ライフサイエンスコーパス: prolongation

1 electrocardiogram findings (arrhythmia or QT prolongation).

2 tribute equally to action potential duration prolongation.

3 with Ca(2+) overload leading to even greater prolongation.

4 Ca(2)(+)-handling and action potential (AP) prolongation.

5 ese medications due to corrected QT interval prolongation.

6 T score was correlated with drug-induced QTc prolongation.

7 r reverse use dependency of action potential prolongation.

8 ssor responses, tachycardia, and QT interval prolongation.

9 rate pathogenic inhibitory Abs and cause QTc prolongation.

10 A/Ro Ab-positive sera from patients with QTc prolongation.

11 ng QT syndrome (LQTS) is characterized by QT prolongation.

12 ognized risk of dosage-dependent QT interval prolongation.

13 the surface electrocardiogram as QT interval prolongation.

14 and management of autoimmune-associated QTc prolongation.

15 bradycardia and PQ interval and QRS complex prolongation.

16 therapy increased lethality and QTc interval prolongation.

17 ole of anti-Ro Abs in the development of QTc prolongation.

18 a plausible explanation of action potential prolongation.

19 r block-induced ventricular action potential prolongation.

20 seline, 30% (n=1528) of participants had QRS prolongation.

21 ent, sedation, or clinically significant QTc prolongation.

22 were associated with the development of QRS prolongation.

23 rol arm did not have an increased risk of QT prolongation.

24 ssociated with a low incidence of infant QTc prolongation.

25 ecause of a higher propensity to develop QTc prolongation.

26 pressure control on the risk of incident QT prolongation.

27 al medicines are associated with QT interval prolongation.

28 (Na) by Cav3-S141R contribute equally to APD prolongation.

29 hospital length of stay (7 vs 6 d; relative prolongation, 1.10; p = 0.02) compared with the no-delay

30 ere greater with versus without baseline QRS prolongation: 12.6% (95% confidence interval [CI], 11.0-

31 mbocytopenia (13%), and electrocardiogram QT prolongation (13%).

32 hospital discharge in 46 (27%) because of QT prolongation (14%), torsades de pointe or polymorphic ve

33 L (43.52 to 53.51; paliperidone) and for QTc prolongation (15 467 participants) from -2.21 ms (-4.54

34 24%), as well as dose-related, transient QTc prolongation (17%).

35 herapy, MK-8776 was well tolerated, with QTc prolongation (19%), nausea (16%), fatigue (14%), and con

36 ndrome (17%), all-grade electrocardiogram QT prolongation (26%), and grade >= 3 leukocytosis (9%).

37 ily associated with bedaquiline use, and QTc prolongation (43%).

38 more prevalent in people with epilepsy (QTc prolongation: 5% vs 0%; p=0.002; ERP: 34% vs 13%, p<0.00

39 biphasic APD response occurred, with initial prolongation (50.9 +/- 5.1 ms at t = 0 s vs. 60.6 +/- 4.

40 ogical changes such as action potential (AP) prolongation (~50%), reduced L-type calcium channel (LCC

41 ily associated with bedaquiline use, and QTc prolongation 6/14 (43%).

42 ; P=0.007) and activation recovery intervals prolongation (69+/-32 versus 39+/-29 versus 21+/-12 ms;

43 Drug-induced QT interval prolongation, a risk factor for life-threatening ventric

44 Despite the absence of manifest QT prolongation, adolescent anorexic females have impaired

45 es of E-pore peptide Abs and significant QTc prolongation after immunization.

46 redicted to be primarily responsible for APD prolongation, although increased I(Ca,L) and late I(Na)

47 with baseline QT interval to drug-induced QT prolongation and arrhythmias is not known.

48 t (IKr) blockade to predict long QT syndrome prolongation and arrhythmogenesis.

49 A simplified approach to monitoring for QT prolongation and arrythmia was implemented on April 5.

50 dium channel, is associated with PR-interval prolongation and atrial fibrillation (AF).

51 l and are associated with corrected QT (QTc) prolongation and complex ventricular arrhythmias.

52 l role for the rosette structure in activity-prolongation and coordination.

53 of the intercellular cleft can suppress APD prolongation and EADs in the presence of Na(+) channel m

54 Severe QTc prolongation and ERP were more prevalent in people with

55 show similar problems including QTc interval prolongation and hypothermia.

