel d'un terme inhabituel, visant par l? ? transmettre un message politique. Tout d'abord, l'?pith?te tropaiophoros est utilis?e exclusivement pour des personnages contemporains dont le nouvel empereur Constantin Monomaque qu'un lien particulier rattache aux deux autres ? ces deux derniers ayant ?t?, en quelque sorte, l'un comme l'autre ses adversaires, et tous deux l'ayant, du moins provisoirement, d?fait. Autrement dit, seuls les rivaux de Monomaque sont, tout comme lui, qualifi?s de tropaiophoros, alors que ni Basile II, ni Romain Argyre, auquel Psellos dresse des louanges particuli?res dans le cadre de cet ?loge, n'ont re?u cette ?pith?te. Le fait que Michel Psellos ait renonc? par la suite ? utiliser l'?pith?te tropaiophoros dans ses ?loges post?rieurs de Constantin Monomaque et n'ait renou? pleinement avec son emploi qu'apr?s le r?gne de cet empereur, lorsque le temps ?coul? avait ?t? toute actualit? politique ? ce terme, atteste peut-?tre une dose redoubl?e de prudence (voire de crainte?) de la part de cet ?rudit qui redoutait que ne soient d?crypt?es ses allusions et critiques politiques d?guis?es sous formes d'?loges. 1.2. La Chronographie et autres oeuvres de Psellos Le choix m?me des personnages s'?tant vu attribuer l'?pith?te de tropaiophoros dans la Chronographie est d?j? significatif par lui-m?me (Bardas Phocas, Constantin Monomaque, Isaac Comn?ne, Romain Diog?ne et Andronic Doukas, fils du c?sar Jean Doukas), mais Psellos a ?galement exprim? ses positions vis ? vis de ceux-ci ? travers les nuances introduite dans l'emploi de cette ?pith?te avec chacun d'entre eux. Passant de l'ironie non dissimul?e (dans le cas de Romain Diog?ne) ? la moquerie d?guis?e (Andronic Doukas), Psellos joue avec la signification premi?re de l'?pith?te tropaiophoros et ce d'une fa?on qui n'est pas pleinement apparue ? des ?rudits tels que Nic?phore Bryennios et Anne Comn?ne lesquels, proc?dant ? la copie des donn?es fourmes par Psellos, ont repris tel quel ce terme. La possibilit? de l'emploi ambivalent de l'adjectif tropaiophoros nous sont r?v?l?s par Psellos lui-m?me dans sa description de l'empereur H?raclius dans le Logos sur les miracles de l'archange Michel, lorsqu'il dit de cet empereur qu'il ?tait un authentique tropaiophoros (tropaioph?roz ?z ?l?th?z), formule que l'on ne retrouve pour aucun de ses contemporains. 2. Caract?risation de l'emploi du terme tropaiophoros chez Psellos La caract?risation de l'emploi de l'?pith?te tropaiophoros par Psellos, tout en gardant la r?serve qui s'impose, montre que le consul des philosophes a intentionnellement utilis? cette ?pith?te, l'a introduite ? des endroits parfaitement bien choisis et attribu?e ? des personnages bien pr?cis tout en lui conf?rant le plus souvent une connotation ironique. Deux exemples relev?s dans l'?loge de Constantin Monomaque montrent parfaitement que tropaiophoros pouvait ?tre utilis? avec une double signification, ? officielle? (positive) mais aussi ? dissimul?e ? (cachant une critique). L'empereur lui-m?me, alors qu'il n'y va d'aucun m?rite particulier de sa part, et avant m?me de recevoir la couronne imp?riale, est tropaiophoros, qualificatif ? travers lequel Psellos fait, de toute ?vidence, allusion ? l'?rection contemporaine de la fondation du m?me nom de Monomaque, d'une fa?on que l'empereur lui-m?me pouvait comprendre, approuver et r?compenser. Toutefois, l'exemple de Michel IV tir? de ce m?me oratio, montre un autre aspect de l'utilisation de cette ?pith?te ? cet empereur est, en effet, tropaioph?roz ?na?maktoz, ce qui l'?l?ve au-dessus de Monomaque auquel l'?loge est destin?. C'est l? une position conforme ? l'opinion g?n?rale positive de Psellos sur Michel le Paphlagonien que l'on retrouve ?galement exprim?e dans la Chronographie. Dans tous les autres cas ? ? l'exception de celui de l'empereur H?raclius ? une connotation ironique dissimul?e ou un ton moqueur annonce les intentions de l'auteur, en particulier du fait du contraste que Psellos cr?? en attribuant l'?pith?te tropaiophoros ? des empereurs y compris lorqu'il n'y a pas eu de v?ritables victoires. L'?pith?te li?e ? saint Georges, et le plus souvent associ?e dans la rh?torique byzantine ? un empereur ? victorieux a ?t? utilis? par Psellos pour jouer avec sa signification premi?re, mais aussi afin de traduire un message associ? ? son utilisation. 3. Saint Georges Tropaiophoros ? Manganes L'emploi appuy? de l'?pith?te tropaiophoros par Psellos dans son ?loge r?dig? au d?but du r?gne de Constantin Monomaque (avril ? mai 1043) confirme indubitablement que la construction de la fondation de Monomaque ?tait alors commenc?e, 151 mais aussi qu'elle portait d?j? l'?pith?te de tropaiophoros. En outre, le sceau de Skl?raina sur lequel est ?galement mentionn? le sekret?n du saint grand martyr Georges Tropaiophoros, puis l'existence du monast?re du Tropaiophoros avant le mois de mai 1046 (sur la base de la charte de Constantin Monomaque), ainsi que le caract?re et les appellations des ?loges de Mauropous, montrent que l'?glise de Saint-Georges Tropaiophoros a ?t? inaugur?e plus t?t qu'on ne le pensait jusqu'? pr?sent. L'absence de toute description de la nouvelle ?glise, de ses d?corations ou de son luxe dans les r?cits de Jean Mauropous, ce qui ?tait habituel pour les hom?lies qui c?l?braient la sanctification des ?glises depuis l'?poque de patriarche Photius, incite ? conclure qu'il ne s'agissait pas dans ce cas d'un acte aussi solennel. Les imges usuelles et neutres employ?es par Mauropous pour louer les fondations de l'empereur, tel que saint Sion et nouvelle J?rusalem ou la mention stipulant que l'?glise surpassait les autres ?glises par sa taille et ses d?corations, ne doivent en aucun cas ?tre rattach?es avec la c?r?monie de sanctification de l'?glise qui, ? ce qu'il semble, a eu lieu avant mai 1046, et certainement avant le 21 avril 1047 lorsque Jean Mauropous y a prononc? l'?loge de son fondateur, l'empereur Constantin Monomaque.
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Siegel, David Samuel DiCapua, Paul Gerard Guy Richardson, Ravi Vij, Craig C. Hofmeister, Rachid C. Baz, Sundar Jagannath, Christine Chen et al. „Long-term safety and efficacy of pomalidomide (POM) with or without low-dose dexamethasone (LoDEX) in relapsed and refractory multiple myeloma (RRMM) patients enrolled in the MM-002 phase II trial.“ Journal of Clinical Oncology 31, Nr. 15_suppl (20.05.2013): 8588. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.8588.
