ライフサイエンスコーパス: extracranial

1 ation for major hemorrhage (intracranial and extracranial).

2 iple stenotic segments (8 intracranial and 8 extracranial).

3 ere 24 (53.33%) intracranial and 21 (46.67%) extracranial.

4 ies, 71% male) underwent stent placement for extracranial (91%) and intracranial (9%) VAS from 1995 t

5 However, a subgroup of patients with extracranial anatomic triggers appear to benefit from su

6 ediatric cell lines representing 18 distinct extracranial and brain childhood tumor types.

7 etastatic dissemination of cancer cells from extracranial and certain intracranial malignancies into

8 a-arterial treatment (IAT) in the setting of extracranial and intracranial lesions is considered chal

9 the skull) can help differentiate lesions of extracranial and intracranial origins.

10 stenosis at any location and separately for extracranial and intracranial stenoses.

11 anial aneurysms, angioplasty and stenting of extracranial and intracranial stenosis, as well as local

12 tematically investigate, capture, and record extracranial and intracranial venous drainage.

13 ding to previously reported criteria for the extracranial and transcranial US techniques.

14 ts with MS and 42 control subjects underwent extracranial and transcranial venous echo-color Doppler

15 le stenotic segments (16 intracranial and 13 extracranial) and 16 were multiple stenotic segments (8

16 ation in the coronary arteries, aortic arch, extracranial, and intracranial internal carotid arteries

17 b had clinically meaningful intracranial and extracranial antitumor activity in the post-second-gener

18 Overall, intracranial and extracranial antitumor activity were assessed independen

19 Extracranial applications of diffusion-weighted (DW) mag

20 ) atherosclerosis of the aorta and the large extracranial arteries--the internal carotid arteries (IC

21 Extracranial arteriovenous malformation (AVM) is most co

22 Extracranial arteriovenous malformations (AVMs) are char

23 Extracranial arteriovenous malformations (AVMs) are rare

24 east 50% stenosis of a major intracranial or extracranial artery or two or more of the vascular risk

25 Asymptomatic extracranial artery stenosis (ECAS) is a well-known risk

26 atelet Therapy for High-Risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial, a double-

27 ients with stroke compared with an excess of extracranial atherosclerosis and cardioembolic stroke in

28 Therapy for Acute High-Risk Intracranial or Extracranial Atherosclerosis randomized clinical trial w

29 tic stroke was 5.00 (95% CI, 1.69 to 14.76); extracranial atherosclerotic stroke, 1.71 (95% CI, 0.80

30 tic stroke was 5.85 (95% CI, 1.82 to 18.73); extracranial atherosclerotic stroke, 3.18 (95% CI, 1.42

31 We present unique case of a giant extracranial atretic occipital lipoencephalocele in an a

32 ic mutations in MAP2K1 are a common cause of extracranial AVM.

33 tial therapeutic agents for individuals with extracranial AVM.

34 We studied extracranial AVMs in order to identify their biological

35 expression of MMP-9 and MMP-2 in aggressive extracranial AVMs.

36 The main safety outcomes were major extracranial bleeding and ischemic or hemorrhagic stroke

37 Extracranial bleeding occurred in 32 patients (6.3%) in

38 %], respectively; p=0.55); the rate of major extracranial bleeding was higher with enoxaparin than wi

39 Major extracranial bleeding was increased by warfarin therapy

40 Extracranial bleeding was the predominant indication, wh

41 all stroke (ischemic and hemorrhagic), major extracranial bleeding, and death were extracted independ

42 es of ischemic and hemorrhagic stroke, major extracranial bleeding, and death.

43 Ischemic stroke, intracranial hemorrhage, extracranial bleeding, and myocardial infarction identif

44 LAAO use, while history of intracranial and extracranial bleeding, coagulopathy, and falls were asso

45 g rivaroxaban had increased risk of nonfatal extracranial bleeding, fatal ischemic/hemorrhagic events

46 ological intracranial haemorrhage, and major extracranial bleeding.

47 ocation increased major gastrointestinal and extracranial bleeds (0.10%vs 0.07% per year, p<0.0001),

48 Case-fatality from major extracranial bleeds was also lower on aspirin than on co

49 mortality and the decrease in risk of major extracranial bleeds with extended use, and their low cas

50 ent cancer, major vascular events, and major extracranial bleeds, with stratification by age, sex, an

51 Leg, forearm, and extracranial blood flow increased in close association w

52 is a panarteritis that chiefly involves the extracranial branches of the carotid artery.

