ライフサイエンスコーパス: paediatric

1 elopment of safe and effective therapies for paediatric abdominal pain-related functional gastrointes

2 ic bypass for clinically severe obesity at a paediatric academic medical centre in the USA.

3 c significance of key genetic alterations in paediatric ACT and outline a hypothetical model of paedi

4 llance data from 2 studies nested within the Paediatric Active Enhanced Disease Surveillance (PAEDS)

5 ance data from two studies nested within the Paediatric Active Enhanced Disease Surveillance (PAEDS)

6 Relapsed paediatric acute lymphoblastic leukaemia (ALL) has high

7 ases) have been used as first line drugs for paediatric Acute Lymphoblastic Leukaemia (ALL) treatment

8 -, MRI studies, outcome and MOG status of 33 paediatric ADEM prospectively studied were reviewed.

9 potential from umbilical cord (UC-MSCs) and paediatric adipose tissue (ADSCs), while highlighting di

10 The magnitude of cardiovascular morbidity in paediatric, adolescent, and young adult survivors of Hod

11 e true effect of cardiovascular morbidity in paediatric, adolescent, and young adult survivors of Hod

12 Paediatric adrenocortical carcinoma is a rare malignancy

13 tric ACT and outline a hypothetical model of paediatric adrenocortical tumorigenesis.

14 l diseases (AP-FGD) are commonly seen in the paediatric age group.

15 Here, we quantify the heritability of paediatric AIDs (pAIDs), including JIA, SLE, CEL, T1D, U

16 a (HD-ALL) being the most common subgroup of paediatric ALL, its aetiology remains unknown.

17 modifiable clinical practice associated with paediatric allergic disease.

18 of the secular trend of hospitalizations for paediatric allergic reactions, including anaphylaxis, ar

19 ntended for UK specialists in both adult and paediatric allergy and for other clinicians practising a

20 In this pre-clinical study, paediatric AML cells expanded in culture and primary AML

21 lement strategies for quality improvement in paediatric anaesthesia.

22 , and a large variability in the practice of paediatric anaesthesia.

23 improved international collaboration across paediatric and adult cooperative research groups.

24 ype 2 diabetes now poses major challenges to paediatric and adult diabetes services in many countries

25 bstantial morbidity and health-care costs in paediatric and adult onset Crohn's disease.

26 72 countries collected prospective data for paediatric and adult patients with confirmed acute kidne

27 te on the optimal transition of care between paediatric and adult specialists.

28 d understanding of the heterogeneity of both paediatric and adult wheezing.

29 acceptable alternative stem cell source for paediatric and adults requiring a haematopoietic transpl

30 s has been made in the care of patients with paediatric and congenital cardiac disease, optimization

31 e expert members of the European Society for Paediatric and Neonatal Intensive Care; four experts of

32 ration (FDA) guidance for adults was used in paediatrics, and whether paediatric clinical trials appl

33 Absence of consensus for paediatric antibiotic clinical trials is a major barrier

34 Here we use a mouse model mimicking paediatric antibiotic use and find that therapeutic-dose

35 , BREATHE (n = 820, age: 3-22 years, UK) and Paediatric Asthma Gene Environment Study (n = 391, age:

36 dmixture in Latino Americans II, PACMAN, the Paediatric Asthma Gene Environment Study, and the Pharma

37 ubset distribution and activation profile in paediatric asthma using flow cytometry to analyse induce

38 Paediatric B-cell precursor acute lymphoblastic leukaemi

39 five initiatives: an aggregated database of paediatric biological tumour drug targets; molecular pro

40 This child has one of the largest documented paediatric brain sizes, to our knowledge.

41 Medulloblastoma is a highly malignant paediatric brain tumour currently treated with a combina

42 Medulloblastoma (MB) is the most common paediatric brain tumour that arises from cerebellar prec

43 Medulloblastoma is a highly malignant paediatric brain tumour, often inflicting devastating co

44 Intrinsic Pontine Gliomas (DIPGs) are deadly paediatric brain tumours where needle biopsies help guid

45 ed quality of life in long-term survivors of paediatric brain tumours.

46 e urogenital tract represents a considerable paediatric burden, with many defects affecting the lower

47 related mortality is an important outcome in paediatric cancer clinical trials.