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8588 Background: MM-002 is a randomized, open-label, multicenter phase II trial evaluating the safety and efficacy of POM with or without LoDEX in advanced RRMM pts. Methods: Pts who had received ≥ 2 prior therapies, including lenalidomide (LEN) and bortezomib (BORT), and were refractory to their last treatment were randomized to POM+LoDEX (POM 4 mg/day, days 1–21 of a 28-day cycle; LoDEX 40 mg/week) or POM alone. End points included progression-free survival (PFS), response rate (according to EBMT criteria and investigator assessment), response duration, overall survival (OS), and safety. The efficacy outcomes are based on the intent-to-treat population (POM+LoDEX, n = 113; POM, n = 108). Results: The median number of prior therapies in each group was 5 (range 1–13). In the POM+LoDEX arm, 30 (27%) pts had high-risk cytogenetics, including del(17p13) and/or t(4p16/14q32). The overall response rate (≥ partial response) was 34% and 15% with POM+LoDEX and POM, respectively, with a median duration of 8.3 (95% CI: 5.8–10.1) and 8.8 (95% CI: 5.5–11.4) mos, respectively. At least minimal response was observed in 45% and 31% of pts, respectively. Median PFS was 4.6 (95% CI: 3.6–5.5) and 2.6 (95% CI: 1.9–2.8) mos with POM+LoDEX and POM, respectively, with a median follow-up of 16.0 and 12.2 mos. Median OS was 16.5 (95% CI: 12.4–18.5) and 13.6 (95% CI: 9.6–18.1) mos, respectively. The most common treatment emergent Gr 3/4 adverse events (AEs) reported in the safety population (n = 219) were neutropenia (44%), anemia (23%), thrombocytopenia (21%), and pneumonia (18%); there were no reports of Gr 3/4 peripheral neuropathy. The incidence of deep-vein thrombosis was low (2%). AEs were managed through dose reductions or interruptions, and supportive care with G-CSF (52%), RBC transfusions (47%), and platelet transfusions (17%). Discontinuations due to AEs were 10%. Conclusions: POM with or without LoDEX is clinically effective and generally well tolerated in RRMM pts who have received multiple prior treatments, including LEN and BORT. AEs were predictable and manageable. Updated data will be presented at the meeting. Clinical trial information: NCT00833833.
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Margetts, Anna. „Transitivity in Saliba-Logea“. Studies in Transitivity 35, Nr. 3 (29.11.2011): 650–75. http://dx.doi.org/10.1075/sl.35.3.06mar.
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Valence and transitivity in Saliba-Logea can be described with reference to three structural levels, the root, the verb and the clause. Phenomena like clauses with both transitive and intransitive features, which are found across the Oceanic language group can be explained through different possible relationships between these levels.
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&NA;. „Lorex suspends alpidem trials“. Inpharma Weekly &NA;, Nr. 844 (Juli 1992): 23. http://dx.doi.org/10.2165/00128413-199208440-00052.
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Pace, Michael L. „From ISLO to LOREX“. Limnology and Oceanography Bulletin 27, Nr. 4 (17.10.2018): 129–30. http://dx.doi.org/10.1002/lob.10268.
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Fidopiastis, Pat M., Sigurd von Boletzky und Edward G. Ruby. „A New Niche for Vibrio logei, the Predominant Light Organ Symbiont of Squids in the GenusSepiola“. Journal of Bacteriology 180, Nr. 1 (01.01.1998): 59–64. http://dx.doi.org/10.1128/jb.180.1.59-64.1998.
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ABSTRACT Two genera of sepiolid squids—Euprymna, found primarily in shallow, coastal waters of Hawaii and the Western Pacific, and Sepiola, the deeper-, colder-water-dwelling Mediterranean and Atlantic squids—are known to recruit luminous bacteria into light organ symbioses. The light organ symbiont ofEuprymna spp. is Vibrio fischeri, but until now, the light organ symbionts of Sepiola spp. have remained inadequately identified. We used a combination of molecular and physiological characteristics to reveal that the light organs ofSepiola affinis and Sepiola robusta contain a mixed population of Vibrio logei and V. fischeri, with V. logei comprising between 63 and 100% of the bacteria in the light organs that we analyzed. V. logei had not previously been known to exist in such symbioses. In addition, this is the first report of two different species of luminous bacteria co-occurring within a single light organ. The luminescence of these symbiotic V. logei strains, as well as that of other isolates of V. logei tested, is reduced when they are grown at temperatures above 20°C, partly due to a limitation in the synthesis of aliphatic aldehyde, a substrate of the luminescence reaction. In contrast, the luminescence of the V. fischeri symbionts is optimal above 24°C and is not enhanced by aldehyde addition. Also, V. fischeri strains were markedly more successful than V. logei at colonizing the light organs of juvenile Euprymna scolopes, especially at 26°C. These findings have important implications for our understanding of the ecological dynamics and evolution of cooperative, and perhaps pathogenic, associations of Vibrio spp. with their animal hosts.
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R, Zill, Dean-Hill H, Alcala M, Snell E und Getz G. „A-113 A Case Study: Utilization of C3 Logix in Serial Evaluation of Concussion in a Multidisciplinary Medical Setting“. Archives of Clinical Neuropsychology 35, Nr. 6 (28.08.2020): 906. http://dx.doi.org/10.1093/arclin/acaa068.113.
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Abstract Objective C3 Logix is a concussion assessment and management system addressing patient care, return to play standards, and rehabilitation or understanding of concussion. This case study demonstrates the utility of the C3 Logix screening measure with a concussion patient in a multidisciplinary medical setting. Repeat C3 Logix screening data was compared to reported symptoms on the Post-Concussion Symptom Scale (PCSS) and interpreted by a physician in medical setting. This case highlights the comparison of C3 Logix findings and a neuropsychological profile in a young adult with history of traumatic closed head injury. Method 25-year old, right-handed, Caucasian man with no significant medical history prior to sustaining a parenchymal hemorrhage along the left anterior inferior frontal lobe and left temporal lobe, as well as a left anterior frontal subdural hematoma in 2019. The patient reported a premorbid history of generalized anxiety with panic, and elevated emotionality post-injury. Results Estimated premorbid verbal functioning was average, consistent with his score as predicted by demographic variables. The patient exhibited decreased concussion symptom severity and improved cognitive performance across repeat C3 Logix administrations. On comprehensive neuropsychological evaluation, he demonstrated intact performance across cognitive domains, with relative weakness consistent with localization of injury, sustained eye injury, and expected recovery duration. Conclusions Repeat cognitive screenings were generally consistent with comprehensive neuropsychological evaluation results. This case study highlights that the C3 Logix tool should be further considered as a brief cognitive screening measure to inform treatment of traumatic head injuries within a multidisciplinary medical setting.
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Dimopoulos, Meletios A., Antonio Palumbo, Paolo Corradini, Michele Cavo, Michel Delforge, Francesco Di Raimondo, Katja C. Weisel et al. „Safety and efficacy of pomalidomide plus low-dose dexamethasone in STRATUS (MM-010): a phase 3b study in refractory multiple myeloma“. Blood 128, Nr. 4 (28.07.2016): 497–503. http://dx.doi.org/10.1182/blood-2016-02-700872.
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Key Points STRATUS (MM-010), the largest POM + LoDEX trial, confirms the regimen offers clinically meaningful benefit and is generally well tolerated. STRATUS supports POM + LoDEX as a standard of care for patients with RRMM who have poor prognosis and high need for effective treatments.
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Dzelebdzic, Dejan. „Pisma Jovana Apokavka Teodoru Duki“. Zbornik radova Vizantoloskog instituta, Nr. 45 (2008): 126–40. http://dx.doi.org/10.2298/zrvi0845126d.
