ObjectiveThe Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH).ParticipantsA closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrinologists, basic scientists, regulatory scientists, and participants from the pharmaceutical industry.EvidenceCurrent literature was reviewed for gaps in knowledge. Expert opinion was used to suggest studies required to address potential safety and efficacy issues.Consensus processFollowing plenary presentations summarizing the literature, breakout groups discussed questions framed by the planning committee. Attendees reconvened after each breakout session to share group reports. A writing team compiled the breakout session reports into a draft document that was discussed and revised in an open forum on the concluding day. This was edited further and then circulated to attendees from academic institutions for review after the meeting. Participants from pharmaceutical companies did not participate in the planning, writing, or in the discussions and text revision on the final day of the workshop. Scientists from industry and regulatory agencies reviewed the manuscript to identify any factual errors.ConclusionsLAGH compounds may represent an advance over daily GH injections because of increased convenience and differing phamacodynamic properties, providing the potential for improved adherence and outcomes. Better methods to assess adherence must be developed and validated. Long-term surveillance registries that include assessment of efficacy, cost-benefit, disease burden, quality of life, and safety are essential for understanding the impact of sustained exposure to LAGH preparations.

SummaryThe aim of this six-centre, split-sample study was to compare ThinPrep fluid-based cytology to the conventional Papanicolaou smear. Six cytopathology laboratories and 35 gynaecologists participated. 5428 patients met the inclusion criteria (age > 18 years old, intact cervix, informed consent). Each cervical sample was used first to prepare a conventional Pap smear, then the sampling device was rinsed into a PreservCyt vial, and a ThinPrep slide was made. Screening of slide pairs was blinded (n = 5428). All non-negative concordant cases (n = 101), all non-concordant cases (n = 206), and a 5% random sample of concordant negative cases (n = 272) underwent review by one independent pathologist then by the panel of 6 investigators. Initial (blinded) screening results for ThinPrep and conventional smears were correlated. Initial diagnoses were correlated with consensus cytological diagnoses. Differences in disease detection were evaluated using McNemar's test. On initial screening, 29% more ASCUS cases and 39% more low-grade squamous intraepithelial lesions (LSIL) and more severe lesions (LSIL+) were detected on the ThinPrep slides than on the conventional smears (P = 0.001), including 50% more LSIL and 18% more high-grade SIL (HSIL). The ASCUS:SIL ratio was lower for the ThinPrep method (115:132 = 0.87:1) than for the conventional smear method (89:94 = 0.95:1). The same trend was observed for the ASCUS/AGUS:LSIL ratio. Independent and consensus review confirmed 145 LSIL+ diagnoses; of these, 18% more had been detected initially on the ThinPrep slides than on the conventional smears (P = 0.041 360-366 © 2001 Cancer Research Campaign doi: 10.1054/ bjoc.2000.1588, available online at http://www.idealibrary.com on http://www.bjcancer.com Linder and Zahniser, 1997;Roberts et al, 1997; Bolick and Heuman, 1998;Corkill et al, 1998;Dupree et al, 1998;Papillo et al, 1998; Carpenter and Daveu, 1999;Diaz-Rosario and Kabawat, 1999;Guidos and Selvaggi, 1999;Wang et al, 1999; Yeoh et al, 1999; Weintraub and Morabia, 2000).This study, conducted in France, is the first formal multilaboratory, large-scale evaluation of the ThinPrep Pap Test in the European setting. METHODS Study organization6 laboratories in France participated in the study, each laboratory obtaining cervical samples from 5 to 8 participating gynaecologists and their patients. A total of 35 gynaecologists participated in the study.Before the study commenced, the 6 laboratory directors (4 cytopathologists and 2 cytologists) and their participating staff were trained to interpret ThinPrep slides, and also to use the Bethesda System for reporting the screening results (Kurman and Solomon, 1994). The study protocols and forms were reviewed and approved by the local Ethics Committee.Patients were recruited sequentially in the participating gynaecologists' practices, from March 1998 to September 1998. According to the inclusion criteria, female patients aged 18 and older, attending regular cervical cancer screening, and who voluntarily gave their informed consen...

