Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis.

BACKGROUND: Interleukin-1 is pivotal in the pathogenesis of systemic juvenile idiopathic arthritis (JIA). We assessed the efficacy and safety of canakinumab, a selective, fully human, anti-interleukin-1β monoclonal antibody, in two trials. METHODS: In trial 1, we randomly assigned patients, 2 to 19 years of age, with systemic JIA and active systemic features (fever; ≥2 active joints; C-reactive protein, >30 mg per liter; and glucocorticoid dose, ≤1.0 mg per kilogram of body weight per day), in a double-blind fashion, to a single subcutaneous dose of canakinumab (4 mg per kilogram) or placebo. The primary outcome, termed adapted JIA ACR 30 response, was defined as improvement of 30% or more in at least three of the six core criteria for JIA, worsening of more than 30% in no more than one of the criteria, and resolution of fever. In trial 2, after 32 weeks of open-label treatment with canakinumab, patients who had a response and underwent glucocorticoid tapering were randomly assigned to continued treatment with canakinumab or to placebo. The primary outcome was time to flare of systemic JIA. RESULTS: At day 15 in trial 1, more patients in the canakinumab group had an adapted JIA ACR 30 response (36 of 43 [84%], vs. 4 of 41 [10%] in the placebo group; P<0.001). In trial 2, among the 100 patients (of 177 in the open-label phase) who underwent randomization in the withdrawal phase, the risk of flare was lower among patients who continued to receive canakinumab than among those who were switched to placebo (74% of patients in the canakinumab group had no flare, vs. 25% in the placebo group, according to Kaplan-Meier estimates; hazard ratio, 0.36; P=0.003). The average glucocorticoid dose was reduced from 0.34 to 0.05 mg per kilogram per day, and glucocorticoids were discontinued in 42 of 128 patients (33%). The macrophage activation syndrome occurred in 7 patients; infections were more frequent with canakinumab than with placebo. CONCLUSIONS: These two phase 3 studies show the efficacy of canakinumab in systemic JIA with active systemic features. (Funded by Novartis Pharma; ClinicalTrials.gov numbers, NCT00889863 and NCT00886769.).

Molecular genetic framework for protophloem formation.

The phloem performs essential systemic functions in tracheophytes, yet little is known about its molecular genetic specification. Here we show that application of the peptide ligand CLAVATA3/EMBRYO SURROUNDING REGION 45 (CLE45) specifically inhibits specification of protophloem in Arabidopsis roots by locking the sieve element precursor cell in its preceding developmental state. CLE45 treatment, as well as viable transgenic expression of a weak CLE45(G6T) variant, interferes not only with commitment to sieve element fate but also with the formative sieve element precursor cell division that creates protophloem and metaphloem cell files. However, the absence of this division appears to be a secondary effect of discontinuous sieve element files and subsequent systemically reduced auxin signaling in the root meristem. In the absence of the formative sieve element precursor cell division, metaphloem identity is seemingly adopted by the normally procambial cell file instead, pointing to possibly independent positional cues for metaphloem formation. The protophloem formation and differentiation defects in brevis radix (brx) and octopus (ops) mutants are similar to those observed in transgenic seedlings with increased CLE45 activity and can be rescued by loss of function of a putative CLE45 receptor, BARELY ANY MERISTEM 3 (BAM3). Conversely, a dominant gain-of-function ops allele or mild OPS dosage increase suppresses brx defects and confers CLE45 resistance. Thus, our data suggest that delicate quantitative interplay between the opposing activities of BAM3-mediated CLE45 signals and OPS-dependent signals determines cellular commitment to protophloem sieve element fate, with OPS acting as a positive, quantitative master regulator of phloem fate.

Propagação de orquídea Gongora quinquenervis por semeadura in vitro

O objetivo deste trabalho foi avaliar a germinação e a organogênese in vitro em Gongora quinquenervis em dois meios nutritivos, Knudson "C" e Murashige & Skoog, com três concentrações de BAP (0,0, 0,5 e 1,0 mg L-1). Os protocormos cultivados no meio Knudson "C" necrosaram. A maioria dos embriões cultivados em meio Murashige & Skoog tendeu a diferenciar-se em calos. Estes calos apresentaram alto potencial morfogenético, regenerando grande número de plantas via organogênese indireta, sobretudo no material proveniente do tratamento desprovido de BAP. Foram formadas 41 plantas pela rota normal de germinação, contrastando com 715 plantas regeneradas via organogênese indireta.