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(francuski) Durant ses 15 ann?es de r?gne, le souverain d'Epire et plus tard empereur de Thessalonique, Theodore Doukas, fort de ses nombreuses victoires face aux Latins et aux Bulgares lui ayant valu de repousser dans une large mesure les fronti?res de son Etat, a acquis un grand prestige aupr?s de ses sujets. Pourtant, on ne lui conna?t aucun ?loge le c?l?brant comme cela est le cas pour ses homologues, et ce non seulement de la dynastie des Comn?nes et des Anges au XIIe si?cle, mais aussi parmi les Lascaris de Nic?e. Les raisons pour lesquelles la propagande de Th?odore Doukas a omis de recourir a la rh?torique doivent ?tre, a ce qu'il semble, recherch?es dans les circonstances historiques, voire le d?sint?r?t de ce souverain pour cette discipline, et non dans l'absence d'orateurs instruits et de talents. Le r?le d'?crivain aulique aurait pu ?tre endosse, par exemple, par Apokaukos Chomatenos et Georges Bardanes, qui occupaient d'importantes fonctions eccl?siastiques dans l'Etat ?pirote, mais aussi Michel Choniates et Euthyme Tornikes, qui avaient d?j? ?cris des ?loges pour deux empereurs respectivement Isaac II et Alexis III. Toutefois, quand bien m?me la rh?torique n'existait pas en tant qu'?l?ment du c?r?monial aulique en vigueur dans l'Etat ?pirote, elle gardait toute sa place dans les lettres des dignitaires eccl?siastiques ?rudits. Il est ainsi permis de consid?rer que l'absence d'?loges de Th?odore Doukas a ?t?, en partie, compens?e par les lettres que lui a adress?es le m?tropolite de Naupacte, Jean Apokaukos. Sur plus de 150 lettres de sa main, aujourd'hui conserv?es, pas moins de 21 ?taient adress?es au souverain d'Epire. Bien que ces derni?res aient quasiment toujours ?t? r?dig?es pour des raisons pratiques - Apokaukos y exposant des revendications personnelles ou au nom d'autrui - leur partie introductive renferme tr?s r?guli?rement un ?loge de Theodore Doukas qui n'est pas sans rappeler, parfois, les discours ?pidictiques. Une lecture et analyse attentives de ces lettres laissent apparaitre que, des le d?but du r?gne de Theodore Doukas, et au plus tard a partir de 1218, soit avant sa proclamation en tant qu'empereur (1225/26), Apokaukos a soutenu les ambitions imp?riales de ce souverain. Dans la p?riode 1218-1220 on rel?ve plusieurs allusions au fait que Theodore Doukas se verra conf?rer le pouvoir imp?rial par exemple lorsqu'il pr?voit que Theodore rev?tira bient?t les chausses rouges (cf. Epirotica 245.23-24) et qu'il recevra l'onction imp?riale (cf. Epirotica 247.23-27). Plus encore, durant cette m?me p?riode, et ce a deux reprises, Apokaukos appelle explicitement Theodore Doukas notre empereur, une premi?re fois dans une lettre adress?e a Theodore lui-m?me (cf. NP 271.11-20) et une seconde fois dans une lettre adress?e au patriarche de Nic?e, Manuel Ier, en 1222 (cf. Epirotica 272.30-31). N?anmoins, ce n'est qu'avec la proclamation de Theodore Doukas en tant qu'empereur que les lettres d'Apokaukos rev?tent le ton d'enkomia du souverain ?pirote, ce qu'Apokaukos annonce lui-m?me dans sa premi?re lettre adress?e a Theodore imm?diatement ?pres sa proclamation en tant qu'empereur (cf. NP 289.24-31). A partir de cet instant, lorsqu'il s'adresse directement a l'empereur, il emploie le terme de basileus, ce qui n'a jamais ?t? le cas auparavant. Parall?lement, on note l'apparition de plusieurs lieux communs, caract?ristiques des ?loges adresses aux empereurs, jusqu'alors absents dans ses lettres. Apokaukos, par exemple exprime sa crainte que son art de la rh?torique ne soit pas suffisant pour louer, comme il se doit, les vertus de l'empereur (cf. Bees 77.25-31) Theodore Doukas est compare aux empereurs ant?rieurs, en affirmant qu'il a surpasse tous ses pr?d?cesseurs par sa vertu et ses actes (cf. Bees 69) l'empereur de Thessalonique est compare au Christ (cf. Bees 71.1-3) et aux guides v?t?rotestamentaires du peuple ?lu. Enfin, Apokaukos introduit alors un nouveau motif exprimant l'espoir que Theodore Doukas lib?rera Constantinople et recouvrera le tr?ne imp?rial. .
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Baskoutas, I., G. A. Papadopoulos, V. Karakostas und E. Papadimitriou. „Recent 2005-2006 strong seismic activity in Greece under the aspect of seismicity parameters temporal variation analysis“. Bulletin of the Geological Society of Greece 40, Nr. 3 (05.06.2018): 1055. http://dx.doi.org/10.12681/bgsg.16824.
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Recent strong seismic excitation (2005-2006), which occurred at the northwestern part of the Hellenic arc and north ofSamos Island close to the coasts of the Asia Minor, is investigated under the aspect of temporal variation seismicity profile of activated seismic zones. Seismicity profile is constructed by the means ofther FastBEE analysis introduced recently. Seismicity parameters considered in this study are b-value, energy releasee in the form logE2/3 and the quantity logNofthe cumulative number of events, in the examined area. Due to homogeneity and completeness reasons, the earthquakes with magnitudes Mi>3.0 since 1990 from the earthquake catalogue of the Geodynamic Institute of the National Observatory of Athens, is used to perform the present analysis in both areas. Temporal variation profiles for both areas show a remarkable fluctuation around their mean value and specifically above the limits of the calculated standard errors behaviour forming a temporal pattern, which can be attributed to earthquake preparation process. In this temporal pattern, b value, which is related to the seismogenic process in many previous studies all over the world shows a tendency to increase and then to decrease before the occurrence of a strong earthquake, and at the same time the quantity logE 3 shows a tendency to decrease and then to increase before the strong event occurrence Mis identification of such a clear pattern for a period of time can be attributed to the lack of adequate data.
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Weisel, Katja C., Meletios A. Dimopoulos, Philippe Moreau, Martha Lacy, Kevin W. Song, Michel Delforge, Lionel Karlin et al. „Pomalidomide plus low-dose dexamethasone (POM + LoDEX) versus high-dose dexamethasone (HiDEX) in relapsed/refractory multiple myeloma (RRMM): MM-003 analysis of patients (pts) with moderate renal impairment (RI).“ Journal of Clinical Oncology 31, Nr. 15_suppl (20.05.2013): 8527. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.8527.
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8527 Background: Pts who have exhausted lenalidomide (LEN) and bortezomib (BORT) treatment (Tx) have a poor prognosis. A significant proportion of pts have RI with increasing incidence during disease course. POM + LoDEX has demonstrated efficacy in pts with prior LEN and BORT, including those with RI. MM-003 is an open-label, multicenter, phase 3 trial comparing POM + LoDEX vs HiDEX in RRMM pts who failed LEN and BORT and progressed on their last Tx. Methods: Pts must have failed LEN and BORT after ≥ 2 consecutive cycles of each (alone or in combination) and must have been refractory to last prior Tx (progressive disease [PD] during Tx or within 60 days). Pts with creatinine clearance (CrCl) < 45 mL/min were excluded. Randomization was 2:1 to POM 4 mg D1–21 + DEX 40 mg (20 mg for pts aged > 75 y) qw; or DEX 40 mg (20 mg for pts aged > 75 y) D1–4, 9–12, and 17–20 (28-D cycles). Tx continued until PD or unacceptable adverse event (AE). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and AEs. This analysis examined pts with or without moderate RI (CrCl < 60 vs ≥ 60mL/min). Results: 302 pts received POM + LoDEX; 153 pts received HiDEX, 31% and 39% had moderate RI, respectively. Pts with moderate RI were more likely to be older (64% vs 36% aged > 65 y) vs no RI. Median follow-up was 4 mo. Median PFS and OS were significantly longer with POM + LoDEX vs HiDEX regardless of RI (Table). Similar AE rates for POM + LoDEX as well as HiDEX Tx were seen in pts with and without moderate RI (Table). Discontinuation due to AE was 5% vs 7% (no moderate RI) and 11% vs 5% (moderate RI). Conclusions: POM + LoDEX significantly extended PFS and OS vs HiDEX in pts with or without moderate RI. Tolerability of POM + LoDEX was acceptable across subgroups, with few discontinuations due to AE. Clinical trial information: NCT01311687. [Table: see text]
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Song, Kevin W., Meletios A. Dimopoulos, Katja C. Weisel, Philippe Moreau, Martha Lacy, Michel Delforge, Lionel Karlin et al. „Quality of life (QOL) improvements for pomalidomide plus low-dose dexamethasone (POM + LoDEX) in relapsed and refractory multiple myeloma (RRMM) patients (pts) enrolled in MM-003.“ Journal of Clinical Oncology 31, Nr. 15_suppl (20.05.2013): 8583. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.8583.
