ライフサイエンスコーパス: dose-escalation

1 lly affecting this planning (e.g., regarding dose escalation).

2 ere screened during the safety windows after dose escalation).

3 0 and topotecan in 3-week cycles using 3 + 3 dose escalation.

4 ch in targeting agents and radiation therapy dose escalation.

5 lled, and 22 were eligible and evaluable for dose escalation.

6 which could be restored with further Notch1 dose escalation.

7 o drug solubilization, biocompatibility, and dose escalation.

8 allowing a 2-week observation period before dose escalation.

9 ients (91%) achieved TCs of 3-7 mug/mL after dose escalation.

10 he target volumes for potential radiotherapy dose escalation.

11 onse to traditional diuretic therapy despite dose escalation.

12 olume would facilitate isotoxic radiotherapy dose escalation.

13 egression model with overdose control-guided dose escalation.

14 n either group required opioid initiation or dose escalation.

15 without evidence of increased sedation with dose escalation.

16 eria that was not previously observed during dose escalation.

17 nd OIH counteract opioid analgesia and drive dose escalation.

18 tested durvalumab doublets in parallel 3 + 3 dose escalations.

19 parental reports, daily symptom diaries, and dose escalations.

20 In phase 1 (dose escalation), 13 patients received obinutuzumab 400

21 gioedema were reported for protocols with <6 doses escalation (2.6% [1.1%-4.1%] versus 2.6% [1.9%-3.2

22 In a standard 3 + 3 phase 1 design for dose escalation, (212)Pb-TCMC-trastuzumab was delivered

23 Dose escalation (3 + 3 design) in all solid tumors was f

24 eviously treated AL were enrolled, 15 during dose escalation (6 at 2 mg, 3 at 3 mg, and 6 at 4 mg) an

25 enty-seven patients were enrolled: 11 during dose escalation (6 at 4.0 mg and 5 at 5.5 mg) and 16 dur

26 at each occurred over an 8-week time period; dose escalation (8 RMs; targeted doses of 5.0E+03, 5.0E+

27 tion of CD patients in remission than before dose escalation (88% vs 65%; P = .020) and a decrease in

28 tially at trial entry according to the 3 + 3 dose-escalation algorithm and depending on the number of

29 rapy was more costly but more effective than dose-escalation allopurinol therapy, with an incremental

30 Dose-escalation allopurinol-febuxostat sequential therap

31 Dose-escalation allopurinol-febuxostat sequential therap

32 th switching to nilotinib than with imatinib dose escalation, although the difference was not statist

33 and IL-4 production) were suppressed during dose escalation and after 6 months of maintenance dosing

34 RIPF remains a major limiting factor to dose escalation and an obstacle to applying more promisi

35 PPI dose escalation and continued chronic therapy in those u

36 in the mesolimbic pathway may promote opioid dose escalation and contribute to opioid abuse-associate

37 Phase 1 study with dose escalation and dose expansion at the University of

38 id a phase 1/2, open-label, non-comparative, dose escalation and expansion trial (CheckMate 040) of n

39 Results In the dose-escalation and -expansion cohorts, 33 and 18 patien

40 The study was done in two parts, with dose-escalation and dose-expansion phases.

41 In this phase 1, first-in-human dose-escalation and dose-expansion study, eligible patie

42 eived anti-interleukin-1alpha monotherapy in dose-escalation and expansion groups.

43 Results The dose-escalation and expansion phases enrolled 26 and 25

44 relapsed or refractory AML, from the phase 1 dose-escalation and expansion phases of the study.

45 with ARDS in an open-label study (comprising dose-escalation and expansion phases).

46 at the recommended dose of 750 mg/day in the dose-escalation and expansion phases.

47 This first-in-human, dose-escalation and expansion study evaluated the safety

48 city at target doses from 200 to 1,200 mg in dose-escalation and safety expansion cohorts.

49 We did an open-label, dose-escalation, and phase 1 study of MABp1 in adults wi

50 Dose escalation ceased at 160 mg per day given lack of M

51 the publication of a first-in-man phase I/II dose escalation clinical trial in patients with radiatio

52 two of three patients enrolled in the 450 mg dose-escalation cohort had two dose-limiting toxicities

53 L was started due to lack of activity in the dose-escalation cohort).

54 2012, we enrolled 95 patients (34 to the NHL dose-escalation cohort, 18 to the CLL dose-escalation co

55 he NHL dose-escalation cohort, 18 to the CLL dose-escalation cohort, 34 with NHL to the expansion coh

56 syndrome occurred in 3 of 56 patients in the dose-escalation cohort, with one death.