53 iscussed include hypertension, dyslipidemia, extracranial carotid and intracranial atherosclerotic di

54 n of the supraaortic arteries, including the extracranial carotid and vertebral arteries and intracra

55 Intimal medial thickness of the extracranial carotid arteries (IMT) is related to corona

56 ntified in the renal artery in 294 patients, extracranial carotid arteries in 251 patients, and verte

57 onsecutive patients who underwent CAS of 343 extracranial carotid arteries.

58 thickness and the degree of stenosis in the extracranial carotid arteries.

59 underwent elective (primary) stenting of 271 extracranial carotid arteries.

60 raphic examination of the left ventricle and extracranial carotid arteries.

61 osis is atherosclerotic disease that affects extracranial carotid arteries.

62 or endovascular carotid interventions on the extracranial carotid artery between 2009 and 2014.

63 d to 75% of all strokes; for aortic arch and extracranial carotid artery calcification this incidence

64 Extracranial carotid artery disease accounts for approxi

65 Extracranial carotid artery pseudoaneurysms are rare cas

66 ess invasive method of revascularization for extracranial carotid artery stenosis.

67 hemodynamically significant stenoses of the extracranial carotid artery.

68 contemporary approaches to the management of extracranial carotid atherosclerotic occlusive disease a

69 The presence of extracranial carotid disease (ECD) is associated with le

70 Extracranial carotid disease was defined as cervical int

71 of both endovascular and open techniques for extracranial carotid revascularization.

72 arterectomy remains the standard of care for extracranial carotid stenosis except in specific clinica

73 d symptomatic and asymptomatic patients with extracranial carotid stenosis.

74 for Carotid Endarterectomy With Significant Extracranial Carotid Stenotic Disease).

75 e evaluation of the progression of volume of extracranial carotid vessel walls is feasible with 1.5-T

76 The extracranial carotid, renal, and intracranial arteries w

77 urysm; dissection most often occurred in the extracranial carotid, vertebral, renal, and coronary art

78 0.14 [95% confidence interval, 0.10-0.18] in extracranial carotids, and 0.11 [95% confidence interval

79 No major abnormalities were seen in extracranial cerebral vasculature in 15 patients.

80 It most commonly presents in the renal and extracranial cerebrovascular arteries, either manifestin

81 ion pressure (CPP) can worsen outcome due to extracranial complications of therapy.

82 CPP augmentation protocols that avoid these extracranial complications.

83 ed to the systemic pressure Pa), Ge-relative extracranial conductance.

84 ablish MRI as a gold standard for diagnosing extracranial contributors in headaches.

85 FPs were commonly extracranial (CPM-Net 27.3%; 3D-CNN-TR 42.3%), venous (C

86 om the RVM for the expression of cranial and extracranial cutaneous allodynia, and are consistent wit

87 d hypersensitivity to intracranial-dural and extracranial-cutaneous (noxious and innocuous) somatosen

88 with IMD in the setting of limited or stable extracranial disease (IMD-SE) may represent a unique and

89 ough this shift has translated into improved extracranial disease control and patient outcomes, progr

90 h stratification factors of age, duration of extracranial disease control, number of brain metastases

91 patients had ongoing stable intracranial and extracranial disease for > 2 years.

92 Although extracranial disease is controlled with HER2 inhibitors

93 y, response rate and time to intracranial or extracranial disease progression.

94 ollect granular information on the extent of extracranial disease to identify drivers of mortality an

95 tage IV NSCLC with no more than six sites of extracranial disease who failed early systemic chemother

96 tified by number of metastases and status of extracranial disease.

97 pared with IMD in the setting of progressive extracranial disease.

98 ledge gaps in prevention of stroke caused by extracranial disease.

99 s was CNS only for 3.9% of patients, CNS and extracranial (EC) for 1.8%, and EC only for 31.4%.

100 Exposure to extracranial (EC) surgery early after traumatic brain in

101 ,215 pediatric tumors representing sarcomas, extracranial embryonal tumors, brain tumors, hematologic

102 nal integrity and synapse recovery following extracranial facial nerve transection in mice.