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8583 Background: Poor prognosis and therapy exhaustion have been associated with reduced QOL in RRMM. In MM-003, a randomized, multicenter, open-label phase 3 trial, POM + LoDEX (n = 302) significantly improved progression-free and overall survival vs. high-dose dexamethasone (HiDEX; n = 153) in pts who failed lenalidomide (LEN) and bortezomib (BORT) and progressed on their last therapy. This analysis evaluated QOL changes in these pts. Methods: To assess pt-reported outcomes, cross-sectional and longitudinal analyses were performed. Minimal important differences for 5 clinically relevant EORTC QLQ-C30 domains (Global Health Status, Physical Functioning, Fatigue, Emotional Functioning, and Pain) were calculated as meaningful change thresholds (1 standard error of measurement) from baseline through cycle (C) 5. Time to QOL worsening was compared between arms using the Kaplan-Meier method. Results: Favorable trends were observed for POM + LoDEX vs. HiDEX in each of the 5 relevant domains. The cross-sectional analysis indicated statistically or marginally significant (P < .10) differences favoring POM + LoDEX in Global Health Status (C2, 4), Physical Function (C2, 3, 4), Emotional Function (C2, 3, 4), and Fatigue (C2) scores. Longitudinal comparisons between arms confirmed the significance of score changes for Global Health Status (C2; P = .01), Physical Functioning (C3 and 4; P = .018 and .028, respectively), Emotional Functioning (C3; P = .018), and Fatigue (C5; P = .008) for POM + LoDEX vs. HiDEX. HiDEX pts exhibited clinically meaningful worsening in Global Health Status and Physical Functioning scores vs. POM + LoDEX by C2 (P = .04) and C3 (P = .02), respectively. POM + LoDEX extended median time to meaningful worsening vs. HiDEX for Global Health Status (114 vs. 85 days, P = .05), Physical Functioning (174 vs. 106 days; P = .09), Fatigue (113 vs. 60 days; P = .02), Emotional Functioning (190 vs. 124 days; P = .04), and Pain (147 vs. 113 days; P = .2). Conclusions: In heavily pretreated pts who failed LEN and BORT, POM + LoDEX resulted in better clinical outcomes as well as improvement in clinically relevant QOL measurements over the course of treatment. Clinical trial information: NCT01311687.
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Jagannath, Sundar, Craig C. Hofmeister, David S. Siegel, Ravi Vij, Sagar Lonial, Kenneth C. Anderson, Min Chen, Mohamed Zaki und Paul G. Richardson. „Pomalidomide (POM) with Low-Dose Dexamethasone (LoDex) in Patients (Pts) with Relapsed and Refractory Multiple Myeloma Who Have Received Prior Therapy with Lenalidomide (LEN) and Bortezomib (BORT): Updated Phase 2 Results and Age Subgroup Analysis“. Blood 120, Nr. 21 (16.11.2012): 450. http://dx.doi.org/10.1182/blood.v120.21.450.450.
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Abstract Abstract 450 Background: New antimyeloma treatments that re-establish tumor response are required to improve survival for pts with advanced, treatment-refractory MM. The MM-002 phase 2 study evaluated the safety and efficacy of oral pomalidomide, in combination with low-dose dexamethasone (POM+LoDex), in pts with relapsed and refractory multiple myeloma (RRMM) who have who have received ≥2 prior therapies including LEN and BORT (Richardson PG, et al. Blood 2011;118:abs 634). Updated results from March 2012 for pts and the outcomes of subgroup analyses are presented. Methods: Eligible pts with MM who had received at least 2 prior therapies (including LEN and BORT) and had disease progression within 60 days of their last treatment were randomized (1:1 ratio) to either POM+LoDEX (POM, 4 mg/day for days 1–21 of a 28-day cycle; LoDex, 40 mg/week) or POM alone. At progression, pts receiving POM alone could receive POM+LoDEX at investigator's discretion. Pts aged over 75 years received LoDex, 20 mg/week. All pts received mandatory thromboprophylaxis (daily low-dose aspirin). Pts were stratified within each treatment group according to age. The key efficacy endpoints included the objective response rate using European Bone Marrow Transplantation (EBMT) criteria, duration of response, progression free survival (PFS) and overall survival (OS), and safety. This updated analysis focused on pts on the POM+LoDex arm. Results: The intention-to-treat efficacy analysis included 113 pts in the POM+LoDex group. The mean age of pts treated with POM+LoDex was 64 years (range, 34–88); 99 pts (88%) were aged ≤75 years. Response rates, median duration of response, and age subgroups are presented in the Table. Median PFS and OS were 4.6 months (mos) and 16.5 mos, respectively, in the POM+LoDex group overall. In the age subgroup analysis of pts treated with POM+LoDex, the median PFS was 4.7 mos in pts aged ≤65 years, and 3.7 mos in pts >65 years. Median OS was 19.7 mos in pts aged ≤65 years and 11.8 mos in pts >65 years. The most common grade 3 or 4 adverse events (AEs) occurring in >5% of pts were neutropenia (41%), anemia (22%), pneumonia (22%), thrombocytopenia (19%), fatigue (14%), dyspnea (13%), leukopenia (10%), back pain (10%), and urinary tract infection (9%). AEs led to at least one dose reduction in 26% of pts; neutropenia was associated with a dose reduction in 4% of pts. Overall, 78% of pts who developed grade 3 or 4 neutropenia used G-CSF during study treatment. There were no reports of grade 3 or 4 peripheral neuropathy (PN); grade 1 or 2 PN occurred in 7% of pts treated with POM+LoDex. Deep vein thrombosis (any grade) occurred in 2 pts (2%), both aged ≤65 years. Grade 3 or 4 neutropenia occurred in 46% of pts aged ≤65 years and in 35% of pts aged >65 years. Despite this, only 1 pt in each age group developed febrile neutropenia (2%). The mean relative dose intensity (dose intensity/planned dose intensity) was 0.9 in both pt groups of ≤65 years and > 65 years receiving POM+LoDex. Overall, 21 pts (19%) of the POM+LoDex group died during the study. The most common cause of death was progressive MM (52%; only in 14% of all cases was it due to disease progression); other causes of death (48%) included infections, cerebral/intracranial/subarachonoid hemorrhage, acute respiratory distress syndrome, and suicide in one pt with a history of severe depression. Conclusions: POM, 4 mg/day for days 1–21 of a 28-day cycle in combination with LoDex, is clinically effective and generally well tolerated in pts with RRMM who have received multiple prior treatments including LEN and BORT. POM+LoDex represents an important potential new treatment option for pts with advanced MM and appears active in both younger and older pts, with tolerability similar across different age groups. Phase 3 studies of POM+LoDEX in combination with other agents (e.g. bortezomib) are ongoing. Disclosures: Jagannath: Millennium Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck Sharp & Dohme: Honoraria, Membership on an entity's Board of Directors or advisory committees; Onyx Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Off Label Use: Pomalidomide is an investigational drug and is not approved for the treatment of patients with any condition. Hofmeister:Celgene: Advisory Board Other, Honoraria. Siegel:Onyx: Advisory Board, Advisory Board Other, Honoraria, Speakers Bureau; Millennium Pharma: Advisory Board, Advisory Board Other, Honoraria, Speakers Bureau; Celgene: Advisory Board Other, Honoraria, Speakers Bureau; Merck: Advisory Board, Advisory Board Other, Honoraria, Speakers Bureau. Vij:Onyx: Consultancy, Research Funding; Millennium Pharma: Speakers Bureau; Celgene: Consultancy, Research Funding, Speakers Bureau. Lonial:Millennium, Celgene, Novartis, BMS, Onyx, Merck; all < $10,000 per year and disclosed to my institution: Consultancy. Anderson:Acetylon, Oncopep: Scientific Founder, Scientific Founder Other; Celgene, Millennium, BMS, Onyx: Membership on an entity's Board of Directors or advisory committees. Chen:Celgene: Employment, Equity Ownership. Zaki:Celgene: Employment, Equity Ownership. Richardson:Celgene, Millennium, Johnson & Johnson: Advisory Board Other.