Abatacept improves health-related quality of life, pain, sleep quality, and daily participation in subjects with juvenile idiopathic arthritis.

OBJECTIVE: To assess health-related quality of life (HRQOL) in abatacept-treated children/adolescents with juvenile idiopathic arthritis (JIA). METHODS: In this phase III, double-blind, placebo-controlled trial, subjects with active polyarticular course JIA and an inadequate response/intolerance to ≥1 disease-modifying antirheumatic drug (including biologics) received abatacept 10 mg/kg plus methotrexate (MTX) during the 4-month open-label period (period A). Subjects achieving the American College of Rheumatology Pediatric 30 criteria for improvement (defined "responders") were randomized to abatacept or placebo (plus MTX) in the 6-month double-blind withdrawal period (period B). HRQOL assessments included 15 Child Health Questionnaire (CHQ) health concepts plus the physical (PhS) and psychosocial summary scores (PsS), pain (100-mm visual analog scale), the Children's Sleep Habits Questionnaire, and a daily activity participation questionnaire. RESULTS: A total of 190 subjects from period A and 122 from period B were eligible for analysis. In period A, there were substantial improvements across all of the CHQ domains (greatest improvement was in pain/discomfort) and the PhS (8.3 units) and PsS (4.3 units) with abatacept. At the end of period B, abatacept-treated subjects had greater improvements versus placebo in all domains (except behavior) and both summary scores. Similar improvement patterns were seen with pain and sleep. For participation in daily activities, an additional 2.6 school days/month and 2.3 parents' usual activity days/month were gained in period A responders with abatacept, and further gains were made in period B (1.9 versus 0.9 [P = 0.033] and 0.2 versus -1.3 [P = 0.109] school days/month and parents' usual activity days/month, respectively, in abatacept- versus placebo-treated subjects). CONCLUSION: Improvements in HRQOL were observed with abatacept, providing real-life tangible benefits to children with JIA and their parents/caregivers.

Cronograma de amostragem de alface cultivada em hidroponia para ajuste de curvas de crescimento vegetativo

O objetivo deste trabalho foi determinar o cronograma de amostragem de plantas de alface hidropônica, para ajuste de curvas de crescimento durante o período vegetativo. Foram realizados dois cultivos de alface, variedade Regina, de 8/9/2004 a 19/11/2004 (primavera/verão) e 22/2/2005 a 24/5/2005 (verão/outono), em estufas de plástico do Dep. de Fitotecnia, da UFSM, Santa Maria, RS. A partir do ajuste do modelo co-seno com amostragem diária, registrada como padrão, diferentes intervalos entre as amostragens foram simulados para o ajuste do mesmo modelo. A fim de se encontrar o intervalo adequado, foi comparada a variância de falta de ajuste do modelo de amostragem diária com as variâncias de falta de ajuste dos modelos com diferentes intervalos de amostragens pelo teste F. Os cronogramas de amostragens para ajuste de curvas de crescimento de plantas de alface sob hidroponia, para experimentos de primavera/verão e verão/outono, possuem intervalos iguais a dois dias, para fitomassa seca total da planta e da folha; intervalos de quatro dias, para fitomassa de raiz; e, diariamente, para área foliar.

[Assise. Basilica di San Francesco, basilica superiore]

Référence bibliographique : Weigert, 20

Pontificale parisiense [Pontifical dit de Poitiers ou de Vierzon].