103 odynamic effect of inflow stenosis and intra-extracranial flow diversion, and is a more precise perfu

104 anial aneurysm did not vary with location of extracranial FMD involvement.

105 cy, mutiplicity of intracranial lesions, and extracranial foci or sources of disease.

106 we present an integrated genomic analysis of extracranial GCTs across the age spectrum from 0-24 year

107 Management of paediatric extracranial germ-cell tumours carries a unique set of c

108 4 (11%) versus 78 (9%) patients, significant extracranial haemorrhage occurred in 13 (1%) versus six

109 Yearly risk of extracranial haemorrhage was 1.4% (warfarin) versus 1.6%

110 posite of symptomatic intracranial and major extracranial haemorrhage was small and closely similar b

111 symptomatic intracranial haemorrhage, major extracranial haemorrhage, and all-cause mortality.

112 ratio [HR], 0.92 [95% CI, 0.65 to 1.28]) or extracranial hemorrhage (2.12 vs. 2.63 events per 100 pe

113 c intracerebral hemorrhage (sICH), and major extracranial hemorrhage (ECH) within 90 days.

114 Absolute increases in major extracranial hemorrhage associated with antithrombotic t

115 Compared with warfarin, major extracranial hemorrhage associated with apixaban led to

116 Major extracranial hemorrhage occurred in 1.1% versus 6.1%, re

117 Absolute increases in major extracranial hemorrhage were small (< or =0.3% per year)

118 rrhages, less adverse consequences following extracranial hemorrhage, and a 50% reduction in fatal co

119 omatic intracranial hemorrhage and any major extracranial hemorrhage.

120 -three children (median age, 7.8 years) with extracranial immature teratomas were enrolled on study.

121 nts (symptomatic intracranial or significant extracranial) in the first 14 days after stroke.

122 al principles have recently been extended to extracranial indications such as lung, spine, and liver

123 isk factors for infection were a concomitant extracranial infection (odds ratio, 2.34; 95% CI, 1.01-5

124 Patients with severe extracranial injuries (AIS >/= 3), death within 72 hours

125 e age 10 years without other intracranial or extracranial injuries before or at the time of diagnosis

126 ly after TBI than in controls (patients with extracranial injuries).

127 n 3 years), higher severity intracranial and extracranial injuries, and mechanism of injury related t

128 re TBI (n = 10) with extra-cranial injury or extracranial injury only (EC) (n = 10), 92 inflammation-

129 were psychiatric history, preindex TBI, and extracranial injury severity.

130 thin film of subdural haemorrhage, but lack extracranial injury.

131 sly healthy, and less likely to have a major extracranial injury.

132 syndromes or acute anemic events (AAE), and extracranial internal carotid artery (eICA) stenoses, de

133 d the rate of acute anemic events (AAEs) and extracranial internal carotid artery (ICA) stenosis as r

134 (V(MCA)) to flow velocity in the ipsilateral extracranial internal carotid artery (V(ICA)) was calcul

135 Extracranial internal carotid artery atherosclerotic occ

136 Extracranial internal carotid artery dissections (EICAD)

137 tio of flow in the middle cerebral artery to extracranial internal carotid artery more than or equal

138 for intracranial occlusion, and presence of extracranial internal carotid artery stenosis (>50%) dem

139 sisting of an in situ interposition graft or extracranial-intracranial bypass, is indicated only for

140 Recent studies suggest that extracranial involvement of giant cell arteritis (GCA) m

141 iffers drastically from microenvironments of extracranial lesions, imposing a distinct and profound s

142 of CSF in mice occur along cranial nerves to extracranial lymphatic vessels.

143 t 35 years, survival rates for children with extracranial malignant germ cell tumors (GCTs) have incr

144 ced stages of neuroblastoma, the most common extracranial malignant solid tumor of the central nervou

145 Neuroblastoma (NB) is the most common extracranial malignant solid tumor seen in children and

146 Neuroblastoma is the most common extracranial malignant tumor of childhood, accounting fo

147 ectly, via either cerebrovascular changes or extracranial measurements of electrical/magnetic signals

148 us RNA-seq in 22 treatment-naive MBMs and 10 extracranial melanoma metastases (ECMs) and matched spat

149 tatus, EGFR exon 19 mutation, and absence of extracranial metastases were associated with improved OS

150 arnofsky performance score, age, presence of extracranial metastases, and number of brain metastases,

151 : patient age, Karnofsky Performance Status, extracranial metastases, and number of brain metastases.