WHAT'S KNOWN ON THIS SUBJECT: XY disorders of sex development have a diverse etiology and often present with atypical genitalia in the newborn period. Sex assignment in those cases in whom this is marked genital ambiguity is a rare, challenging situation that requires multidisciplinary input. WHAT THIS STUDY ADDS:An international registry has shown temporal changes over the last 3 decades in the practice of sex assignment with a greater proportion of severely affected infants being raised as boys, raising the need for long-term monitoring of these children. abstract BACKGROUND AND OBJECTIVE: It is unclear whether the proportion of infants with a disorder of sex development who are raised as male or female has changed over time. The temporal trends in sex assignment of affected cases entered in the International Disorder of Sex Development (I-DSD) Registry were studied. METHODS:Cases of disorders of sex development reported as partial androgen insensitivity syndrome (PAIS; n = 118), disorder of gonadal development (DGD; n = 232), and disorder of androgen synthesis (DAS; n = 104) were divided into those who were born before 1990, 1990-1999, and after 1999. External appearance of the genitalia was described by the external masculinization score. RESULTS:The median (5th-95th percentile) external masculinization scores of those infants with PAIS, DGD, and DAS who were raised as boys were 6 (2-9), 6 (3-9), and 6 (1-12), respectively, and were significantly higher than in those raised as girls (2 [0-6], 2 [0-7], and 0 [0-5], respectively); this difference was maintained in the 3 temporal birth cohorts (P , .01). Of the 118 cases in the pre-1990 cohort, 41 (35%) were raised as boys; of the 148 cases in the 1990-1999 cohort, 60 (41%) were raised as boys; and of the 188 cases in the post-1999 cohort, 128 (68%) were raised as boys.

BackgroundA co-ordinated tissue-independent gene expression profile associated with growth is present in rodent models and this is hypothesised to extend to all mammals. Growth in humans has similarities to other mammals but the return to active long bone growth in the pubertal growth spurt is a distinctly human growth event. The aim of this study was to describe gene expression and biological pathways associated with stages of growth in children and to assess tissue-independent expression patterns in relation to human growth.ResultsWe conducted gene expression analysis on a library of datasets from normal children with age annotation, collated from the NCBI Gene Expression Omnibus (GEO) and EBI Arrayexpress databases. A primary data set was generated using cells of lymphoid origin from normal children; the expression of 688 genes (ANOVA false discovery rate modified p-value, q < 0.1) was associated with age, and subsets of these genes formed clusters that correlated with the phases of growth – infancy, childhood, puberty and final height. Network analysis on these clusters identified evolutionarily conserved growth pathways (NOTCH, VEGF, TGFB, WNT and glucocorticoid receptor – Hyper-geometric test, q < 0.05). The greatest degree of network ‘connectivity’ and hence functional significance was present in infancy (Wilcoxon test, p < 0.05), which then decreased through to adulthood. These observations were confirmed in a separate validation data set from lymphoid tissue. Similar biological pathways were observed to be associated with development-related gene expression in other tissues (conjunctival epithelia, temporal lobe brain tissue and bone marrow) suggesting the existence of a tissue-independent genetic program for human growth and maturation.ConclusionsSimilar evolutionarily conserved pathways have been associated with gene expression and child growth in multiple tissues. These expression profiles associate with the developmental phases of growth including the return to active long bone growth in puberty, a distinctly human event. These observations also have direct medical relevance to pathological changes that induce disease in children. Taking into account development-dependent gene expression profiles for normal children will be key to the appropriate selection of genes and pathways as potential biomarkers of disease or as drug targets.

ObjectiveIndividual sensitivity to recombinant human GH (r-hGH) is variable. Identification of genetic factors contributing to this variability has potential use for individualization of treatment. The objective of this study was to identify genetic markers and gene expression profiles associated with growth response on r-hGH therapy in treatment-naïve, prepubertal children with GH deficiency (GHD) or Turner syndrome (TS).DesignA prospective, multicenter, international, open-label pharmacogenomic study.MethodsThe associations of genotypes in 103 growth- and metabolism-related genes and baseline gene expression profiles with growth response to r-hGH (cm/year) over the first year were evaluated. Genotype associations were assessed with growth response as a continuous variable and as a categorical variable divided into quartiles.ResultsEleven genes in GHD and ten in TS, with two overlapping between conditions, were significantly associated with growth response either as a continuous variable (seven in GHD, two in TS) or as a categorical variable (four more in GHD, eight more in TS). For example, in GHD, GRB10 was associated with high response (≥Q3; P=0.0012), while SOS2 was associated with low response (≤Q1; P=0.006), while in TS, LHX4 was associated with high response (P=0.0003) and PTPN1 with low response (P=0.0037). Differences in expression were identified for one of the growth response-associated genes in GHD (AKT1) and for two in TS (KRAS and MYOD1).ConclusionsCarriage of specific growth-related genetic markers is associated with growth response in GHD and TS. These findings indicate that pharmacogenomics could have a role in individualized management of childhood growth disorders.