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Schmidt, Hans-Martin. „Die Guyonsche Loge“. Cells Tissues Organs 131, Nr. 2 (1988): 113–21. http://dx.doi.org/10.1159/000146497.
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Hivert-Messeca, Yves. „Dieu en Loge“. La chaîne d'union N° 39, Nr. 1 (01.01.2007): 48–59. http://dx.doi.org/10.3917/cdu.039.0048.
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Morris, C. A., A. Bisset, A. Vlassoff, C. J. West und M. Wheeler. „Genetic parameters forNematodirusspp. egg counts in Romney lambs in New Zealand“. Animal Science 79, Nr. 1 (April 2004): 33–39. http://dx.doi.org/10.1017/s1357729800054503.
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AbstractGenetic analyses were carried out on Nematodirus spp. egg counts (NEM) of lambs from a set of Romney breeding lines. The lines had been under selection for 22 seasons (1979 to 2000) for divergence in resistance to infection by strongyle nematodes other than NEM, using faecal egg count (FEC) as the selection criterion. Heritabilities and genetic correlations for NEM were estimated using residual maximum likelihood procedures. Correlated responses in NEM were also determined. Heritability estimates for loge(NEM + 100) in lambs at 4 months of age (NEM1) or 6 months of age (NEM2) were 0·15 (s.e. 0·03) and 0·26 (s.e. 0·04) respectively (c.f. 0·28 (s.e. 0·02) and 0·35 (s.e. 0·02) for loge(FEC + 100)). The genetic correlation between loge(NEM1 + 100) and loge(NEM2 + 100) was 0·85 (s.e. 0·08), while the genetic correlations between measurements of loge(NEM + 100) and loge(FEC + 100) on both sampling occasions had a weighted average of 0·43, with estimates ranging from 0·30 (s.e. 0·08) to 0·52 (s.e. 0·07). Divergence in loge(NEM + 100) between the high and low FEC lines, estimated over both sampling times combined, was 1·07 phenotypic standard deviations, compared with 3·6 phenotypic standard deviations for loge(FEC + 100). Expressed in terms of back-transformed eggs per g, the high and low FEC lines differed by factors of 7·6 and 32·2 for NEM and FEC, respectively. The results support earlier parasitological data indicating that the genetic mechanisms in sheep which are responsible for resistance to other strongyle nematodes probably also influence resistance to Nematodirus infection.
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Mushtaq, Adeela, Ahmad Iftikhar, Midhat Lakhani, Fnu Sagar, Ahmad Kamal, Umar Zahid, Hamza Hassan et al. „Pomalidomide Based Regimens for Treatment of Relapsed Multiple Myeloma: A Systematic Review and Meta-Analysis of Clinical Trials“. Blood 132, Supplement 1 (29.11.2018): 2022. http://dx.doi.org/10.1182/blood-2018-99-111439.
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Abstract Introduction Bortezomib, a proteasome inhibitor and lenalidomide (Len), an immunomodulatory drug are the backbone of established treatment regimens for newly diagnosed MM. Patients with dual-refractory (refractory to both bortezomib and lenalidomide) disease have a poor prognosis with overall survival estimated to be less than one year. Pomalidomide (Pom) has distinct anticancer, antiangiogenic and immunomodulatory properties and has demonstrated synergistic antiproliferative activity in combination regimens. The aim of our study is to compare different Pom based regimens to identify the most effective regimen for relapsed refractory multiple myeloma (RRMM) patients. Methods A comprehensive literature search was performed on PubMed, Cochrane library, Web of Science, Embase and AdisInsight databases on 03/29/2018 which identified a total of 1374 studies. We included phase II/III clinical trials on pomalidomide based regimens that have clearly documented efficacy outcomes. All statistical analyses were performed using Comprehensive Meta-analysis (CMA) Version 3. We used the Cochrane Q statistics (p<0.05 considered significant) and I2 index to calculate the degree of heterogeneity of the studies. A random effect model was used if there was significant heterogeneity (p>0.05 or I2 >50%). Studies were classified into subgroups according to the therapeutic regimen: dual and triplet combinations. A separate stratified analysis of triplet regimens based on type of regimen was also performed. Results A total of 35 studies (n = 4623 patients) were included. The most commonly studied regimen was Pom + LoDex (Low dose dexamethasone) with a total of 16 studies on this regimen. All patients included in our study had ≥ 2 prior lines of therapy. Mean number of prior lines of therapy was 6. Most patients were lenalidomide refractory, with 10 patient cohorts of 100% refractoriness and 8 cohorts of ≥ 90% refractoriness. Pooled analysis showed an overall response rate (ORR) of 47.1% across all Pom regimens including both doublet and triplet regimens. An I2 value of 87.3 was found, indicating high heterogeneity across all Pom regimens. With Pom-LoDex, pooled ORR was found to be 35.7% and mean OS 14.37 months. With triplet regimens, pooled ORR was found to be 61.9%. In a separate stratified analysis of triplet regimens based on type of regimen, pooled ORRs with few selected regimens were as follows; Bort-Pom-LoDex (pooled ORR 83.5%, mean PFS 15.7 months [mos]), CFZ-Pom-LoDex (pooled ORR 77.1%, mean PFS 15.3 mos), Pom-LoDex-bendamustine (pooled ORR 74.2%), Pom-Dex-daratumumab (pooled ORR 64.5%), Pom-LoDex-cyclophosphamide (pooled ORR 59.4%, mean PFS 9.5 mos), Pom-LoDex-doxorubicin (pooled ORR 32%). Most frequently reported adverse event with Pom based regimens was myelosuppression. Mean incidences of grade ≥3 hematologic adverse events were neutropenia (47.6%), anemia (26.5%), and thrombocytopenia (20.8%). Mean incidences of grade ≥3 non-hematologic adverse events were infections (29.1%), pneumonia (13.8%) and fatigue (10%). Most of the studies used pomalidomide 4mg daily dosing. Lacy et al. suggested no advantage of 4mg pomalidomide over 2 mg daily dosing. Conclusion From results of pooled analysis, we can infer that triplet combinations of Pom yield almost double response rates (pooled ORR 61.9%) when compared to dual combination of Pom-LoDex (pooled ORR 35.7%). Among three drug combinations, Bort-Pom-LoDex (pooled ORR 83.5%) and CFZ-Pom-LoDex (pooled ORR 77.1%) seem to produce better outcomes. Our study provides useful insight into relative efficacy of various Pom regimens for treatment of RRMM patients. Several trials involving various MoAbs like nivolumab, daratumumab, elotuzumab, isatuximab and pembrolizumab in combination with Pom-LoDex are currently ongoing. Pomalidomide has an acceptable safety profile. Most common treatment emergent adverse events were myelotoxicity and infections that can be effectively managed with supportive care and dose modifications. Disclosures No relevant conflicts of interest to declare.