152 Absence of extracranial metastases, Karnofsky performance score >/=

153 ms that immunosuppression is also present in extracranial metastases.

154 outcomes in patients with breast cancer and extracranial metastases.

155 ER2-positive or triple-negative subtypes and extracranial metastases.

156 in HER2-positive breast cancer patients with extracranial metastases.

157 CI, 0.89-2.08 years) followed by those with extracranial metastasis (2.16 years; 95% CI, 1.87-2.58 y

158 nvasion, recurrence, and, in rare instances, extracranial metastasis.

159 f death compared with those with concomitant extracranial metastasis.

160 eatment with curative intent, three or fewer extracranial metastatic lesions on choline positron emis

161 g haematological malignancies), one to three extracranial metastatic lesions, a disease-free interval

162 8 (50%) of 76 patients with intracranial and extracranial metastatic melanoma.

163 and heterogeneity between leptomeningeal and extracranial metastatic sites.

164 ancer Study Group centers with biopsy-proven extracranial MT and IT and no prior chemotherapy.

165 Notably, Extracranial near-infrared light irradiation of the moto

166 Neuroblastoma, the most common solid extracranial neoplasm in children, is remarkable for its

167 inal primary afferent neurons than analogous extracranial neurons, making them potentially productive

168 amplifications (1% versus 13%, P = 0.008) in extracranial NGS specimens, with otherwise similar genom

169 in children aged 5 to 18 years with primary extracranial, nonhematopoietic solid malignant tumors th

170 f placebo in pediatric patients with primary extracranial, nonhematopoietic solid malignant tumors th

171 Patients with isolated extracranial occlusions were not included.

172 tion study of patients with solid cancer and extracranial oligometastases treated with SABR.

173 of imaging before treatment in patients with extracranial oligometastases.

174 In patients with extracranial oligometastatic cancer, use of SABR was ass

175 n, intracranial stenosis is more common than extracranial one, anterior circulation stenosis is more

176 ssors, acute neurosurgical intervention, and extracranial operation.

177 ute brain infarction, 23.2% had at least one extracranial or intracranial stenosis of 50% or more, an

178 s emerged between MS and non-MS subjects for extracranial or intracranial venous flow rates.

179 econdary event related to atherosclerosis of extracranial or intracranial vessels.

180 rior cerebral artery involvement) or tandem (extracranial or intracranial) ICA and M1 occlusion subgr

181 Functional and morphologic changes in extracranial organs can occur after acute brain injury.

182 ce similar challenges to brain metastases of extracranial origin, and vice versa.

183 igeminal primary afferent fibers innervating extracranial orofacial structures (such as the cornea, n

184 acranial ORR (IC-ORR) was 56.1% (42.4-69.3), extracranial ORR (EC-ORR) was 36.7% (28.7-45.3), median

185 I setting, with elevated intracranial versus extracranial ORR, particularly in patients with fewer li

186 Patients with TBI, extracranial orthopedic injuries (orthopedic controls),

187 In most cases the extracranial part of the carotid artery is affected; the

188 over 1 year are more likely to suffer severe extracranial, particularly abdominal, injuries.

189 t duplex ultrasonographic examination of the extracranial parts of the carotid arteries.

190 his study was to determine whether there are extracranial pathophysiologies in these headaches.

191 ides the first set of evidence for localized extracranial pathophysiology in CM.

192 erior dura through multiple intracranial and extracranial pathways, and sensitization of central cerv

193 It is the most common extracranial pediatric solid tumor and the most common n

194 Neuroblastoma (NB) is the most common extracranial pediatric solid tumor with an undifferentia

195 Neuroblastoma, the most prevalent extracranial pediatric solid tumor, arises from neural c

196 Neuroblastoma, the most common extracranial pediatric solid tumor, is responsible for 1

197 monstrated in neuroblastoma, the most common extracranial pediatric solid tumor, where MYCN amplifica

198 diameter underpinned the augmented limb and extracranial perfusion.