56 I(NaL) in HF significantly contributes to AP prolongation and increased short-term variability of AP

57 ortion of the variability in drug-induced QT prolongation and is a significant predictor of drug-indu

58 We evaluated (1) the frequency of QTc prolongation and its association with inflammatory marke

59 mal resting QTc values and only developed QT prolongation and malignant arrhythmias after exposure to

60 edema exacerbated action potential duration prolongation and produced EADs, in particular, at slow p

61 h V4, with either persistent or transient QT prolongation and severe disease expression of exercise-i

62 ain may contribute to ischemia-associated QT prolongation and sudden cardiac death.

63 QT prolongation and TdP are a risk in men receiving enzalut

64 Although prolongation and then shortening of visual evoked potent

65 the remaining 199, all with either clear QTc prolongation and/or typical repolarization abnormalities

66 h early childhood cardiac arrest, extreme QT prolongation, and a negative family history.

67 were potential liver toxicity, corrected QT prolongation, and adrenal insufficiency.

68 discontinue any of the medications due to QT prolongation, and arrhythmogenic death.

69 ts causing hypertension, thromboembolism, QT prolongation, and atrial fibrillation.

70 by extensive T-wave inversions, transient QT prolongation, and severe disease expression of exercise-

71 ERP and severe QTc prolongation appear to be more prevalent in people with

72 Indeed, progressive corrected QT prolongation, arrhythmias, and ischemic changes were not

73 ated systemic and pulmonary hypertension, QT prolongation, arrhythmias, pericardial disease, and radi

74 The RIT prolongation as a measure of changing DA function may be

75 We defined QRS prolongation as QRS>/=100 ms.

76 in HRV over 24h at 10 dpa, accompanied by QT prolongation as well as diurnal variations, followed by

77 %) patients, including five instances of QTc prolongation-assessed as possibly related to BDQ and/or

78 The prominent AP prolongation at action potential duration at 30% repolar

79 icity CMR parameter was T(2) relaxation-time prolongation at week 6 (2 weeks after the third dose).

80 erolemia is associated with action potential prolongation because of increased I(Ca) and reduces occu

81 thal cardiac consequences of drug-induced QT prolongation because they have a substantial cardiovascu

82 yte migration and the retraction of neuronal prolongations, both processes in which internal forces a

83 of age, corresponding to the presence of PR prolongation, but not P1, suggesting, at least in part,

84 on occurs in the heart and contributes to QT prolongation by altering cardiac sodium current properti

85 resynaptic spikes without preventing further prolongation by brief depolarizing somatic prepulses.

86 Additionally, chronotropic as well as QT-prolongation causing reference compounds were used for v

87 ough use of these medications resulted in QT prolongation, clinicians seldomly needed to discontinue

88 At this early time point, isolated T(2) prolongation correlated with intracardiomyocyte edema se

89 Underlying abnormalities include QT prolongation, delayed repolarization from downregulation

90 h autoimmune diseases and corrected QT (QTc) prolongation directly target and inhibit the human ether

91 f the control VEP demonstrated around 2-fold prolongation during active disease.

92 Consistent with QT prolongation, epileptic rats had longer ventricular acti

93 PR prolongation (first degree AV block) was present at 4 we

94 [7%]), sepsis or septic shock (11 [5%]), QT prolongation (five [2%]), and nausea (five [2%]) in the

95 models and led to reduced relative survival prolongation following temozolomide treatment of orthoto

96 ociated with slow conduction rather than APD prolongation form a potent substrate for arrhythmogenesi

97 e inversions, and 10 (53%) have transient QT prolongation > 480 ms.

98 was 403 (standard deviation, 30) ms, and no prolongation >450 ms occurred.

99 One patient (7%) had QTc prolongation >500 milliseconds and died 20 months after

100 were used to compare the risk of incident QT prolongation (>460 ms in women or >450 ms in men) in the

101 g doxorubicin therapy upon detection of T(2) prolongation halted progression to LV motion deteriorati

102 r, innate susceptibility to PM-associated QT prolongation has not been characterized.