48 ional group of experts in supportive care in paediatric cancer developed a consensus-based definition

49 Delphi approach to establish principles for paediatric cancer stage collection.

50 t of total cumulative burden in survivors of paediatric cancer, with detailed characterisation of lon

51 omatic mutations in epigenetic regulators in paediatric cancer.

52 out how to continue to reduce the burdens of paediatric cancer.

53 The criteria for staging paediatric cancers, however, vary by diagnosis, have evo

54 without the typical bone marrow failure and paediatric cancers.

55 improving the quality of the congenital and paediatric cardiac care, and will also review some of th

56 utional outcomes analysis for congenital and paediatric cardiac surgery.

57 g adequate funding for dedicated, preventive paediatric care and taking action on a nationwide scale

58 services (such as general medicine, HIV, or paediatric care), play an important part for a smaller p

59 We present a paediatric case of infectious mononucleosis in a 13-year

60 Paediatric cataracts have a different pathogenesis, surg

61 ed to have highly credible associations with paediatric CD, of which four variants (rs2066847, rs1252

62 (EEN) is the primary induction treatment in paediatric CD.

63 Paediatric centres had the longest routine waiting times

64 In paediatric cerebral malaria a combination of retinal sig

65 liary atresia, which remains the most common paediatric chronic liver disease and indication for live

66 e European Paediatric Regulation facilitates paediatric class waivers for drugs developed for disease

67 ld be aware of these novel manifestations of paediatric clear cell RCC.

68 nt improvements in our research practices in paediatric clinical oncology research.

69 The comparison between paediatric clinical trials and adult EMA and FDA guidanc

70 adults was used in paediatrics, and whether paediatric clinical trials applied consistent definition

71 had never been placed in an institution from paediatric clinics and schools in Bucharest as a compara

72 lism and tested its diagnostic efficacy in a paediatric cohort of 30 undiagnosed patients presenting

73 in an independent, co-located sample of four paediatric cohorts consisting of 203 food allergic cases

74 n independent sample group derived from four paediatric cohorts, total n=533 (n=203 food-allergic, n=

75 es were conducted for 20 SNPs in 10 genes of paediatric Crohn's disease (CD) and for 8 SNPs in 5 gene

76 the movement of patients attending adult and paediatric cystic fibrosis centres, and compared these w

77 We analysed paediatric data from this survey, aiming to calculate th

78 drugs had a mechanisms of action warranting paediatric development.

79 ite Cryptosporidium to be a leading cause of paediatric diarrhoea, with particularly grave impact on

80 Severe progressive neurological paediatric disease mucopolysaccharidosis III type C is c

81 We retrospectively studied 1199 paediatric donor-recipient pairs with allele-level HLA m

82 Available treatments for paediatric drug-susceptible and drug-resistant tuberculo

83 ajor cause of morbidity and mortality in the paediatric, elderly and immune-compromised populations(1

84 food allergy may impact the presentation of paediatric EoE.

85 od absence epilepsy (CAE) is the most common paediatric epilepsy syndrome and is characterized by fre

86 dysplasia, are common causes of intractable paediatric epilepsy.

87 mly assigned to receive either two units (or paediatric equivalent) of anti-influenza plasma plus sta

88 Management of paediatric extracranial germ-cell tumours carries a uniq

89 medicines are poorly available; one current paediatric formulation utilizes high ethanol concentrati

90 ctive cohort study conducted at two European Paediatric Gastroenterology Units.

91 Recent developments in paediatric gastrointestinal surgery have focused on mini

92 Patient-derived orthotopic xenografts of paediatric GBM, DIPG and adult GBM fail to grow in Nlgn3

93 Paediatric germ-cell tumours differ from the adolescent

94 ally distinct HGG types, including adult and paediatric glioblastoma (GBM), anaplastic oligodendrogli

95 t grows sixfold postnatally and is a site of paediatric gliomas; however, the mechanisms of pontine g

96 rs1800629) were not previously identified in paediatric GWAS.

97 international cooperative study, such as the Paediatric Hepatic International Tumour Trial (PHITT).