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Weisel, Katja, Jesús F. San Miguel, Kevin W. Song, Michel Delforge, Lionel Karlin, Hartmut Goldschmidt, Philippe Moreau et al. „MM-003 Phase 3 Study Of Pomalidomide In Combination With Low-Dose Dexamethasone (POM + LoDEX) Vs High-Dose Dexamethasone (HiDEX) In Relapsed/Refractory Multiple Myeloma (RRMM): POM + Lodex Is Beneficial For Elderly Patients (> 65 Years of Age)“. Blood 122, Nr. 21 (15.11.2013): 3198. http://dx.doi.org/10.1182/blood.v122.21.3198.3198.
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Abstract Background RRMM patients (pts) who have exhausted bortezomib (BORT) and lenalidomide (LEN) or thalidomide treatment (Tx) have short overall survival (OS; Kumar, 2012). MM pt survival decreases with increased age (Pulte, 2011). POM is a distinct oral IMiD® immunomodulatory agent with direct anti-myeloma, stromal cell–support inhibition, and immune-modulation activities (Quach, 2010). The US FDA approved POM for the Tx of pts who have received ≥ 2 prior Tx, including LEN and BORT, and have demonstrated disease progression (PD) on or within 60 days of completion of the last line of Tx. POM + LoDEX has demonstrated clinical benefit in pts aged ≤ 65 y and > 65 y (Jagannath, EHA 2013; Leleu, 2013). The randomized phase 3 study MM-003 demonstrated significant progression-free survival (PFS) and OS benefits for POM + LoDEX vs HiDEX, despite half of HiDEX pts subsequently receiving POM (San Miguel, EHA 2013). This analysis examined outcomes based on age (≤ 65 y vs > 65 y). Methods Pts had to be refractory to last prior Tx (PD during Tx or within 60 days) and exhausted BORT and LEN after ≥ 2 consecutive cycles of each (alone or in combination). Pts were randomized 2:1 to receive 28-day cycles of POM 4 mg D1-21 + DEX 40 mg (20 mg for pts aged > 75 y) weekly or DEX 40 mg (20 mg for pts aged > 75 y) D1-4, 9-12, and 17-20. HiDEX was chosen as the comparator to isolate the effects of POM as at the time of trial design, it was the standard salvage Tx for heavily pretreated pts. Tx continued until PD or unacceptable toxicity. The primary endpoint was PFS. Secondary endpoints included OS, overall response rate (ORR; ≥ partial response), and safety. Results 455 pts were randomized to POM + LoDEX (n = 302) or HiDEX (n = 153). 45% (135/302) of POM + LoDEX pts and 47% (72/153) of HiDEX pts were aged > 65 y. Since only 8% of POM + LoDEX and HiDEX pts were aged > 75 y, this analysis focused on pts aged ≤ 65 y vs > 65 y. Pts aged ≤ 65 y were more likely to have prior stem cell transplant (91% vs 45%), better renal function (creatinine clearance [CrCl] ≥ 60 mL/min: 78% vs 51%), and less advanced disease (ISS stage III: 28% vs 38%) vs pts aged > 65 y. For pts aged > 65 y, HiDEX pts were less likely to have CrCl ≥ 60 mL/min vs POM + LoDEX (43% vs 55%). All groups had a median of 5 prior Tx. Median follow-up was 10 mos. POM + LoDEX significantly extended PFS vs HiDEX in all pts, with similar benefits observed for pts aged ≤ 65 y or > 65 y (Table). For all pts, OS was significantly longer for POM + LoDEX vs HiDEX, with favorable results for POM + LoDEX in both age subgroups despite a large proportion of HiDEX pts subsequently receiving POM (Table). ORR was significantly higher for POM + LoDEX vs HiDEX in all pts and both age groups (Table). Median duration of POM Tx was similar in pts aged ≤ 65 y (4.4 mos) and > 65 y (4.0 mos). The most common grade 3/4 adverse events (AEs) for pts aged ≤ 65 y (POM + LoDEX vs HiDEX) were neutropenia (50% vs 20%), anemia (35% vs 39%), and infections (31% vs 19%). Neutropenia (45% vs 11%), anemia (30% vs 34%), and infections (30% in both arms) were also the most frequent grade 3/4 AEs for pts aged > 65 y. Grade 3/4 DVT/PE was infrequent (POM + LoDEX vs HiDEX): 1% vs 0% (≤ 65 y) and 1% vs 0% (> 65 y). Grade 3/4 peripheral neuropathy was also infrequent: 1% vs 2% (≤ 65 y) and 1% vs 0% (> 65 y). Discontinuation due to AE was low in pts aged ≤ 65 y (POM + LoDEX: 6%; HiDEX 10%) and > 65 y (POM + LoDEX: 12%; HiDEX: 11%). Importantly, the median relative POM dose intensity was consistent at 90% for both age groups. Conclusion POM + LoDEX significantly extended PFS, with comparable benefits across age groups (approximately 50% reduction in rate of progression). OS results were similar to that of the overall pt population, and favored POM + LoDEX in both age groups. Tolerability profiles were consistent for pts ≤ 65 y or > 65 y. POM at 4 mg appears to be a feasible starting dose for pts aged > 65 y. These data support considering POM + LoDEX as a standard Tx option in RRMM pts regardless of age. Disclosures: Weisel: Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria. Off Label Use: POM is approved in the US but not in Europe. San Miguel:Onyx: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Millenium: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees. Song:Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Research Funding, Speakers Bureau. Delforge:Celgene: Honoraria. Karlin:Celgene: Export board committee Other, Honoraria; Janssen: Honoraria. Goldschmidt:Novartis: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Moreau:Celgene: Honoraria, Speakers Bureau. Oriol:Celgene: Consultancy. Cavo:Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Onyx: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Millennium: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees. Alegre:Janssen: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Martinez-Lopez:Celgene: Honoraria, Research Funding. Chen:Celgene: Consultancy, Honoraria, Research Funding. Knop:Celgene: Honoraria. Yu:Celgene: Employment, Equity Ownership. Watkins:Celgene: Employment, Equity Ownership. Sternas:Celgene: Employment, Equity Ownership. Jacques:Celgene: Employment, Equity Ownership. Zaki:Celgene: Employment, Equity Ownership. Dimopoulos:Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees.
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Richardson, Paul G., David S. Siegel, Ravi Vij, Craig C. Hofmeister, Sundar Jagannath, Christine Chen, Sagar Lonial et al. „Randomized, Open Label Phase 1/2 Study of Pomalidomide (POM) Alone or in Combination with Low-Dose Dexamethasone (LoDex) in Patients (Pts) with Relapsed and Refractory Multiple Myeloma Who Have Received Prior Treatment That Includes Lenalidomide (LEN) and Bortezomib (BORT): Phase 2 Results“. Blood 118, Nr. 21 (18.11.2011): 634. http://dx.doi.org/10.1182/blood.v118.21.634.634.