57 o dose-limiting toxicities were noted in the dose-escalation cohort; on the basis of pharmacokinetic,

58 In this phase I, open-label, dose-escalation, cohort-expansion study, patients with r

59 in Germany; 27 patients were enrolled in the dose-escalation cohorts (0.125-1.75 mg/kg) and 31 patien

60 otal of 66 patients were enrolled (54 in the dose-escalation cohorts and 12 in the safety expansion).

61 ax was given at 300, 600, 900, or 1200 mg in dose-escalation cohorts and 1200 mg in the safety expans

62 eek dose ramp-up period for most patients in dose-escalation cohorts and for all patients in safety e

63 in (0.1-2.4 mg/kg every 21 days) in separate dose-escalation cohorts for NHL and CLL.

64 th myelodysplastic syndrome in the daily x 5 dose-escalation cohorts, 28 patients with acute myeloid

65 myelodysplastic syndrome in the once-weekly dose-escalation cohorts, and 11 patients with acute myel

66 myelodysplastic syndrome in the twice-weekly dose-escalation cohorts.

67 ecitabine doses of 3-125 mg/m(2) in separate dose-escalation cohorts.

68 Sixty-six patients were enrolled (30, dose-escalation cohorts; 36, safety expansion).

69 Furthermore, the feasibility of triazole dose escalation, combination therapy, and prophylaxis we

70 ven patients were enrolled in seven cohorts (dose-escalation component).

71 tive site occurred at 2.5 mg/kg per day, and dose escalation continued to 12.5 mg/kg per day without

72 g part 1, patients received eltrombopag, and dose-escalation criteria for part 2 were determined.

73 Finally, in vitro dose-escalation cytotoxicity assays confirm the biocompa

74 After a 2-week lead-in with weekly dose escalation, daily venetoclax was given at 300, 600,

75 Methods In a 3 + 3 dose-escalation design (n = 25), patients received a sin

76 was orally administered in a standard 3 + 3 dose-escalation design at four different dosing schedule

77 ls by use of a bivariate Bayesian sequential dose-escalation design to assess safety and efficacy.

78 elapsed or RRMM patients into an open-label, dose-escalation design to determine the maximum tolerate

79 se 1, patients were assigned following a 3+3 dose-escalation design to one of four cohorts to receive

80 A 3 + 3 dose-escalation design was used in which we treated pati

81 A 3 + 3 dose-escalation design was used in which we treated pati

82 ses of 100 to 1,800 mg, according to a 3 + 3 dose-escalation design, followed by an expansion phase a

83 using an open-label, single-ascending 3 + 3 dose-escalation design.

84 once per day in 28-day cycles using a 3 + 3 dose-escalation design.

85 d generalizability of model-guided, adaptive dose-escalation designs, and it provides an approach for

86 Radiotherapy dose escalation did not improve chemoradiotherapy outcom

87 ing for tumor delineation, dose painting for dose escalation, dose adaptation throughout treatment, a

88 Part 1 (dose escalation) evaluated 4 daratumumab doses plus lena

89 We report interim data from a phase I/II dose-escalation/expansion study of NEOD001 in patients w

90 induced diabetic rabbit ear ulcer model in a dose escalation fashion.

91 tion (slow escalation; n = 70), 40-mg 2-week dose escalation (fast escalation, n = 70), oral placebo

92 Phase 1/2a, multicenter, open-label, dose-escalation, fellow-eye-controlled study.

93 In this phase 1, dose-escalation, first-in-man trial, we recruited patien

94 ficacy of switching to nilotinib vs imatinib dose escalation for patients with suboptimal cytogenetic

95 Nine children received insulin with dose escalations from 2.5 to 7.5 mg (n = 3), 2.5 to 22.5

96 immunosuppression (if possible): ganciclovir dose escalation, ganciclovir and foscarnet combination,

97 During dose escalation, grade 2 dose-limiting toxic effects occ

98 5, 32 patients received veliparib (22 in the dose-escalation group; ten in the safety expansion group

99 daily, or equivalent placebo with mandatory dose escalation if no serious adverse effects were exper

100 However, scarce evidence addresses whether dose escalation improves overall survival.

101 ich may have implications in clinical opioid dose escalation in chronic pain management.