Sur le feuillet de garde A, cette note autographe de Mabillon : « Hic codex optimae notae scriptus est ante annos circiter octingentos. Multa scitu digna continet, maxime in triduo ante Pascha. In litaniis sabbati sancti fit supplicatio pro congregatione S. Petri, quem patronum habet Pictavensis ecclesia. Invocantur etiam in iisdem sanctus Hilarius et sancta Radegundis, qui praecipue ad ecclesiam Pictavensem pertinent ; sed nulla mentio de aliis sanctis ejusdem dioecesis. Haec scripsi XI kal. decembris an. 1695. — F. J. M. » Fol. 1 : « Benedictio episcoporum. — Consecratio ». Fol. 2 : « Oratio ad ordinandum praesbiterum. — Consecratio. ». Fol. 3 : « Oratio ad ordinandum diaconum. — Consecratio. » Fol. 4 : « Ordo qualiter in Romana ecclesia praesbiteri, diaconi, subdiaconi ordinandi sunt. » Fol. 5 : « Ordinatio subdiaconi ». Fol. 5v° : « Ordinatio ostiarii. » Fol. 6 : « Ordinatio lectoris ». Fol. 6v° : « Ordinatio exorcistae ». Fol. 7 : « Ordinatio acoliti ». Fol. 7v° : « Incipit ordo qualiter publice vel specialiter agitur modus paenitentiae secundum censuram ecclesiasticam, quod quarta feria quinquagesime inchoatur ». Fol. 8v° : « Confessio pura coram Deo et angelis et coram omnibus sanctis » : — de superbia (fol. 12) ; de inani gloria (fol. 13) ; de invidia (fol. 13 vo) ; de ira (fol. 14 vo) ; de tristitia (fol. 15) ; de avaricia (fol. 16) ; de ventris ingluvie (fol. 20) ; de luxuria (fol. 23). Fol. 40v° : « Missa pro paenitentibus et confitentibus, sive unus sive plures fuerint ». Fol. 43 : « Denunciatio scrutinii quod tertia ebdomada in quadragesima secunda feria iniciatur ». Fol. 43v° : « Oratio super electos ad catecuminum faciendum ». Fol. 44 : « Benedictio salis dandi caticuminis. » — Prières et exhortations aux catéchumènes. Explication des évangiles. Fol. 54-56 : Le Credo, en grec avec traduction latine au-dessus. La traduction est faite de mot à mot. Pour l'article grec, le traducteur s'est contenté de mettre au-dessus, dans le texte latin, ces lettres ar. (articulus). Fol. 58v° : Explication du Pater. Fol. 60v° : « Incipit missa primi scrutinii ». Fol. : 63 : « Alia missa de secundo scrutinio ». Fol. 66v° : « Missa de tertio scrutinio ». Fol. 70 : « Sabbato ante diem Palmarum ». Fol. 72 : « Dominica indulgentiae quae est dies Palmarum ». Fol. 73 : Les 36 premiers vers de la pièce Gloria, laus de Théodulfe, évêque d'Orléans (Henry Martin signale l'éd. qu'en a fait Duemmler dans les Poetae latini aevi carolini, t. I, p. 558 : « Gloria, laus et honor tibi sit, Christe redemptor, Cui puerile decus promsit osanna pium. Israhel es tu rex Davidis et inclita proles, Nomine qui in Domini, rex benedicte, venis... » Fol. 95 :« Feria II post Palmas ». Fol. 98v° : « Feria tertia ». Fol. 130 : « Feria V, quae est cena Domini ». Fol. 141v° : « Alia missa eodem die, si plures ad reconciliandum venerint ». Fol. 154 : « Missa chrismalis ». Fol. 160 : Litanies. A noter : SS. Denys, Quentin, Julien, Géréon, Hilaire, Martin, Aignan, Benoît, Cloud [Clodoald], Ste Geneviève. Fol. 170v° : « Benedictio chrismatis principalis ». Fol. 171 : « Exorcismus olei ad baptizandos ». Fol. 173v° : In cena Domini de Flavius, évêque: « Versus Flavii episcopi ad mandatum in cena Domini ». « Tellus a cethra jubilent in magni cena principis, Que protoplasti pectora vite purgavit ferculo ; Hac nocte factor omnium potenti sat mysterio Carnem suam cum sanguine in escam transfert anime. — Tellus. » Fol. 174 : « Item versus Bedae » (Bède). « Fuit Domini dilectus languens a Bethania Lazarus beatus sacris olim cum sororibus quas Jhesus eternus Amor diligebat plurimum Martham simul et Mariam, felices per secula. » Fol. 174v° : « Feria VI quae est Parasceve ». Fol. 192v° : « Pange lingua gloriosi Proelium certaminis ». Fol. 193 : « Incipit de sabbato sancto. — Ordo baptisterii ». Fol. 200v° : Litanies. A noter : SS. Quentin, Cucuphat, Julien, Lucien, Hilaire, Martin, Benoît, Germain, Columban, Samson ; SStes Geneviève, Brigitte, Colombe, Radegonde, Aldegonde. — A noter aussi (fol. 201 vo) : « Ut exercitum Francorum conservare digneris. — Ut illum abbatem et cunctam congregationem sancti illius in tuo apto servitio conservare digneris... » Fol. 202 : « Benedictio cerei. — Exultet jam angelica turba coelorum. Exultent divina mysteria... », avec neumes. Fol. 208 : Litanies. A noter : SS. Hilaire, Martin, Ambroise, Maur, Maurille, Lezin, évêque d'Angers ; SStes Blandine, Nathalie. Fol. 210 : « Inde canitur hic versus : »« Urbs beata Hierusalem, dicta pacis visio, que construitur in celis vivis ex lapidibus... » Fol. 210v° : « Benedictio fontis ». Fol. 213 : vers « Tibi laus perennis auctor baptismatis... » Fol. 213v° : Litanies. A noter : SS. Martin, Brice, Médard, Vaast, Germain, Marcel, Hilaire ; SStes Reine, Julienne, Gertrude, Colombe, Geneviève, Afre, Radegonde, Aldegonde, Darie, Brigitte, Paule. — A noter (fol. 215) : « Ut exercitum Francorum conservare digneris. — Ut congregationem sancti Petri in tuo apto servitio conservare digneris ». Fol. 223 : « Finit ordo baptisterii ». Fol. 227 : Le jour de Pâques. Fol. 230v° : « Feria II ». Fol. 241 : « Feria quinta ». Fol. 245v° : « Feria VI ». Fol. 248 : « Sabbato ». Fol. 252v° : « In octavis Paschae ». Fol. 256v° : « Missa in octavis Paschae pro baptizatis ». Fol. 257v° : « Missa pro parroechias in diebus paschalibus... ». Fol. 258v° : « Fides catholica continens credulitatem... » Fol. 269 : « Missa pro conjugibus sterilitate infecundis in procreatione prolis ». Fol. 273v° : « Orationes ad benedicendam aquam aspergendam in domo. — Exorcismus salis ». Fol. 274 : « Benedictio salis. — Exorcismus aque. — Benedictio aque ». Fol. 274v° : « Benedictio salis et aquae... » etc. Fol. 275 : « Exorcismus salis et aquae contra fulgura ». Fol. 276 : « Benedictio salis ad pecora. — Orationes ad clericum faciendum ». Fol. 276v° : « Benedictio putei ». Fol. 277 : « Benedictio frugum novarum ». Fol. 277v° : « Benedictio panis. — Oratio ad capillarum (sic). — Alia ad tonsorandum puerum ». Fol. 278 : « Oratio post tonsionem. — Oratio ad barbas tondendas ». Fol. 278 : « lncipit actio pontificalis ad... » . Le verso du feuillet 279 est tout à fait effacé. Neumes français, du IXe s., aux f. 202-204 (l'Exultet) ; addition du Xe s. au f. 203 v° (Bernard).