199 nges at the skull base and continued through extracranial periorbital, olfactory, nasopharyngeal and

200 Secondary outcomes included extracranial PFS (ecPFS) and intracranial PFS (icPFS) as

201 types, correlations of intracranial PFS and extracranial PFS with OS were consistently high despite

202 Non-OS end points included intracranial PFS, extracranial PFS, PFS, time to ICP, time to ECP, and any

203 the right/left internal jugular veins in the extracranial plane and the superior sagittal sinus (SSS)

204 To determine whether binding to an extracranial pool of 5-HT transporters contributes to th

205 Manipulation of intra-extracranial pressure gradient ICP-Pe can augment intrac

206 It also identified 82% of extracranial primary tumor sites, of which 55% were foun

207 lation of intracranial progression (ICP) and extracranial progression (ECP) events with overall survi

208 Extracranial progression was observed in 800 patients (5

209 with placebo, among pediatric patients with extracranial progressive solid malignant tumors .

210 cerebral bv, the external carotid artery, an extracranial proximal SCG target, showed no change in NG

211 therapy compared with those without previous extracranial radiotherapy (0.59 [95% CI 0.36-0.96], p=0.

212 therapy compared with those without previous extracranial radiotherapy (HR 0.50 [0.30-0.84], p=0.0084

213 38 (39%) of 97 patients received extracranial radiotherapy and 24 (25%) of 97 patients re

214 3]) and for patients who previously received extracranial radiotherapy compared with those without pr

215 7]) and for patients who previously received extracranial radiotherapy compared with those without pr

216 der tight experimental control, noninvasive, extracranial recordings can recover mesoscopic traveling

217 exhibit unusual distributions compared with extracranial regions.

218 In cohort B, the extracranial response rate was 38% (95% CI, 25%-52%), ti

219 In cohort A, the extracranial response rate was 48% (95% CI, 31%-66%), me

220 n and isolated anodal vmPFC stimulation with extracranial return electrodes improved time reproductio

221 Extracranial rhabdoid tumours are rare, and often occur

222 ent was ICA, present in 14 (66.6%) out of 21 extracranial segments.

223 n to the human olfactory neuroepithelium, an extracranial site supplying input to the olfactory bulbs

224 sk of all-cause mortality, whereas 3 or more extracranial sites of disease (HR, 1.85; 95% CI, 0.64-5.

225 s delivery of ablative doses of radiation to extracranial sites.

226 scans for identifying NB in soft tissue and extracranial skeletal structures, for revealing small le

227 aging metric with excellent repeatability in extracranial soft tissues across a wide range of tumor s

228 ent diffusion coefficient (ADC) estimates in extracranial soft-tissue diffusion-weighted magnetic res

229 es are a frequent challenge in patients with extracranial solid cancers.

230 NBL, the most common extracranial solid malignant tumor in children, covers a

231 Neuroblastoma is the most common extracranial solid tumor and accounts for ~10% of pediat

232 Neuroblastoma is the most common pediatric extracranial solid tumor and is derived from trunk neura

233 Neuroblastoma, the most frequent extracranial solid tumor in children, harbors the amplif

234 mpathetic nervous system, is the most common extracranial solid tumor in children.

235 Neuroblastoma is the most commonly diagnosed extracranial solid tumor in children.

236 Neuroblastoma is the most common extracranial solid tumor in infants, arising from develo

237 Neuroblastoma is the most common extracranial solid tumor of childhood, and survival rema

238 Neuroblastoma (NB), the most common extracranial solid tumor of childhood, is responsible fo

239 children with neuroblastoma, the most common extracranial solid tumor of childhood.

240 l crest progenitor cells, is the most common extracranial solid tumor of childhood.

241 Neuroblastoma is the most common extracranial solid tumor of childhood.

242 ly expressed in neuroblastoma (NB), a lethal extracranial solid tumor of childhood.

243 Neuroblastoma, the most common extracranial solid tumor that occurs in early childhood,

244 ral crest (NC), is the most common pediatric extracranial solid tumor.

245 Neuroblastoma is the most common childhood extracranial solid tumor.

246 encing data for 1,044 pediatric leukemia and extracranial solid tumors and integrated paired tumor wh

247 otherapy dose of cediranib for children with extracranial solid tumors is 12 mg/m(2)/d administered o

248 ic nervous system tumors are the most common extracranial solid tumors of childhood and include neuro

249 variants (SVs) as risk factors for pediatric extracranial solid tumors using germline genome sequenci

250 ) recommendations in pediatric patients with extracranial solid tumors.