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Abstract Abstract 634 Background: Pts with relapsed/refractory multiple myeloma (RRMM), resistant to LEN and BORT, have poor outcomes. POM (2 or 4 mg/d for 28 d of each 28-d cycle) is an immunomodulatory compound with activity in pts refractory to both LEN and BORT (Lacy MQ et al. Blood 2011;doi:10.1182). This multicenter phase 1/2 study investigated the safety and efficacy of POM alone or in combination with LoDex (POM+LoDex) for treatment of pts with RRMM who had received both BORT and LEN. Phase 1 identified 4 mg/d of POM as the recommended dose for phase 2 (Richardson PG et al. Blood 2010;116:Abs 864). Phase 2 results are presented. Methods: Pts with RRMM after ≥ 2 prior regimens, including ≥ 2 cycles of LEN and BORT separately or in combination, were eligible. Pts had to have progressed ≤ 60 d of their last treatment prior to study entry (refractory disease). This analysis evaluated the efficacy and safety of POM+LoDex (POM 4 mg/d 1–21 d of each 28-d cycle; Dex 40 mg/wk) and POM alone in a randomized open-label study. Results presented here were based on investigator assessed responses for the intent-to-treat population. Responses were independently adjudicated. The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response (partial response [PR] or ≥ PR), duration of response (DOR), overall survival (OS), and safety. All pts received daily low-dose aspirin thromboprophylaxis. Results: A total of 221 pts were enrolled in phase 2 (POM+LoDex n = 113; POM n = 108); 219 received ≥ 1 cycle of study treatment and 191 pts were evaluable for response. Baseline characteristics were comparable between the two arms with a median of 5 (range 2–13) prior therapies in both arms; 74% of pts in POM+LoDex and 76% of pts in POM alone had prior autologous stem-cell transplantation (ASCT). The remaining pts were elderly (aged > 75 yrs) or ineligible for ASCT; all pts were exposed to corticosteroids and 84% in the POM+LoDex and 95% in POM alone arms were exposed to alkylators. Pts were refractory to LEN (POM+LoDex 77% and POM alone 79%), BORT (73% and 69%), or both drugs (61% and 59%). Among pts who were randomized to receive POM alone, 61 (56%) subsequently went on to receive POM+LoDex due to progressive disease (PD) per protocol. A median of 5 (range 1–17) treatment cycles were received by pts in both arms. Median treatment duration was 5.0 mos. Response of ≥ PR was seen in 34% of pts in the POM+LoDex arm and 13% in the POM alone arm, including 1% complete response (CR) in each arm; ≥ minor response (MR) was 45% vs 29%, respectively. Median DOR was 7.7 mos with POM+LoDex and 8.3 mos with POM alone, and median PFS was 4.6 mos and 2.6 mos, respectively (Fig 1). Median OS was comparable for both arms (14.4 and 13.6 mos). Results from independent adjudication were similar, with ≥ PR in 30% of pts in the POM+LoDex arm and 9% in the POM alone arm, including 1% and 0% CR, respectively, in each arm. ≥ MR was achieved with POM+LoDex in 45% and with POM alone in 25%; PFS was 3.8 mos and 2.5 mos, respectively. In the subgroup of pts refractory to both LEN and BORT, 30% and 16% of pts treated with POM+LoDex or POM alone, respectively, achieved ≥ PR; ≥ MR was 45% and 30%, respectively. Median PFS was 3.8 mos for POM+LoDex and 2.0 mos for POM alone; median OS showed a similar trend (13.5 and 10.8 mos, respectively). The main reason for treatment discontinuation was PD in both arms (POM+LoDex 51%; POM alone 44%); discontinuations due to adverse events (AEs) were 7% and 12%, respectively. Grade 3/4 AEs in POM+LoDex vs POM alone, respectively, were: neutropenia 38% and 47%; febrile neutropenia 2% and 2%; thrombocytopenia 19% and 21%; anemia 21% and 17%; pneumonia 19% and 8%; and fatigue 10% and 8%. All grades of peripheral neuropathy, deep vein thrombosis, and renal failure occurred in 7% and 10%, 2% and 1%, and 2% and 1% of pts for POM+LoDex vs POM alone, respectively. Conclusions: POM (4 mg/d 1–21 d of each 28-d cycle) with or without LoDex demonstrates clinical activity and is generally well tolerated in pts with advanced MM who have received multiple prior therapies and are refractory to both LEN and BORT. Prospective comparison indicates that POM+LoDex is associated with greater clinical benefit and no increased toxicity vs POM alone. This is supported by high response rates, long DOR, and PFS benefit achieved with POM+LoDex. The regimen is now being investigated both in phase 3 trials, and as part of combination treatment including with BORT. Disclosures: Richardson: Millennium Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees. Off Label Use: Pomalidomide is a new treatment for multiple myeloma. Siegel:Celgene Corporation: Honoraria, Research Funding, Speakers Bureau. Vij:Celgene: Consultancy, Research Funding, Speakers Bureau. Jagannath:PER Group: Honoraria; J & J Pharm: Membership on an entity's Board of Directors or advisory committees; Envision Communication: Honoraria, Membership on an entity's Board of Directors or advisory committees; Imedex: Honoraria; Dava Oncology: Membership on an entity's Board of Directors or advisory committees; Merck Sharp & Dohme: Investigators meeting; Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jansen Pharmaceuticals: Honoraria; Medicom Worldwide: Membership on an entity's Board of Directors or advisory committees. Chen:Celgene Corporation: Consultancy, Honoraria, Research Funding. Lonial:Celgene Corporation: Consultancy; Millennium Pharmaceuticals: Consultancy; Novartis: Consultancy; Bristol-Myers Squibb: Consultancy; Onyx: Consultancy; Merck: Membership on an entity's Board of Directors or advisory committees. Jakubowiak:Ortho Biotech: Consultancy, Honoraria, Speakers Bureau; Celgene Corporation: Consultancy, Honoraria, Speakers Bureau; Millennium Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Onyx Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Exelixis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Bahlis:Celgene Corporation: Consultancy, Honoraria, Research Funding, Speakers Bureau. Baz:BMS: Research Funding; Millennium: Research Funding; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding. Larkins:Celgene Corporation: Employment. Chen:Celgene Corporation: Employment. Zaki:Celgene Corporation: Employment. Anderson:Acetylon Pharmaceuticals: Consultancy, Equity Ownership; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Millennium Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Onyx: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Merck: Membership on an entity's Board of Directors or advisory committees.
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Goldschmidt, Hartmut, Meletios A. Dimopoulos, Katja C. Weisel, Philippe Moreau, Martha Lacy, Kevin W. Song, Michel Delforge et al. „Pomalidomide plus low-dose dexamethasone (POM + LoDEX) versus high-dose dexamethasone (HiDEX) in relapsed/refractory multiple myeloma (RRMM): Impact of cytogenetics in MM-003.“ Journal of Clinical Oncology 31, Nr. 15_suppl (20.05.2013): 8528. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.8528.
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8528 Background: RRMM patients (pts) who fail lenalidomide (LEN) and bortezomib (BORT) have poor prognosis. High-risk cytogenetics predict shorter survival. POM + LoDEX has demonstrated efficacy in pts with prior LEN and BORT and high-risk cytogenetics. MM-003 is an open-label, multicenter, phase III trial comparing POM + LoDEX vs. HiDEX in RRMM pts who failed LEN and BORT treatment (Tx) and have progressed on their last therapy. Methods: Pts must have been refractory to the last prior Tx (progressive disease [PD] during or within 60 days) and failed LEN and BORT after ≥ 2 consecutive cycles of each (alone or in combination). Randomization was 2:1 to POM 4 mg D1–21 + DEX 40 mg (20 mg for pts aged > 75 y) weekly; or DEX 40 mg (20 mg for pts aged > 75 y) D1–4, 9–12, and 17–20 (28-day cycles). Tx continued until PD or unacceptable adverse events (AEs). The primary endpoint was progression-free survival (PFS). Secondary endpoints included OS and AEs. This analysis examined pts meeting modified high-risk cytogenetic criteria—del(17p13) and/or t(4p16/14q32). Results: 302 pts received POM + LoDEX, and 153 pts received HiDEX. 225 and 107 pts, respectively, were evaluable for cytogenetics. Baseline characteristics were similar. Median PFS and OS were significantly longer with POM + LoDEX vs. HiDEX, regardless of cytogenetic risk (Table). The most common grade 3/4 AEs were neutropenia, anemia, and infection (Table). Discontinuation due to AE was low: 4% vs. 6% (high risk) and 10% vs. 4% (standard risk). Conclusions: Median PFS and OS were significantly longer with POM + LoDEX vs. HiDEX in pts with cytogenetically-defined high-risk disease, consistent with results from the intent-to-treat population. Tolerability was acceptable. POM + LoDEX should be considered a new Tx option in pts failing LEN and BORT. Clinical trial information: NCT01311687. [Table: see text]
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San-Miguel, Jesùs F., Katja C. Weisel, Philippe Moreau, Martha Lacy, Kevin W. Song, Michel Delforge, Lionel Karlin et al. „MM-003: A phase III, multicenter, randomized, open-label study of pomalidomide (POM) plus low-dose dexamethasone (LoDEX) versus high-dose dexamethasone (HiDEX) in relapsed/refractory multiple myeloma (RRMM).“ Journal of Clinical Oncology 31, Nr. 15_suppl (20.05.2013): 8510. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.8510.