We studied short- and long-term responses to growth hormone (GH) treatment and adverse medical events (AE) in 488 patients with craniopharyngioma who were entered into the Kabi International Growth Study (KIGS). First-year growth response and responsiveness (n = 394) were similar to those seen in children with idiopathic GH deficiency. The growth response over 5 years (n = 152) was unaffected by the recurrence of tumour and prior tumour management, but was greater in those receiving thyroxine. Mean height standard deviation scores (SDS) at the end of GH treatment (n = 129) was –0.7 ± 1.2, and 79% achieved a height over –2 SD of target height, with evidence of further growth potential. Final height SDS correlated positively with height SDS at the start of treatment and with target height SDS, whereas gain in height SDS was inversely correlated with height SDS and bone age at the start of GH treatment. The rate of recurrence of tumour, 0.045/treatment year, was greater in those who had been treated with surgery alone compared to surgery and cranial irradiation. Other AE included headaches, fluid retention and convulsions occurring at rates of 0.025, 0.005 and 0.004/treatment year, respectively. We concluded that GH treatment is safe and effective in children with craniopharyngioma and provide data for counselling of parents about outcome during GH treatment.

Twenty patients with a chronic total coronary artery occlusion were studied before and 1 to 48 months (mean 9) after successful recanalization by angioplasty and compared with a group of 20 normal subjects. Before angioplasty, 19 of these 20 patients had angina. Collateral vessels to the distal part of the occluded vessel were visible in all 20 patients. A previous myocardial infarction was documented in 14 patients (9 with a Q wave and 5 with a non-Q wave infarction). At the time of follow-up, three patients were symptomatic: one had unstable angina and two had a positive stress test. The follow-up angiogram showed a significant restenosis in six patients and reocclusion in two. The mean ejection fraction had improved slightly from 59 +/- 11% to 63 +/- 9% (p less than 0.05). Left ventricular wall motion synchronism was studied using two variables for 128 shortening segments: the "time of peak contraction" and the "time of peak relaxation," as obtained from biharmonic Fourier transformation for each segment. Their respective standard deviations reflect the synchronism of contraction and relaxation. The mean standard deviations of the two variables expressed in degrees of one cardiac cycle (360 degrees) were respectively: 5.5 +/- 0.4 degrees for the time of peak contraction and 6.0 +/- 0.5 degrees for the time of peak relaxation in the 20 normal subjects, 11.7 +/- 1.7 degrees and 23.0 +/- 3.0 degrees before recanalization and 9.6 +/- 1.8 degrees and 12.5 +/- 2.2 degrees at follow-up in the group of 20 patients. These values were significantly higher (p less than 0.05) in the patients than in the normal group.(ABSTRACT TRUNCATED AT 250 WORDS)

To cite this version:Pierre Chatelain, Alexandre Krupa, Maud Marchal. Real-time needle detection and tracking using a visually servoed 3D ultrasound probe. IEEE Int. Conf. on Robotics and Automation, ICRA'13, May 2013, Karlsruhe, Germany. pp.1668-1673, 2013 Real-time needle detection and tracking using a visually servoed 3D ultrasound probePierre Chatelain, Alexandre Krupa and Maud MarchalAbstract-In this paper, we present a method to localize and track manually inserted needles in real-time using a threedimensional ultrasound probe mounted on a robotized arm. The system tracks the needle using online image processing. We first propose a new algorithm capable of robustly detecting a needle from the moment it is inserted, without any a priori information on the insertion direction. By combining the random sample consensus (RANSAC) algorithm with Kalman filtering in closed loop, we achieve robust real-time tracking of the needle. In addition, we propose a control scheme to automatically guide the ultrasonic probe in order to keep the needle within the field of view, while aligning its axis with the ultrasound beam. This method will ease the insertion of the needle by the operator, and allow the development of autonomous needle insertion by medical robots.