98 mparative assessment of treatment results in paediatric hepatoblastoma trials has been hampered by sm

99 In the past 10 or so years, paediatric hepatology has expanded into neighbouring cli

100 inted at by the Mississippi baby experience, paediatric HIV infection has been pivotal to our underst

101 rise in interventions for the elimination of paediatric HIV infection, but the number of uninfected i

102 s exist for HIV populations and conventional paediatric HIV medicines are poorly available; one curre

103 ne discovery to generate a potential aqueous paediatric HIV nanotherapy, with clinical translation an

104 Paediatric HIV prevalence across all settings was 15.6%

105 lts have implications for the development of paediatric HIV-1 vaccines.

106 osed bronchiolitis newly admitted into eight paediatric hospital units in the UK (the Bronchiolitis o

107 open-label, non-inferiority trial done at 26 paediatric hospitals and health centres in the USA and C

108 e, club foot, hernia or hydrocele [adult and paediatric]), hydrocephalus, hypospadias, injuries or wo

109 Highly credible SNPs associated with paediatric IBD have also been implicated in adult IBD, w

110 The overall prevalence of paediatric IBD in Sweden was similar to that in earlier

111 ly onset and distinct phenotypic features of paediatric IBD might be due to distinct epigenetic chang

112 ing genetic and epigenetic susceptibility of paediatric IBD will require international collaboration,

113 on in let-7 and miR-124 were associated with paediatric IBD, but not as yet replicated.

114 dies of population-representative samples of paediatric (ie, <15 years) tuberculosis cases.

115 for admission severity of illness using the Paediatric Index of Mortality 2 score, predictors for 5-

116 ctions in adults despite large reductions in paediatric infections.

117 of such cognitive effects in the context of paediatric infectious disease vaccines has received rela

118 the model and makes it harder to eliminate a paediatric infectious disease.

119 liance, Wellcome Trust, European Society for Paediatric Infectious Diseases, and National Institute f

120 e definition algorithms on the prevalence of paediatric inflammatory bowel disease (IBD), Crohn's dis

121 s of genetic and epigenetic associations for paediatric Inflammatory Bowel Disease (IBD).

122 Paediatric inflammatory bowel disease (PIBD), comprising

123 The incidence of early-onset paediatric inflammatory bowel disease is increasing worl

124 HIV prevalence by setting was highest in paediatric inpatient settings (21.1%, 95% CI 14.9-27.3),

125 cted through screening in four key contexts (paediatric inpatient settings, paediatric outpatient set

126 otherapists, neurosurgeons, parents, and the Paediatric Intensive Care Audit Network).

127 ng prepared for admission to a participating paediatric intensive care unit and were expected to need

128 cealed from patients, their parents, and the paediatric intensive care unit personnel responsible for

129 The prevalence of infections was highest in paediatric intensive care units (15.5%, 95% CI 11.6-20.3

130 sis of most genetic diseases in neonatal and paediatric intensive care units (NICU and PICU) is not s

131 pain management practices in the neonatal or paediatric intensive care units, recovery room, and/or f

132 could help prevent bloodstream infections in paediatric intensive care units.

133 led trial of children admitted to 14 English paediatric intensive care units.

134 formation of Wilms' tumour, the most common paediatric kidney cancer.

135 Many paediatric liver conditions are precursors of adult chro

136 Clinical research suggests that paediatric liver disease differs in both severity and ra

137 aematology, and the Japanese Study Group for Paediatric Liver Tumours)-created a shared international

138 Neuroblastoma is a paediatric malignancy that typically arises in early chi

139 prevalent defect in the respiratory chain in paediatric mitochondrial disease.

140 nfections rank second as causes of adult and paediatric morbidity and mortality worldwide.

141 encouraged to decrease tuberculosis-related paediatric mortality in high-burden settings, but this s

142 Material/We retrospectively reviewed 69 paediatric MRI sedations performed over a 5-year period

143 We evaluated all paediatric MRI sedations since installation of an MRI de

144 ears of disease onset were recruited from 15 paediatric MS centres in the USA as part of a case-contr

145 This is a multicentre study done at 11 paediatric MS centres in the USA.

146 stages were combined with a longitudinal US paediatric MS cohort with 181 cases followed for 5 years

147 Idiopathic scoliosis (IS) is a common paediatric musculoskeletal disease that displays a stron

148 astang Foundation, Bath Unit for Research in Paediatrics, National Institute of Health Research, the

149 ement of the central nervous system puts the paediatric neurologist, neurogeneticist, and neurometabo

150 Cases were identified using several sources (paediatric neurologists and trainees, the British Paedia

151 epilepsy), posing diagnostic challenges for paediatric neurologists.