An international registry on autoinflammatory diseases: the Eurofever experience.

OBJECTIVE: To report on the demographic data from the first 18 months of enrollment to an international registry on autoinflammatory diseases in the context of the Eurofever project. METHODS: A web-based registry collecting baseline and clinical information on autoinflammatory diseases and related conditions is available in the member area of the PRINTO web-site. Anonymised data were collected with standardised forms. RESULTS: 1880 (M:F=916:964) individuals from 67 centers in 31 countries have been entered in the Eurofever registry. Most of the patients (1388; 74%), reside in western Europe, 294 (16%) in the eastern and southern Mediterranean region (Turkey, Israel, North Africa), 106 (6%) in eastern Europe, 54 in Asia, 27 in South America and 11 in Australia. In total 1049 patients with a clinical diagnosis of a monogenic autoinflammatory diseases have been enrolled; genetic analysis was performed in 993 patients (95%): 703 patients have genetically confirmed disease and 197 patients are heterozygous carriers of mutations in genes that are mutated in patients with recessively inherited autoinflammatory diseases. The median diagnosis delay was 7.3 years (range 0.3-76), with a clear reduction in patients born after the identification of the first gene associated with autoinflammatory diseases in 1997. CONCLUSIONS: A shared online registry for patients with autoinflammatory diseases is available and enrollment is ongoing. Currently, there are data available for analysis on clinical presentation, disease course, and response to treatment, and to perform large scale comparative studies between different conditions.

Eficácia de uma nova formulação de glifosato para o controle de grama-seda (Cynodon dactylon), em pomar de citros.