102 ing, and understanding such designs to guide dose escalation in phase I trials.

103 These results provide a rationale for dose escalation in T-cell-directed immunotherapy and rev

104 safety events were observed despite a 4-fold dose escalation in the study.

105 This study evaluated the effects of RT dose escalation in the treatment of IHCC.

106 mputer program, clinicians can conduct 3 + 3 dose escalations in practice with virtually no logistic

107 Dose-limiting toxicities observed during dose escalation included grade 3 increased alanine amino

108 Here we report that dose escalation is imperative for safe, subcutaneous del

109 of allopurinol daily, 0.39 success rate) and dose escalation (</=120 mg of febuxostat daily, 0.82 suc

110 Although this dose-escalation model limited the rates of clinically si

111 oral gilteritinib once daily in one of seven dose-escalation (n=23) or dose-expansion (n=229) cohorts

112 During dose escalation, nivolumab showed a manageable safety pr

113 Dose escalation occurred over 5 dose levels.

114 Dose escalation of a folate-targeted vinblastine compoun

115 Dose escalation of alisertib followed the rolling six de

116 To determine whether dose escalation of carmustine in combination with dual-d

117 on in antiplatelet therapy defined as either dose escalation of clopidogrel or replacement of clopido

118 Dose escalation of rifampicin achieves >90% Wolbachia de

119 Our trial was designed to determine whether dose escalation of the radiation boost or two cycles of

120 Conclusion Dose escalation of varlilumab to 10 mg/kg was well toler

121 t common choice among clinicians for phase I dose-escalation oncology trials.

122 VRC 311 was a phase 1, dose-escalation, open-label clinical trial of a virus-li

123 We conducted a phase 1, dose-escalation, open-label trial of cAd3-EBO.

124 In this dose-escalation, open-label, phase 1 study, we recruited

125 alternative strategies such as radiotherapy dose escalation or surgery.

126 Patients were enrolled into one of seven dose-escalation or dose-expansion cohorts assigned to re

127 We assigned patients to dose-escalation or expansion cohorts, ranging from 0.05

128 ch 10 peanut-allergic adults received weekly dose escalations over 10 weeks from 10 mcg to 3063 mcg,

129 Patient recruitment to the dose-escalation part reported here is closed.

130 g toxicity, and all patients enrolled in the dose-escalation part were assessed for the secondary end

131 1.1-21.4); 43 patients were included in the dose escalation phase (A1), 25 patients in part A2, and

132 In the dose escalation phase (n = 31), duvelisib 8 to 100 mg tw

133 Here we report the results of a first-in-man dose escalation phase 1 clinical trial of 3BNC117, a pot

134 We first performed a dose escalation phase 1 study to determine the recommend

135 andomized, double-blind, placebo-controlled, dose escalation phase 1 study.

136 A 3+3 dose-escalation phase (15 patients) was followed by an e

137 nivolumab 0.1-10 mg/kg every 2 weeks in the dose-escalation phase (3+3 design).

138 ients who received 500 mg twice a day in the dose-escalation phase (grade 3 acne [n=1] and intolerabl

139 In the dose-escalation phase (n = 47), panobinostat was adminis

140 In the dose-escalation phase (part 1), patients with diffuse la

141 In the initial dose-escalation phase 1 stage of the trial, patients rec

142 domized, double-blinded, placebo-controlled, dose-escalation phase 1 study.

143 This was an open-label, dose-escalation phase 1 trial done at two study sites in

144 In this single-centre, open-label, dose-escalation phase 1 trial, we recruited adult patien

145 We performed three open-label, dose-escalation phase 1 trials and one randomized, doubl

146 In this open-label, dose-escalation phase 1-2a study, we gave monthly intrat

147 in patients with advanced solid tumours in a dose-escalation phase 1a trial.

