Ultrasound biomicroscopy evaluation of anterior extension in retinoblastoma: a clinicopathological study.

BACKGROUND: Extension of retinoblastoma cells into the posterior chamber is a criterion for group E according to the international classification of intraocular retinoblastoma. Currently, the anterior extension of retinoblastoma is based on the presence of tumour cells in the anterior chamber assessed by biomicroscopy. AIM: To determine the value of ultrasound biomicroscopy (UBM) in the assessment of posterior chamber involvement in advanced retinoblastoma. METHODS: Retrospective review of all retinoblastoma cases enucleated at the Jules Gonin Eye Hospital from January 1996 to December 2009 for which UBM (35 MHz) evaluation was available. The patients' records were reviewed for patient and tumour features and histopathological findings. UBM findings were compared with histopathological features. RESULTS: UBM documentation was available in 31 cases. Retinoblastoma was detected by UBM in the posterior chamber in 18 cases and was absent in 13 cases while histopathological analysis demonstrated its presence in the posterior chamber in 22 cases and its absence in 9 cases. Among the 18 UBM-positive cases, 7 had biomicroscopic detectable involvement of the anterior chamber. There was a significant correlation between echodensities consistent with retinoblastoma on UBM in the posterior chamber and histopathological tumorous involvement of the posterior chamber (p=0.0001). The sensitivity of UBM in the assessment of posterior chamber invasion by retinoblastoma was 81% and the specificity was 100%. CONCLUSION: In selected cases of advanced retinoblastoma, UBM appears to represent a valuable tool in the precise evaluation of anterior extension of disease, with good sensitivity and specificity for the assessment of posterior chamber involvement. UBM may provide useful criteria governing the indication for enucleation.

National character does not reflect mean personality trait levels in 49 cultures

Most people hold beliefs about personality characteristics typical members of their own and others' cultures. These perceptions of national character may be generalizations from personal experience, stereotypes with a "kernel of truth", or inaccurate stereotypes. We obtained national character ratings of 3989 people from 49 cultures and compared them with the average personality scores of culture members assessed by observer ratings and self-reports. National character ratings were reliable but did not converge with assessed traits. Perceptions of national character thus appear to be unfounded stereotypes that may serve the function of maintaining a national identity.

A new training set-up for trans-apical aortic valve replacement.

Trans-apical aortic valve replacement (AVR) is a new and rapidly growing therapy. However, there are only few training opportunities. The objective of our work is to build an appropriate artificial model of the heart that can replace the use of animals for surgical training in trans-apical AVR procedures. To reduce the necessity for fluoroscopy, we pursued the goal of building a translucent model of the heart that has nature-like dimensions. A simplified 3D model of a human heart with its aortic root was created in silico using the SolidWorks Computer-Aided Design (CAD) program. This heart model was printed using a rapid prototyping system developed by the Fab@Home project and dip-coated two times with dispersion silicone. The translucency of the heart model allows the perception of the deployment area of the valved-stent without using heavy imaging support. The final model was then placed in a human manikin for surgical training on trans-apical AVR procedure. Trans-apical AVR with all the necessary steps (puncture, wiring, catheterization, ballooning etc.) can be realized repeatedly in this setting.

Freedom Trial First-Year Extension: Results from 4 Years of Denosumab Exposure in Women with Postmenopausal Osteoporosis