251 ger with high-risk, recurrent, or refractory extracranial solid tumors.

252 ma (HR-NB) is the most frequent, aggressive, extracranial solid tumour in childhood.

253 NB is the most common extracranial solid tumour in children, accounting for ~1

254 population in terms of age and frequency of extracranial sources of cerebrovascular disease.

255 mmunication of the subarachnoid space to the extracranial space, usually a paranasal sinus.

256 anial inflow pressure (Pd) and reverse intra-extracranial steal.

257 as higher for intracranial stenosis than for extracranial stenosis (ten (16%) of 64 patients vs one (

258 For extracranial stenosis alone the HR was 0.63 (95% CI 0.27

259 l stenosis), 115 patients from VAST (96 with extracranial stenosis and 19 with intracranial stenosis)

260 , including 179 patients from VIST (148 with extracranial stenosis and 31 with intracranial stenosis)

261 Stenting for extracranial stenosis might be beneficial, but further l

262 Most commonly involved extracranial stenosis segment was ICA, present in 14 (66

263 (46 with intracranial stenosis and 122 with extracranial stenosis) were randomly assigned to medical

264 nial stenosis from SAMMPRIS (no patients had extracranial stenosis).

265 (64 with intracranial stenosis and 122 with extracranial stenosis).

266 with higher risks for intracranial than for extracranial stenosis.

267 cerebral perfusion pressure (CPP) because of extracranial stenosis.

268 holesterolemia are the major risk factors of extracranial stenosis.

269 higher risk for intracranial, compared with extracranial, stenosis.

270 a greater side effect profile compared with extracranial stimulation, though all forms of stimulatio

271 vents: stroke, transient ischemic attack, or extracranial systemic arterial embolism.

272 son with atrial fibrillation-related stroke, extracranial systemic embolic events (SEEs) remain poorl

273 xy to deliver a high dose of radiation to an extracranial target in the body in a single dose or a fe

274 (two, 2-3; p=0.041) and more frequently had extracranial thrombosis (31 [44%] of 70 patients) compar

275 High doses of AZ10419369 exerted an extracranial tissue vasoconstriction that was comparable

276 ine headache triggered by pathophysiology of extracranial tissues, such as muscle tenderness and mild

277 iated pain but also nociceptive responses in extracranial tissues.

278 Low levels of accumulation were measured in extracranial tissues.

279 Consequently, a trial of extracranial-to-intracranial (EC/IC) arterial bypass for

280 s of < or =15 microg/dL (25th percentile for extracranial trauma patients) or one cortisol of < 5 mic

281 y limit the interpretability of noninvasive, extracranial traveling wave data, sparking debates about

282 Neuroblastoma is a pediatric extracranial tumor and a major cause of death in childre

283 tumor stem cell markers for many intra- and extracranial tumor entities.

284 Neuroblastoma (NB) is the most common extracranial tumor in children.

285 Neuroblastoma is the most commonly diagnosed extracranial tumor in the first year of life.

286 meningioma patients but one with an atypical extracranial tumor showed high uptake of DOTATOC.

287 ession in the neovasculature of the primary, extracranial tumor.

288 f adult cancer, the reported experience with extracranial tumors of childhood is limited.

289 Comparative NGS profiling of intra- and extracranial tumors suggest that CNS dissemination is dr

290 Patients with extracranial tumors, like lung, breast, and skin cancers

291 Notably, unlike most extracranial tumors, STING expression is absent in the m

292 n metastases (BrMs) originating from diverse extracranial tumors.

293 ear whether this is mediated by an excess of extracranial vascular disease (i.e. atherosclerosis) and

294 Patients received either balloon or sham extracranial venoplasty and were followed for 48 weeks.

295 No significant differences in the extracranial venous systems between MS patients and HC s

296 The commonest occlusive sites were: extracranial vertebral artery (52 patients, 15 bilateral

297 d by thromboembolism from an intracranial or extracranial vessel, the heart, or the placenta.

298 ne differences between cerebral arteries and extracranial vessels and partly explain the technical ch

299 seen in larger cerebral vessel walls nor in extracranial vessels.

300 und among patients undergoing imaging of the extracranial vessels; however, there are no large studie