148 months ranging from 0.03 to 20 mg/kg in the dose-escalation phase and 10 to 30 mg/kg in the dose-exp

149 (Dec 12, 2016), three (10%) patients in the dose-escalation phase and 20 (53%) in the dose-expansion

150 le patients were treated (48 patients in the dose-escalation phase and 214 in the dose-expansion phas

151 Fifty-seven patients were treated in the dose-escalation phase and 26 in the dose-expansion phase

152 SCLC were enrolled into the study, 29 to the dose-escalation phase and 38 to the dose-expansion phase

153 es of 7 or less (Child-Pugh A or B7) for the dose-escalation phase and 6 or less (Child-Pugh A) for t

154 mg, 1350 mg, or 2000 mg every 2 weeks in the dose-escalation phase and at the optimal biological dose

155 1, 2015, 102 patients were enrolled into the dose-escalation phase and received treatment.

156 30 (63%) of 48 patients in the dose-escalation phase died (not determined to be related

157 In the dose-escalation phase of our study, patients received ve

158 A dose-escalation phase to determine the MTD of R-INO was

159 A dose-escalation phase was conducted at seven hospitals o

160 A 3+3 dose-escalation phase was followed by 2 expansion cohort

161 The primary endpoint of the dose-escalation phase was safety.

162 In the dose-escalation phase, 25 patients with heavily pretreat

163 In the dose-escalation phase, 56 patients received active treat

164 After the dose-escalation phase, a second dosing arm was started w

165 After the dose-escalation phase, an expansion cohort was treated a

166 In the dose-escalation phase, an MTD was not reached at doses r

167 During the cell dose-escalation phase, an objective complete response wa

168 cine and 12 to placebo) were enrolled in the dose-escalation phase, in which the 30 mug and 60 mug do

169 In the dose-escalation phase, patients received 3 to 80 mg/m(2)

170 In the dose-escalation phase, patients who had progressed after

171 In part 1, the dose-escalation phase, we administered daratumumab at do

172 nrolled; 42 received treatment in the formal dose-escalation phase.

173 t 21, 2013, 12 patients were enrolled in the dose-escalation phase.

174 n optimal tolerated dose (OTD) in the first, dose-escalation phase.

175 expansion phase and 15% (95% CI 6-28) in the dose-escalation phase.

176 at a dose of 100 to 400 mg once daily in the dose-escalation (phase 1) portion of the study and 100 m

177 (START) trial was a multicentre, open-label, dose-escalation, phase 1 clinical trial.

178 In this dose-escalation, phase 1 study we recruited patients fro

179 In this open-label, dose-escalation, phase 1 study, we recruited adult patie

180 We conducted an open-label, single-dose-escalation, phase 1 trial involving 15 patients wit

181 T study, a double-blind, placebo-controlled, dose-escalation, phase 1/2 clinical pilot study performe

182 The open-label, parallel-cohort, dose-escalation, phase I CheckMate 016 study evaluated t

183 onocenter, placebo-controlled, single-blind, dose-escalation pilot study, 18 subjects with perennial

184 lectinib (300-900 mg twice a day) during the dose-escalation portion of the study (phase 1), to ascer

185 e-limiting toxic effects occurred during the dose-escalation portion of the study.

186 In the phase 1 dose-escalation portion, the primary objectives were to

187 and Ad6-NSmut) encoding HCV NS proteins in a dose escalation, prime-boost regimen, with and without c

188 Dose escalation proceeded until either the maximum-toler

189 ith (166)Ho radioembolization according to a dose escalation protocol (20-80 Gy).

190 s placed and adenosine was given following a dose-escalation protocol until atrioventricular block wa

191 fraction were randomly assigned to a 6-week dose-escalation regimen of isosorbide mononitrate (from

192 utide (doses reached after following a fixed dose-escalation regimen) or once-daily insulin glargine

193 We did a phase 1, open-label, dose-escalation safety study comparing brentuximab vedot

194 After adjustments to the dose-escalation schedule, clinical tumor lysis syndrome

195 We applied a two-stage dose-escalation scheme (single patient and traditional 3

196 The phase 1 portion used a 3 + 3 dose-escalation scheme to determine the maximum tolerate

197 Further dose escalation should be conducted with care, as the hi

198 mice exhibited reactions during 5-6 weeks of dose escalation single PN and TN challenges.

199 (standard escalation; n = 71), 40-mg 8-week dose escalation (slow escalation; n = 70), 40-mg 2-week

200 -613 for the first cohort in the traditional dose-escalation stage was the same as that used in the l

201 The traditional 3+3 dose-escalation stage was triggered if toxic effects att

202 sed in the last cohort of the single-patient dose-escalation stage.