152 cine, CT, USA, we recruited patients from 59 paediatric neurology practices in the USA.

153 atric neurologists and trainees, the British Paediatric Neurology Surveillance Unit, paediatricians,

154 We describe a national paediatric NMO cohort's clinical, MRI, outcome, and prog

155 oux-en-Y gastric bypass at three specialised paediatric obesity treatment centres in Sweden.

156 ssociates (kappa=0.83, 95% CI 0.60-1.00) and paediatric oncologists (0.84, 0.63-1.00).

157 ications by clinical research associates and paediatric oncologists was almost perfect (0.92, 0.78-1.

158 by two clinical research associates and two paediatric oncologists.

159 ment planning under International Society of Paediatric Oncology (SIOP) protocols is based on staging

160 ren's Oncology Group, the German Society for Paediatric Oncology and Haematology, and the Japanese St

161 defined PPC and called for its inclusion in paediatric oncology care, rigorous investigation has pro

162 perm banking is not universally practised in paediatric oncology centres, and very few adolescent-fri

163 , we report the main ethical developments in paediatric oncology clinical trials from 2003-13.

164 ndependent dataset, International Society of Paediatric Oncology European Neuroblastoma/High-Risk Neu

165 of Norway, Scandinavian Sarcoma Group, Swiss Paediatric Oncology Group, Cancer Research UK, National

166 reported only the incidence or prevalence of paediatric-onset inflammatory bowel disease (diagnosis a

167 Paediatric-onset MS and patients with clinically isolate

168 h decreased time to relapse in patients with paediatric-onset MS.

169 rogressive loss of white matter integrity in paediatric-onset multiple sclerosis, but also show that

170 syndromes eventually received a diagnosis of paediatric-onset multiple sclerosis.

171 sex) did not affect participation in either paediatric or adult studies.

172 munisation centres (3.3%, 95% CI 0-6.9), and paediatric outpatient settings (2.7%, 95% CI 0.3-5.2).

173 key contexts (paediatric inpatient settings, paediatric outpatient settings, nutrition centres, and e

174 duce inappropriate antibiotic prescribing in paediatric outpatients by targeting providers and caregi

175 four contemporary prospective registries of paediatric PAH representing 53 centres in 19 countries.

176 Paediatric palliative care (PPC) endeavours to alleviate

177 ring white matter in 505 serial scans of 132 paediatric participants with acquired demyelinating synd

178 of diffusion parameters compared to healthy paediatric participants, as did patients with non-acute

179 In the healthy paediatric participants, our data demonstrate the expect

180 al presentation, and 106 scans of 80 healthy paediatric participants.

181 ticipation across studies was more than 70% (paediatric participation was 72% and adult participation

182 ived cancer cell line, CLF-PED-015-T, from a paediatric patient with a rare undifferentiated sarcoma.

183 Paediatric patients (<18 years) were identified via ICD

184 xtracted data from the ECDC database for all paediatric patients (age 0-18 years).

185 g (n=141, n=173) and in a cohort with mainly paediatric patients (n=89).

186 Paediatric patients aged 1-17 years who had chronic immu

187 9 centres in the USA and Canada and included paediatric patients aged 4-17 years who were newly diagn

188 mination of DBS finger-prick samples from 47 paediatric patients and results confirmed with concentra

189 py in adults, but its efficacy and safety in paediatric patients are unknown.

190 chemotherapy-induced nausea and vomiting in paediatric patients being treated with moderately or hig

191 nd rapid tool to rule out CD in primary care paediatric patients having CD-related symptoms and IgAD.

192 amined the occurrence of ocular signs in 232 paediatric patients in the Fabry Outcome Survey (FOS) in

193 Magnetic resonance imaging (MRI) in paediatric patients requires them to be calm during the

194 een the gut microbiota and host in new-onset paediatric patients to evaluate causality and mechanisms

195 amples from 10 countries from both adult and paediatric patients were included in the analysis.