103 We revealed Amiodarone-mediated QTc prolongation, HR reduction and HRV increase otherwise ma

104 e genetic susceptibility to PM-associated QT prolongation in a multi-racial/ethnic, genome-wide assoc

105 QRS prolongation in African Americans was associated with in

106 is underscored by evidence that QT interval prolongation in diabetes mellitus also may result from c

107 Exercise testing is useful in unmasking QT prolongation in disorders associated with abnormal repol

108 Prolongation in fibrinolysis was consistent across plasm

109 ory Abs to the HERG E-pore region induce QTc prolongation in immunized guinea-pigs by targeting the H

110 Such marked action potential prolongation in individual cardiac cells, in turn, is ac

111 0.75; 95% CI, 0.59 to 0.96; P = .016) and a prolongation in median PFS from 15.6 months with letrozo

112 c cardiac models revealed that transient APD prolongation in mouse allowed for greater and more rapid

113 ipoprotein (LDL), L5, is correlated with QTc prolongation in patients with coronary artery disease (C

114 w that L5 was positively correlated with QTc prolongation in patients with ischemic heart disease.

115 ctors associated with the development of QRS prolongation in patients with normal baseline QRS.

116 y alter susceptibility to PM10-associated QT prolongation in populations protected by the U.S. Enviro

117 gree of conduction delay in the RVOT and not prolongation in repolarization time.

118 rsions in the precordial leads, transient QT prolongation in some, and recurrent ventricular arrhythm

119 Additionally, SNS produced APD(80) prolongation in the apex of control but not DBH-Sap hear

120 The percentages of APD prolongation in the last 4 hearts at 2000 ms PCL after a

121 ent change causing action potential duration prolongation in the presence of Cav3-F97C is the slowly

122 Grade 3 QT prolongation in the quizartinib group was uncommon (eigh

123 elevation and activation recovery intervals prolongation in the RVOT, RV, or left ventricle.

124 Prolongation in transisthmus conduction time and differe

125 r cleft narrowing or expansion regulates APD prolongation; in contrast, modulating the bulk interstit

126 20, p<0.1) were independent predictors of QT-prolongation.Incidence of LTA during hospitalization was

127 Factors associated with developing QRS prolongation included age, male sex, prior myocardial in

128 currents in HF promote action potential (AP) prolongation, increased short-term variability of AP rep

129 ventricular tachycardia in the absence of QT prolongation, indicating a novel proarrhythmic syndrome.

130 omputational model to test the degree of APD prolongation induced by small electrical perturbations i

131 QT interval prolongation is a heritable risk factor for ventricular

132 with prolongation of the QT interval that QT prolongation is an accepted surrogate marker for arrhyth

133 ause of underlying action potential duration prolongation is incompletely understood.

134 he animal model of autoimmune-associated QTc prolongation is the first to provide strong evidence for

135 Electrocardiographic QT interval prolongation is the most widely used risk marker for ven

136 phic ventricular tachycardia (VT) without QT prolongation is well described in patients without struc

137 RD trial is not likely to be explained by QT prolongation leading to lethal ventricular arrhythmias.

138 Gs for three markers of SCA risk: severe QTc prolongation (male >450 ms, female >470 ms), Brugada ECG

139 omoting conduction slowing as opposed to APD prolongation mark the chronic phase.

140 Severe activated partial thromboplastin time prolongation may be a marker of combined hyperfibrinolyt

141 This prolongation may result from periodic drug-binding to a

142 n=1 [1%]; imatinib group, n=1 [1%]), and QT prolongation (nilotinib group, n=1 [1%]; imatinib group,

143 QT prolongation occurred in 49 (3%) patients given neratini

144 Na-L prolonged APD acutely but no additional prolongation occurred on chronic superfusion.

145 vacuolization, demonstrating that early T(2) prolongation occurs at a reversible disease stage.

146 in held or discontinued due to an average QT prolongation of 60.5+/-40.5 ms from a baseline QTc of 47

147 nism may be important for the maintenance or prolongation of a healthy CNS.

148 Prolongation of AA catabolism in P. falciparum-infected

149 transport of Abeta, resulted in significant prolongation of Abeta40 half-life, but only in the latte

150 Patch clamp experiments showed prolongation of action potential duration (APD) in TAC a

151 stemizole or sertindole caused heterogeneous prolongation of action potential duration and a high inc

152 hat Kir2.1-52V is associated with a dramatic prolongation of action potential duration with evidence

153 fterdepolarizations and leads to substantial prolongation of action potential duration.