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8510 Background: RRMM patients (pts) who have exhausted treatment (Tx) with bortezomib (BORT) and lenalidomide (LEN) or thalidomide have a poor prognosis with short overall survival (OS). HiDEX is a well-established standard Tx in RRMM. POM has demonstrated clinical efficacy in pts refractory to LEN and BORT. MM-003 compared POM + LoDEX vs. HiDEX in RRMM pts who failed LEN and BORT and who progressed on their last Tx. Methods: Pts must have been refractory to last prior Tx (progressive disease [PD] during Tx or within 60 days) and failed LEN and BORT after ≥ 2 consecutive cycles of each (alone or in combination). Pts were randomized 2:1 to receive 28-day cycles of POM 4 mg D1–21 + DEX 40 mg (20 mg for pts aged > 75 y) weekly or DEX 40 mg (20 mg for pts aged > 75 y) D1–4, 9–12, and 17–20. Tx continued until PD or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included OS, overall response rate (ORR; ≥ partial response), and safety. Analyses were based on intent to treat. Results: 455 pts were randomized to POM + LoDEX (n = 302) or HiDEX (n = 153). The median number of prior Tx was 5 (range 1-17). 72% were refractory to LEN and BORT. Median follow-up was 4 months. POM + LoDEX significantly extended median PFS (3.6 vs. 1.8 months, HR = 0.45, P < .001) and OS (not reached vs. 7.8 months, HR = 0.53, P < .001) vs. HiDEX. The OS benefit was observed despite 29% of HiDEX pts receiving POM after PD. The trial met the primary endpoint of PFS, crossed the upper boundary for OS superiority, and the Data Monitoring Committee recommended crossover from HiDEX to POM ± DEX. With updated data, the ORR was 21% for POM + LoDEX vs. 3% for HiDEX (P < .001) and 24% vs 3% for pts randomized ≥ 6 months post-enrollment (P < .001). The most frequent grade 3/4 adverse events (AEs) for POM + LoDEX vs. HiDEX were neutropenia (42% vs. 15%), anemia (27% vs. 29%), and infection (24% vs. 23%). Discontinuation due to AEs was infrequent (7% vs. 6%). Updated data will be presented. Conclusions: POM + LoDEX significantly extended PFS and OS vs. HiDEX in pts who failed LEN and BORT. POM + LoDEX should become a standard of care in RRMM pts who have exhausted Tx with LEN and BORT. Clinical trial information: NCT01311687.
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Horie, Jun, Koichiro Takahashi, Shuuichi Shiranita, Kunihiko Anami und Shinichiro Hayashi. „Validation of Clinical Characteristics and Effectiveness of Pulmonary Rehabilitation in a COPD Population with Discrepancy between Exercise Tolerance and FEV1“. Healthcare 9, Nr. 1 (06.01.2021): 53. http://dx.doi.org/10.3390/healthcare9010053.
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This study’s objective was to examine the characteristics of patients with chronic obstructive pulmonary disease (COPD) presenting with various exercise tolerance levels. A total of 235 patients with stable COPD were classified into 4 groups: (1) LoFlo + HiEx—patients with a six-minute walking distance (6MWD) ≥350 m and percentage of predicted forced expiratory volume in 1 s (%FEV1.0) <50%; (2) HiFlo + HiEx—patients with a 6MWD ≥350 m and a %FEV1.0 ≥50%; (3) LoFlo + LoEx—patients with a 6MWD < 350 m and %FEV1.0 < 50%; and (4) HiFlo + LoEx—patients with a 6MWD <350 m and %FEV1.0 ≥ 50%. Aspects of physical ability in the HiFlo + LoEx group were significantly lower than those in the HiFlo + HiEx group. The HiFlo + LoEx group was characterized by a history of hospitalization for respiratory illness within the past year, treatment with at-home oxygen therapy, and lacking daily exercise habits. Following three months of pulmonary rehabilitation, the LoFlo + HiEx group significantly improved in the modified Medical Research Council dyspnea score, maximum gait speed, and 6MWD, while the HiFlo + LoEx group significantly improved in the percentage of maximal expiratory pressure, maximum gait speed, 6MWD, incremental shuttle walking distance, and St. George’s Respiratory Questionnaire score. The HiFlo + LoEx group had the greatest effect of three-month pulmonary rehabilitation compared to other groups.
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Gueguen, Florent. „Loger tous les sans-abri ?“ Esprit Novmbr, Nr. 11 (2017): 29. http://dx.doi.org/10.3917/espri.1711.0029.
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Marsolais, Gilles. „Dis-moi où tu loges…“. L’Annuaire théâtral: Revue québécoise d’études théâtrales, Nr. 22 (1997): 13. http://dx.doi.org/10.7202/041327ar.
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Castro-Fernández, Belén, und Rubén C. Lois-González. „« Se loger dans le passé »“. Espaces et sociétés 126, Nr. 3 (2006): 159. http://dx.doi.org/10.3917/esp.126.0159.
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Grelley, Pierre. „... en contrepoint - Loger les ouvriers“. Informations sociales 123, Nr. 3 (2005): 101. http://dx.doi.org/10.3917/inso.123.0101.
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Nishiguchi, Michele K. „Temperature Affects Species Distribution in Symbiotic Populations of Vibrio spp“. Applied and Environmental Microbiology 66, Nr. 8 (01.08.2000): 3550–55. http://dx.doi.org/10.1128/aem.66.8.3550-3555.2000.
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ABSTRACT The genus Sepiola (Cephalopoda: Sepiolidae) contains 10 known species that occur in the Mediterranean Sea today. AllSepiola species have a light organ that contains at least one of two species of luminous bacteria, Vibrio fischeriand Vibrio logei. The two Vibrio species coexist in at least four Sepiola species (S. affinis, S. intermedia, S. ligulata, andS. robusta), and their concentrations in the light organ depend on changes in certain abiotic factors, including temperature. Strains of V. fischeri grew faster in vitro and inSepiola juveniles when they were incubated at 26°C. In contrast, strains of V. logei grew faster at 18°C in culture and in Sepiola juveniles. When aposymbioticS. affinis or S. ligulata juveniles were inoculated with one Vibrio species, all strains of V. fischeri and V. logei were capable of infecting both squid species at the optimum growth temperatures, regardless of the squid host from which the bacteria were initially isolated. However, when two different strains of V. fischeri and V. logei were placed in direct competition with each other at either 18 or 26°C, strains of V. fischeri were present in sepiolid light organs in greater concentrations at 26°C, whereas strains of V. logei were present in greater concentrations at 18°C. In addition to the competition experiments, the ratios of the two bacterial species in adult Sepiola specimens caught throughout the season at various depths differed, and these differences were correlated with the temperature in the surrounding environment. My findings contribute additional data concerning the ecological and environmental factors that affect host-symbiont recognition and may provide insight into the evolution of animal-bacterium specificity.
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L�ger, Claude. „�loge de la taupe“. Sigila N�30, Nr. 2 (2012): 71. http://dx.doi.org/10.3917/sigila.030.0071.
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