196 rly-stage and thorough genetic assessment in paediatric patients with a common variable immunodeficie

197 ter define the state of knowledge on IFDs in paediatric patients with cancer and allogeneic HSCT and

198 portant causes of morbidity and mortality in paediatric patients with cancer and those who have had a

199 , solid food-based diets (SFDs) expressed by paediatric patients with CD, previously treated with EEN

200 ort the usefulness of risk stratification of paediatric patients with Crohn's disease at diagnosis, a

201 INTERPRETATION: In paediatric patients with desmoid-type fibromatosis, the

202 rapy (in the case of tumour progression)-for paediatric patients with desmoid-type fibromatosis.

203 e efficacious and safe dose of ivabradine in paediatric patients with dilated cardiomyopathy and symp

204 e disease as indicated by FOS-MSSI scores in paediatric patients with Fabry disease.

205 res that were routinely taken from adult and paediatric patients with fever or suspicion of sepsis ad

206 and clinical response to thiopurine drugs in paediatric patients with inflammatory bowel disease.

207 tial diagnostic evaluation of both adult and paediatric patients with multiple sclerosis.

208 re and cellular reactivity against myelin in paediatric patients with multiple sclerosis.

209 did a prospective inception cohort study of paediatric patients with newly diagnosed Crohn's disease

210 nd safety of dexamethasone (DEX) implants in paediatric patients with noninfectious intermediate or p

211 usion protein (rFIXFc) in previously treated paediatric patients younger than 12 years with severe ha

212 esponse and organ damage--mainly reported in paediatric patients, but reports of adult presentation a

213 eria, including 1403 adult patients and 1937 paediatric patients.

214 ty p=0.003, and k-core p=0.007), but not for paediatric patients.

215 no large randomised trials are available for paediatric patients.

216 e satellite cells following a burn injury in paediatric patients.

217 significant in adults (p<0.0001), but not in paediatric patients.

218 or examinations of obese, claustrophobic and paediatric patients.The aim of our study was to compare

219 terms used were: postoperative pain; nurs*; paediatrics; pediatrics; children; pain assessment; non-

220 k (CM) allergy (CMA) affects up to 3% of the paediatric population and recent data suggest that only

221 onfirms that IOP rises may also occur in the paediatric population and should be monitored and treate

222 disease and to identify risk factors in the paediatric population are hampered by inadequate mandato

223 Studies regarding the paediatric population were excluded, as were studies des

224 al measurements and for home use even in the paediatric population.

225 re higher than those reported in the general paediatric population.

226 ome could contribute to liver disease in the paediatric population.

227 AND (incidence OR prevalence)." We excluded paediatric populations (aged younger than 18 years) and

228 and support consideration of lower doses for paediatric populations and those who request boosting.

229 n studies in a diverse range of settings and paediatric populations are warranted.

230 y a few of the management strategies used in paediatric populations have been tested in randomised co

231 HIV testing in paediatric populations in low-income and middle-income c

232 panded programme on immunisation centres) in paediatric populations in low-income and middle-income c

233 us unusual tremor syndromes in the adult and paediatric populations.

234 ribed epinephrine auto-injectors (EAI) among paediatric populations.

235 n 1990 and 2012 exploring registered nurses' paediatric postoperative pain management practices were

236 (Innovative Therapy for Children with Cancer Paediatric Preclinical Proof-of-Concept Platform); paedi

237 to guide antipsychotic treatment choices for paediatric psychosis are urgently needed because extrapo

238 Such a novel manifestation of paediatric RCC has not been described previously in lite

239 The aggressive biological behaviour of the paediatric RCC in our case and the consequent atypical i

240 tidisciplinary teams, orthopaedics, cardiac, paediatric, reconstructive, obstetric fistula, neurosurg

241 tidisciplinary teams, orthopaedics, cardiac, paediatric, reconstructive, obstetric fistula, neurosurg

242 Historically, the practice of paediatric regional anesthesia was based largely on info

243 The European Paediatric Regulation facilitates paediatric class waive

244 e suppression of article 11b of the European Paediatric Regulation, which allows product-specific wai

245 Paediatric renal cell carcinoma (RCC) is a rare neoplasm

246 , Lung Foundation Netherlands, International Paediatric Research Foundation, Maastricht University, C

247 re; four experts of the European Society for Paediatric Research; two independent experts from the US

248 219 patients with paediatric RRMS or CIS were enrolled.

249 n 1 or 2 and the Charcot-Marie-Tooth disease paediatric scale outcome instruments.