203 10 mg (n = 70), 20 mg (n = 70), 40-mg 4-week dose escalation (standard escalation; n = 71), 40-mg 8-w

204 Compound 1 was tested in dose escalation studies in rats and dogs and was found t

205 Dose escalation studies of (68)Ga-labeled 1,4,7-tris(car

206 Long term dose escalation studies showed that miR-30c mimic caused

207 In dose escalations studies in diabetic minipigs, a higher

208 n shown in short-term (1- to 2-week) phase 1 dose-escalation studies to correct neutropenia and other

209 s, we highly encourage its adoption in early dose-escalation studies whenever the 3 + 3 design is als

210 We conducted a phase I dose escalation study in which 9 patients with relapsed/

211 and intraperitoneal CEA-expressing tumors: a dose escalation study to determine the optimal MN-14 pro

212 A phase 1b, open-label, single-dose escalation study was conducted to evaluate safety,

213 In a phase 1 or 2 dose escalation study, RhD(+) patients (61 subjects) wit

214 ospective, open-label, multicenter phase 1/2 dose escalation study, we used a next-generation, mono-p

215 id this randomised, multicentre, open-label, dose-escalation study (1703) at 17 hospitals in the USA,

216 This first-in-human dose-escalation study assessed the maximum-tolerated dos

217 This phase 1b, open-label, dose-escalation study assessed the safety, efficacy, and

218 Phase 1, open-label, uncontrolled, dose-escalation study at 5 US retinal clinics between No

219 cebo-controlled, active-comparator, phase 1, dose-escalation study at one centre in Vienna, Austria.

220 In this open-label phase 1 dose-escalation study conducted at Baylor College of Med

221 This phase 1 dose-escalation study determined the maximum tolerated d

222 After an open-label dose-escalation study in a pilot safety cohort, we did a

223 ndomized, placebo-controlled, double-blinded dose-escalation study in an HIV-negative adult South Afr

224 d, single-blind, placebo-controlled, phase 1 dose-escalation study in healthy adult volunteers with s

225 eaction plates, 92 miRNAs were assessed in a dose-escalation study in healthy volunteers at 4 differe

226 In this exploratory, open-label, dose-escalation study in the UK, male and female patient

227 This phase 1/2 dose-escalation study investigated the combination of ca

228 ty and efficacy have been shown in a phase 1 dose-escalation study involving a unilateral subretinal

229 The dose-escalation study is the first part of a two-part st

230 We previously reported a phase 1b dose-escalation study of carfilzomib, lenalidomide, and

231 The clinical activity observed in a phase I dose-escalation study of concurrent therapy with nivolum

232 rall safety and preliminary activity in this dose-escalation study of CUDC-907 monotherapy in patient

233 We conducted a phase 1 dose-escalation study of daily oral venetoclax in patien

234 of leukemia relapse, we initiated a phase 1 dose-escalation study of membrane-bound interleukin 21 (

235 We performed a dose-escalation study of MVA-BN administered subcutaneou

236 week, open-label, multisite, within-subject, dose-escalation study of oral leniolisib to assess safet

237 This was a single institution dose-escalation study of pralatrexate plus romidepsin de

238 ralizes IFNalpha, were assessed in a phase I dose-escalation study of single and repeat doses of ront

239 This first-in-man dose-escalation study provides evidence of safety of int

240 The protein dose-escalation study showed that the highest uptake of

241 This phase 1b, open-label, multicentre, dose-escalation study was done at six hospitals (one in

242 A phase 1 dose-escalation study was initiated to examine the safet

243 We conducted a phase I dose-escalation study with (89)Zr-desferrioxamine-IAB2M

244 We tested in a phase 1, open-label, dose-escalation study with 12 months of follow-up in sub

245 stered orally in patients with solid tumors (dose-escalation study).