154 reased variation in and a nonsignificant 15% prolongation of action potential duration.

155 ciated with reduction of TASK-1 currents and prolongation of action potential durations in atrial car

156 ose- and time-dependent robust and sustained prolongation of activated partial thromboplastin time an

157 frequency and singularity point density, and prolongation of AFCL.

158 diators contributes to the amplification and prolongation of anaphylaxis.

159 ithout EADs (no-EAD response) showed gradual prolongation of AP duration (APD), and were annihilated

160 ny of the modified residues into RE31 causes prolongation of aptamer stability in human serum.

161 gical mechanism underlying AF prevention was prolongation of atrial effective refractory periods, at

162 The prolongation of auditory obligatory and novelty ERPs in

163 n ck2beta(-/-) mice, accompanied by a slight prolongation of bleeding time.

164 Prolongation of bronchopulmonary C-fiber-mediated apnea

165 A large number of drugs can induce prolongation of cardiac repolarization and life-threaten

166 he TNF-alpha-inflamed cremaster muscle and a prolongation of chemokine-dependent leukocyte adhesion c

167 The prolongation of CIT is associated with an increase in DG

168 However, adhiron A6 abolished C3-induced prolongation of clot lysis, reducing mean lysis time fro

169 rior analyses of human fIIa(MZ), significant prolongation of clotting times was observed for fII(MZ)

170 Prolongation of either the QT interval or the corrected

171 ly enhanced with an increase of pressure and prolongation of encapsulation time.

172 iii) enhanced F-actin formation; (iv) marked prolongation of eosinophil lifespan (via a NF-kappaB and

173 ce homology with C3 and abolished C3-induced prolongation of fibrin clot lysis by interfering with C3

174 Cell-cycle analysis shows prolongation of G0/G1 with LRH-1 silencing, consistent w

175 rnal age in C57BL/6J mice is associated with prolongation of gestation and length of labour.

176 was no association between unit policies and prolongation of gestation in a multilevel survival analy

177 r CTLA4Ig induced significant and equivalent prolongation of graft survival in both groups of chimeri

178 particular transitional B cells, can promote prolongation of graft survival, a function dependent on

179 but failed to induce Treg, resulting in mild prolongation of graft survival.

180 py for prevention of allograft rejection and prolongation of graft survival.

181 D910A/D910A) , recipients exhibit indefinite prolongation of heart allograft survival.

182 In vivo, the atropine-dependent prolongation of heart rate increase was blunted in PDE4D

183 t accumulation of myeloid cells required for prolongation of heart transplant survival induced by cos

184 When subjected to PH, Wls-LKO showed prolongation of hepatocyte proliferation for up to 4 day

185 equiring further surgery and/or resulting in prolongation of hospitalization of at least 24 h, and/or

186 KA), rather than PKCepsilon, dependence; (3) prolongation of hyperalgesia induced by an activator of

187 Loss of Arrb2 also results in prolongation of inflammatory pain and neuropathic pain a

188 a (OIH) and neuroplasticity characterized by prolongation of inflammatory-mediator-induced hyperalges

189 decay, decreased ANAPC1 protein levels, and prolongation of interphase.

190 significant increase in RD progression after prolongation of interruptions by sitting upright.

191 cin, and this treatment leads to significant prolongation of islet allograft survival in allosensitiz

192 protection of the cytokine's active site and prolongation of its half-life.

193 o have robust antithrombotic efficacy and no prolongation of kidney bleeding time.

194 de a key, cost-effective contribution to the prolongation of life expectancy and quality.

195 a multidisciplinary approach enables a safe prolongation of liver preservation and overnight organ c

196 on (NMP) bears the potential for significant prolongation of liver preservation before transplantatio

197 Intriguingly, Wnt5a-LKO did not display any prolongation of LR because of compensation by other cell

198 Since prolongation of mitosis was shown to affect cell viabili

199 sgenic C. elegans models correlated with the prolongation of MT induction time and that knockdown of

200 racking with light loggers suggested diurnal prolongation of nocturnal flights and common non-stop fl

201 The clinically meaningful prolongation of overall survival and favourable safety p

202 diograms demonstrated that MetS-VLDL induced prolongation of P wave (P = 0.041), PR intervals (P = 0.