Avaliou-se a eficácia do herbicida glifosato potássico, comparado ao sulfosato e ao glifosato amínico, utilizados como padrões comerciais. Os herbicidas foram aplicados em um pomar de laranja da variedade Pêra-rio, infestado por grama-seda (Cynodon dactylon) com aproximadamente 25 cm de altura, em 70% da área. O experimento foi instalado no município de Taiúva-SP, em solo Podzólico Vermelho-Amarelo, distrófico, de textura arenosa, com relevo suave ondulado. Os tratamentos testados foram: glifosato potássico (ZAPP Qi) a 1,05; 2,10 e 2,50 kg e.a./ha, sulfosato (ZAPP) e glifosato amínico (ROUNDUP CS) a 1,98 e 2,16 kg e.a./ha, respectivamente, além da testemunha sem capina. Os herbicidas foram aplicados em pós-emergência da planta daninha, com pulverizador costal, à pressão constante (mantida por CO2 comprimido) de 2,5 kg/cm², munido de barra com seis bicos de jato plano ("leque") DG 11002, com um consumo de calda equivalente a 200 L/ha. Os melhores resultados de controle foram obtidos com 2,5 kg e.a./ha do glifosato potássico, que também garantiu menor brotação da grama-seda. No entanto, a dosagem de 2,10 kg e.a./ha deste mesmo herbicida não foi menos eficaz que o sulfosato e o glifosato, com 1,98 e 2,16 kg e.a./ha, respectivamente.

Precision of the Retinal Tomograph as a Screening Device.

Purpose: To assess the diagnostic accuracy of the Heidelberg Retinal Tomograph 3 (HRT3) as a screening device in comparison with the reference standard of Octopus standard automated perimetry results (SAP) combined with clinical findings. Methods: All patients underwent screening examinations and investigations within a single day. Abnormal screening results were classified as follows: The HRT3: Either "borderline" or "outside normal limits" using the global Moorfields classification (MFC); SAP and clinical exam: A mean defect > 2.4 dB or "outside normal limits" clear text analysis of SAP; and one of the following i) IOP > 21 mmHg, ii) Van Herrick < ¼, iii) cup disc ratio > 0.55, iv) optic nerve head abnormality, v) narrow iridocorneal angle or vi) evidence of peripheral anterior synechiae on gonioscopy. Results: The mean age of the participants was 59.9 years (± 14.8 [21, 91]). Twenty-three subjects (16 %) were classified as abnormal on SAP and clinical exam. The HRT3 classification had a sensitivity of 30 % (95 % CI [16 %, 51 %]) with associated specificity of 58 % (95 % CI [49 %, 66 %]). Of the sixty subjects classified as borderline or outside normal limits with the HRT MFC global result, seven subjects were also abnormal according to SAP and clinical exam. Conclusion: The results suggest that the HRT3 may not be suitable as a sole screening device; however, further investigation is necessary.

Primary root protophloem differentiation requires balanced phosphatidylinositol-4,5-biphosphate levels and systemically affects root branching.

Protophloem is a specialized vascular tissue in growing plant organs, such as root meristems. In Arabidopsis mutants with impaired primary root protophloem differentiation, brevis radix (brx) and octopus (ops), meristematic activity and consequently overall root growth are strongly reduced. Second site mutation in the protophloem-specific presumed phosphoinositide 5-phosphatase COTYLEDON VASCULAR PATTERN 2 (CVP2), but not in its homolog CVP2-LIKE 1 (CVL1), partially rescues brx defects. Consistent with this finding, CVP2 hyperactivity in a wild-type background recreates a brx phenotype. Paradoxically, however, while cvp2 or cvl1 single mutants display no apparent root defects, the root phenotype of cvp2 cvl1 double mutants is similar to brx or ops, although, as expected, cvp2 cvl1 seedlings contain more phosphatidylinositol-4,5-biphosphate. Thus, tightly balanced phosphatidylinositol-4,5-biphosphate levels appear essential for proper protophloem differentiation. Genetically, OPS acts downstream of phosphatidylinositol-4,5-biphosphate levels, as cvp2 mutation cannot rescue ops defects, whereas increased OPS dose rescues cvp2 cvl1 defects. Finally, all three mutants display higher density and accelerated emergence of lateral roots, which correlates with increased auxin response in the root differentiation zone. This phenotype is also created by application of peptides that suppress protophloem differentiation, CLAVATA3/EMBRYO SURROUNDING REGION 26 (CLE26) and CLE45. Thus, local changes in the primary root protophloem systemically shape overall root system architecture.