246 In this phase 1 dose-escalation study, 28 patients with heavily pretreat

247 A total of 41 patients were enrolled in the dose-escalation study, and an additional 23 patients wer

248 In a phase 1 dose-escalation study, combined inhibition of T-cell che

249 open-label, single-arm, first-in-man phase 1 dose-escalation study, eligible patients had advanced AL

250 INTERPRETATION: In this phase 1, dose-escalation study, lorlatinib showed both systemic a

251 Patients and Methods Using a 3 + 3 + 3 dose-escalation study, nine chemotherapy-naive patients

252 double-blind, placebo-controlled, sequential dose-escalation study, patients were randomized 3:1 to r

253 In this prospective dose-escalation study, to optimise disulfiram exposure w

254 In this phase 1 dose-escalation study, we enrolled 4 healthy volunteers

255 In this phase 1 dose-escalation study, we enrolled 81 patients with resi

256 In a phase 1 dose-escalation study, we enrolled patients with advance

257 d solid tumors were treated with AM0010 in a dose-escalation study, which was followed by a renal cel

258 heres has been shown to be safe in a phase 1 dose-escalation study.

259 We did an open-label, single-site, dose-escalation study.

260 fect of disulfiram on HIV transcription in a dose-escalation study.

261 CPD) in an open-label, multicenter, phase 1, dose-escalation study.

262 Dose escalation to 22.5 mg/week was allowed after 8 week

263 oses were 20 mg/m(2), followed thereafter by dose escalation to 36, 45, 56, or 70 mg/m(2).

264 Dose escalation to 480 mg did not identify a maximum-tol

265 ebo or oral cholecalciferol, 2000 IU/d, with dose escalation to elevate serum levels to more than 36

266 ology that used a statistical model to guide dose escalation to identify the maximum-tolerated dose (

267 nation was well tolerated, which allowed for dose escalation to the highest planned dose level (topot

268 -FAZA might be considered a tool for guiding dose escalation to the hypoxic fraction of the tumor.

269 cause toxicity to normal organs, preventing dose escalation to therapeutically active regimens.

270 Lenalidomide dose escalation (to 5 mg or 10 mg per day) was permitted

271 te currently in a phase 1/2a first-in-humans dose escalation trial for patients with relapsed CD37-po

272 samples from a phase I, placebo-controlled, dose escalation trial using recombinant HCV E1E2 with MF

273 Phase 1 dose escalation trial.

274 uble-blinded, randomized, placebo-controlled dose-escalation trial (low and high dose) of a live atte

275 This open-label, single-centre, phase 1a, dose-escalation trial (part of the JAVELIN Solid Tumor t

276 dertook a randomised, double-blind, phase 1, dose-escalation trial between Oct 11, 2011, and Nov 9, 2

277 This phase 1, dose-escalation trial consecutively enrolled children an

278 This open-label, dose-escalation trial in previously treated adult subjec

279 A recent randomized radiation dose-escalation trial in unresectable stage III non-smal

280 We performed an open-label phase 1/2A dose-escalation trial of 3 subcutaneous doses of recombi

281 n the phase 1b, open-label and double-blind, dose-escalation trial of ChAd3-EBO-Z in Mali, we recruit

282 andomised, double-blind, placebo-controlled, dose-escalation trial of intravenous multipotent adult p

283 weeks into a safety and tolerability phase 1 dose-escalation trial of topical sodium nitrite.

284 ouble-blind, randomised, placebo-controlled, dose-escalation trial was done at a single research unit

285 In this open-label, phase 1 dose-escalation trial, patients older than 12 months and

286 who had been enrolled in an initial phase 1 dose-escalation trial, with 2 patients each receiving a

287 e patients received CAR-BCMA T cells in this dose-escalation trial.

288 ic lymphoma were eligible for this phase 1b, dose-escalation trial.

289 o phase 1, placebo-controlled, double-blind, dose-escalation trials of an rVSV-based vaccine candidat

290 ed at our institution on several prospective dose-escalation trials.

291 400 mg/day by mouth for up to 12 months with dose escalation up to 600 mg/day at 3 months if their di

292 Dose escalation used a 3+3 design from a starting dose l

293 Dose escalation was conducted using a 3+3 design with pl

294 A cell dose escalation was conducted, starting at 10(7) total c

295 A standard 3+3 dose escalation was followed by a phase II expansion.

296 Dose escalation was performed using rule-based methods i

297 d in order to increase solubility and enable dose escalation while retaining potency.

298 s; however, the cost-effectiveness ratios of dose escalation with allopurinol-febuxostat sequential t

299 refractory CLL or NHL underwent intrapatient dose escalation with each agent.

300 applications of SIT require a long period of dose escalation with soluble antigen (Ag) and carry a si