203 d susceptibility to AF in association with a prolongation of P-wave duration, increased atrial refrac

204 of host and parasite genotypes as risks for prolongation of parasite clearance kinetics, measured ev

205 symptoms of myelofibrosis (MF), and possible prolongation of patients' survival, some have disease th

206 Though the exact reason for the prolongation of post treatment symptoms are not known, t

207 rs = 0.364-0.802 vs 0.364-0.813; P < 0.001), prolongation of postoperative stay (rs = 0.802 vs 0.830;

208 tory chronic lymphocytic leukemia (CLL) with prolongation of progression-free and overall survival.

209 k hyperdiploid MM and identify patients with prolongation of progression-free survival.

210 ing nociceptor neuroplasticity manifested as prolongation of prostaglandin E(2) (PGE(2)) hyperalgesia

211 administration of fentanyl and confirmed by prolongation of prostaglandin E(2) (PGE(2)) hyperalgesia

212 to TLR4 mRNA (TLR4 AS-ODN) prevented OIH and prolongation of prostaglandin E(2) hyperalgesia (priming

213 O induced mechanical hyperalgesia and marked prolongation of prostaglandin E2 (PGE2) hyperalgesia, a

214 els back to the terminal to mediate a marked prolongation of prostaglandin E2-induced hyperalgesia.

215 responses, or tachycardia but abolished the prolongation of QT interval.

216 formation, and affects the initiation and/or prolongation of remission stages of UC.

217 ay, E. coli may affect the initiation and/or prolongation of remission stages of UC.

218 a series of repeated ketamine infusions, and prolongation of response with maintenance infusions.

219 Prolongation of rituximab maintenance beyond 2 years is

220 food coating proved to be efficient for the prolongation of shelf life of Ricotta cheese.

221 tributions were the single best predictor of prolongation of sIPSCs.

222 However, prolongation of skin graft survival was lost when B cell

223 Prolongation of spontaneously occurring ripples by optog

224 st responses (0% cures but two- to threefold prolongation of survival compared with negative controls

225 tumors showed no reduction in tumor size or prolongation of survival following immunotoxin treatment

226 renal function and further contribute to the prolongation of survival.

227 improved management of systemic disease and prolongation of survival.

228 enhanced systolic function without excessive prolongation of systolic ejection time, which may compro

229 p < 0.005) and was negatively related to the prolongation of tactile latencies (p < 0.01); tactile gn

230 associated mutation G1349D all abolished the prolongation of taucf at pHi 6.3.

231 tudies revealed epicardial (EPI)-predominant prolongation of the action potential duration (APD) at 5

232 the peak and late sodium currents leading to prolongation of the action potential duration and an inc

233 ltered intracellular Ca(2+) cycling causes a prolongation of the action potential, as determined by w

234 (F((8,245)) = 2.02, p = 0.04), suggesting a prolongation of the antidepressant effects of ketamine b

235 sponses such as immune system activation and prolongation of the blood coagulation pathway.

236 diovascular drugs frequently cause excessive prolongation of the cardiac action potential (AP) and le

237 Prolongation of the corrected QT interval and elevation

238 g set of cancer therapeutics that can induce prolongation of the corrected QT interval.

239 e data indicate a strong correlation between prolongation of the decay time course of sIPSCs and pote

240 We observed prolongation of the early stages of action potential (AP

241 ween Galphaq and GRK2 were associated with a prolongation of the interaction between GRK2 and the M3-

242 Decrement was defined as rate-dependent prolongation of the local ventriculo-atrial time by >30

243 one administration resulted in a significant prolongation of the oestrous cycle and blockade of LH su

244 ng group can easily be removed, allowing the prolongation of the peptide chain at the C-terminus.

245 T2* measured in the soleus muscle, and (3) a prolongation of the posterior tibial vein SvO2 washout t

246 del of temporal lobe epilepsy, and it led to prolongation of the PR interval in ECG recordings in rod

247 The mechanism causing a prolongation of the QT interval during epilepsy remains

248 Several reports have demonstrated that prolongation of the QT interval is associated with sudde

249 ditions can occasionally produce exaggerated prolongation of the QT interval on the electrocardiogram

250 proarrhythmia is so tightly associated with prolongation of the QT interval that QT prolongation is

251 Although prolongation of the QT interval was associated with a 49

252 hERG1 block leads to a prolongation of the QT interval, a phase of the cardiac

253 ension, syncope, dyskinesia, hallucinations, prolongation of the QT interval, and impulse control dis

254 ions alone, or in combination, can lead to a prolongation of the QT interval, possibly increasing the

255 y responsible for delayed repolarization and prolongation of the QT interval.