250 To capture the complexity and diversity of paediatric solid tumours and establish new models of rec

251 Paediatric solid tumours arise from endodermal, ectoderm

252 ut recent literature contains information on paediatric specific risks and benefits of old and new te

253 Paediatric-specific rehabilitation techniques were appli

254 n-invasively using flow cytometry to analyse paediatric sputum samples.

255 tric Preclinical Proof-of-Concept Platform); paediatric strategy forums; and the suppression of artic

256 e was assessed during a home-visit using the Paediatric Stroke Outcome Measure (PSOM).

257 ressions of recovery were assessed using the Paediatric Stroke Recurrence and Recovery Questionnaire

258 searched MEDLINE, Embase, and PsycInfo, for paediatric studies published in 2010-15 and adults studi

259 In paediatric studies, recruitment of participants at diagn

260 specialists in allergology or tertiary care paediatric subspecialists in allergy.

261 randomised controlled study at 19 specialist paediatric surgery centres, 17 of which were in the UK,

262 -2014) was undertaken through the Australian Paediatric Surveillance Unit, with monthly notification

263 vir as dual or triple fixed-dose-combination paediatric tablets with lamivudine and nevirapine or efa

264 ms of action were then assessed as potential paediatric therapeutic targets by both a literature sear

265 atment are needed during the transition from paediatric to adult endocrine care, and during pregnancy

266 ust, 2012, and January, 2015, 1018 difficult paediatric tracheal intubation encounters were done.

267 andidates <50%, mean 49% [95% CI 45-52]) and paediatric trauma (212 pre-course to 161 post-course can

268 to 76%, p<0.05) particularly struggled with paediatric trauma (94 candidates <50%, mean 24.23 [95% C

269 weakness unique to each cadre, particularly paediatric trauma care.

270 ment, chest injuries, major haemorrhage, and paediatric trauma.

271 her explored, as this knowledge could inform paediatric treatment decisions.

272 Only 13 (35.1%) had the classical paediatric triad of abdominal pain, a palpable abdominal

273 arability with field trials and specifics of paediatric trials and regulatory issues.

274 No paediatric trials have compared nucleoside reverse-trans

275 e estimated that 39 000 (17%, 23 000-73 000) paediatric tuberculosis deaths worldwide were in childre

276 count for 27% (22-33) of the total burden of paediatric tuberculosis in the 22 countries.

277 treatment estimates to disaggregate the WHO paediatric tuberculosis incidence estimates by age, HIV,

278 Our model has shown that the incidence of paediatric tuberculosis is higher than the number of not

279 s disease, no age-disaggregated estimates of paediatric tuberculosis mortality exist, and tuberculosi

280 We used paediatric tuberculosis notification data and HIV and an

281 Neuroblastoma is a malignant paediatric tumour of the sympathetic nervous system.

282 largest dataset ever assembled for this rare paediatric tumour.

283 largest dataset ever assembled for this rare paediatric tumour.

284 our drug targets; molecular profiling of all paediatric tumours at diagnosis and relapse; a joint aca

285 pigenetic regulatory proteins, in over 1,000 paediatric tumours to define the landscape of somatic mu

286 's disease (CD) and for 8 SNPs in 5 genes of paediatric ulcerative colitis (UC).

287 Previous retrospective studies of paediatric ulcerative colitis have had limited ability t

288 e of 4-15 years, referred to a tertiary care paediatric unit, North Colombo Teaching Hospital Ragama,

289 e hospital, mainly (60.0%) referred from the paediatric unit, with slightly over one third (36.2%) of

290 t advances in the surgical management of six paediatric urological disorders.

291 Paediatric urological surgery is often required for mana

292 ansetron was dosed per the product label for paediatric use or local standard of care.

293 ation programme under the new policy of mass paediatric vaccination in England.

294 me cost-effectiveness in the presence of the paediatric vaccination programme is needed.

295 ts suggest that well timed administration of paediatric vaccination would reduce the number of low-ri

296 needed to support broader implementation of paediatric vascular composite allotransplantation.

297 Long-term trends in paediatric viral meningitis in England have not previous

298 ssions for acute gastroenteritis captured in paediatric ward registries decreased by 48-49%, and admi

299 itionally, we reviewed the registries in the paediatric wards at six hospitals from 2009 to 2014 and

300 demonstrable reductions in the incidence of paediatric wheezing/asthma or RTIs following introductio