256 total 5 (11% [95% CI, 4%-24%]) neonates had prolongation of the QTc >2 SD above historical healthy c

257 e leads to HuR detachment and the subsequent prolongation of the SOX2 mRNA half-life.

258 isk of SCD with the QT interval is driven by prolongation of the T-wave onset to T-peak component.

259 transplants showed a significant (p = 0.004) prolongation of their euglycemic period (by 6 weeks; up

260 unctions of most beta-band activity, so that prolongation of these beta episodes, as observed in Park

261 Prolongation of transient porcine chimerism via transgen

262 r mode called open-end growth mode means the prolongation of tube growth from the exposed BN edge sur

263 Prolongation of ventricular depolarization is concentrat

264 F group at 28 days postinjection, there were prolongations of PR interval (after versus before: 130 +

265 Ro antigen-immunized guinea pigs showed QTc prolongation on ECG after developing high titers of anti

266 thrombocytopenia [cohort 2], one grade 3 QT prolongation on electrocardiogram [cohort 3], and one gr

267 Arrhythmias associated with QT prolongation on the ECG often lead to sudden unexpected

268 tients with autoimmune diseases and with QTc prolongation on the ECG target the human ether-a-go-go-r

269 g delayed repolarization seen as QT interval prolongation on the ECG.

270 lengthen the action potential and cause QTc prolongation on the surface ECG.

271 n clears dead cells and matrix debris, while prolongation or expansion of the inflammatory response r

272 ORadj 2.4, 95% CI 1.1 to 5.5) and severe QTc prolongation (ORadj 9.9, 95% CI 1.1 to 1317.7).

273 as associated with more episodes (p = 0.02), prolongation (p = 0.01), and greater cumulative duration

274 patients who developed corrected QT-interval prolongation (p = 0.16), extrapyramidal symptoms (p = 0.

275 ar electrical remodeling and significant QTc prolongation, regardless concomitant antimicrobial thera

276 g follow-up demonstrated higher rates of RIT prolongation relative to those that did not (P < 0.0001)

277 The primary outcome was QT prolongation resulting in Torsade de pointes.

278 outine ECG screening and that those with QTc prolongation should receive counseling about drugs that

279 Hence, they are prone to participate in the prolongation step of the radical chain reactions occurri

280 Such prolongation tends to be seen among patients who require

281 Secondary outcomes included QT prolongation, the need to prematurely discontinue any of

282 pH-dependent, which results in a significant prolongation their half-life.

283 he association of citalopram with cardiac QT prolongation, use of this agent to treat agitation may b

284 python script to identify any mention of QT prolongation, ventricular tachy-arrhythmias and cardiac

285 The arrhythmogenic potential of APD prolongation was also tested as a basis for comparison.

286 After risk adjustment, QRS prolongation was associated with increased mortality (ha

287 The APD prolongation was mediated by an increase of L-type calci

288 QTc prolongation was observed in all patients (by 60 +/- 6 m

289 the full analysis population, the 7.2 months prolongation we noted with the addition of everolimus in

290 re female) revealed that higher rates of RIT prolongation were correlated with AMD severity group ass

291 Overall, higher rates of RIT prolongation were significantly correlated with greater

292 om patients with autoimmune diseases and QTc prolongation were tested on IKr using HEK293 cells expre

293 te kidney failure, and corrected QT interval prolongation, were not significantly different between g

294 nsive glycemic control is associated with QT prolongation, which may lead to ventricular arrhythmias

295 rug-mediated K(v)11.1 blockade results in AP prolongation, which poses an increased risk of sudden ca

296 s leading to different primary causes of APD prolongation, which suggests the use of mutation-specifi

297 eption of asymptomatic corrected QT interval prolongation, which was significantly higher in the dihy

298 limits, with no significant increase in QTc prolongation with increasing courses of DP.

299 ominently featuring cardiac action potential prolongation with paroxysms of life-threatening arrhythm

300 sion to normal rhythm was associated with QT prolongation yet absent proarrhythmia markers for Torsad