Aims: To investigate the long-term efficacy and safety of denosumab (DMAb) for the treatment of postmenopausal women with osteoporosis in an open-label extension to the 3-year FREEDOM study.1Methods: All women who completed the FREEDOM study were eligible to enter a long-term open-label extension (up to 10 years). After providing informed consent, participants received 6-monthly subcutaneous injections of DMAb (60 mg). Here we report data from the first year of followup. For women randomized to DMAb in the FREEDOM study ('long-term group'), this represents up to 48 months of DMAb exposure (eight 6-monthly injections). For those randomized to placebo ('de novo group') the data are from up to 12 months of exposure (two injections). All participants continued to take calcium (1 g) and vitamin D (≥400 IU) supplements daily. Changes in bone mineral density (BMD) and bone turnover markers (BTM) are reported for subjects enrolled in the extension. No formal statistical testing was planned for this interim report. P-values are descriptive.Results: Overall, 4,550 eligible women (70.2%) who completed the FREEDOM study entered the open-label extension study (long-term, n=2,343; de novo, n=2,207). During the first year of the extension, lumbar spine (LS) BMD in the long-term group further increased by 2.0% (12.1% increase vs. FREEDOM baseline at 48 months), and total hip (TH) BMD further increased by 0.8% (6.5% increase at 48 months) (p<0.0001 for both BMD gains during year 4; Fig. 1). During the first year of the extension, LS and TH BMD increased by 5.4% and 3.0%, respectively in the de novo group (both p<0.0001). After DMAb initiation, serum C-telopeptide (CTX) in the de novo group decreased rapidly and similarly to the long-term group (Fig. 2). Reductions in BTMs continue to attenuate at the end of the dosing interval as previously reported. Adverse event (AE) rates were similar (70.4% of women in the longterm group and 67.9% in the de novo group). Serious Aes were also similar (9.8% and 11.2% of women, respectively). During year 4, osteoporotic nonvertebral fractures were reported in 31 women in the long-term group and 51 in the denovo group.Fig. 1. Percentage change in BMD with denosumab for4 years (long-term) or 1 year (de novo)Fig. 2. Percentage change in sCTX over timeConclusions: These interim results suggest that continuation of DMAb treatment through 48 months is associated with further significant increases in spine and hip BMD with sustained reduction of bone turnover. The de-novo treatment group results confirm the first year active treatment findings previously reported1.Acknowledgements: Amgen Inc. sponsored this study. Figure ©2010, American Society for Bone and Mineral Research, used by permission, all rights reserved. Disclosure of Interest: H. Bone Grant/Research Support from: Amgen, Eli Lilly, Merck, Nordic Bioscience, Novartis, Takeda Pharmaceuticals, Consultant/Speaker's bureau/ Advisory activities with: Amgen, Merck, Takeda Pharmaceuticals, Zelos, S. Papapoulos Consultant/Speaker's bureau/ Advisory activities with: Amgen, Merck, Novartis, Lilly, Procter and Gamble, GSK, M.-L. Brandi Grant/Research Support from: MSD, GSK, Nycomed, NPS, Amgen, J. Brown Grant/Research Support from: Abbott, Amgen, Bristol Myers Squibb, Eli Lilly, Pfizer, Roche, Consultant/ Speaker's bureau/Advisory activities with: Abbott, Amgen, Eli Lilly, Novartis, Merck, Warner Chilcott,, R. Chapurlat Grant/Research Support from: Servier, Sanofi-Aventis, Warner-Chilcott, Novartis, Merck, Consultant/Speaker's bureau/Advisory activities with: Servier, Novartis, Amgen, E. Czerwinski: None Declared, N. Daizadeh Employee of: Amgen Inc., Stock ownership or royalties of: Amgen Inc., A. Grauer Employee of: Amgen Inc., Stock ownership or royalties of: Amgen Inc., C. Haller Employee of: Amgen Inc., Stock ownership or royalties of: Amgen Inc., M.-A. Krieg: None Declared, C. Libanati Employee of: Amgen Inc., Stock ownership or royalties of: Amgen Inc., Z. Man Grant/Research Support from: Amgen, D. Mellström: None Declared, S. Radominski Grant/Research Support from: Amgen, Pfizer, Roche, BMS, J.-Y. Reginster Grant/Research Support from: Bristol Myers Squibb, Merck Sharp & Dohme, Rottapharm, Teva, Lilly, Novartis, Roche, GlaxoSmithKline, Amgen, Servier, Consultant/Speaker's bureau/ Advisory activities with: Servier, Novartis, Negma, Lilly,Wyeth, Amgen, GlaxoSmithKline, Roche, Merckle, Nycomed, NPS, Theramex, UCB, Merck, Sharpe & Dohme, Rottapharm, IBSA, Genvrier, Teijin, Teva, Ebewee Pharma, Zodiac, Analis, Theramex, Novo-Nordisk, H. Resch: None Declared, J. A. Román Grant/Research Support from: Roche, Pharma, C. Roux Grant/Research Support from: Amgen, MSD, Novartis, Servier, Roche, Consultant/ Speaker's bureau/Advisory activities with: Amgen, MSD, Novartis, Servier, Roche, S. Cummings Grant/ Research Support from: Amgen, Lilly, Consultant/Speaker's bureau/Advisory activities with: Amgen, Lilly, Novartis, Merck

Synorogenic extension in the Tethyan Himalaya documented by structural studies and the Kubler index, Lachung La area, NW India

Tectonic observations in the Tethyan Himalaya reveal an important extensional event that succeeds the emplacement of SW-verging nappes. A major thrust, called the Kum Tso Thrust, has been backfolded and reactivated by normal faulting associated with this event. Measurements of the Kubler index, coupled with characterization of clay-size paragenesis show the effect of normal faulting on the regional metamorphic zonation and indicate that important extension zones, like the Sarchu-Lachung La Normal Fault Zone (SLFZ), exist within the Tethyan Himalaya. Diagenetic limestones from within the SLFZ are characterized by the occurrence of mixed-layered clay phases, kaolinite and an illite with a 001 peak >0.4 Delta degrees2 theta. This zone is bordered by two anchizonal-to-epizonal zones, where illite peaks become narrower. Further to the NE the successive appearance of biotite, chloritoid, garnet and garnet-staurolite-kyanite assemblapes testifies to an increase in metamorphic grade. The cataclastic samples from the normal faults contain kaolinite, smectite and a `broad' illite, indicating that extension occurs under diagenetic conditions.

Phylogenetic approach reveals that virus genotype largely determines HIV set-point viral load.

HIV virulence, i.e. the time of progression to AIDS, varies greatly among patients. As for other rapidly evolving pathogens of humans, it is difficult to know if this variance is controlled by the genotype of the host or that of the virus because the transmission chain is usually unknown. We apply the phylogenetic comparative approach (PCA) to estimate the heritability of a trait from one infection to the next, which indicates the control of the virus genotype over this trait. The idea is to use viral RNA sequences obtained from patients infected by HIV-1 subtype B to build a phylogeny, which approximately reflects the transmission chain. Heritability is measured statistically as the propensity for patients close in the phylogeny to exhibit similar infection trait values. The approach reveals that up to half of the variance in set-point viral load, a trait associated with virulence, can be heritable. Our estimate is significant and robust to noise in the phylogeny. We also check for the consistency of our approach by showing that a trait related to drug resistance is almost entirely heritable. Finally, we show the importance of taking into account the transmission chain when estimating correlations between infection traits. The fact that HIV virulence is, at least partially, heritable from one infection to the next has clinical and epidemiological implications. The difference between earlier studies and ours comes from the quality of our dataset and from the power of the PCA, which can be applied to large datasets and accounts for within-host evolution. The PCA opens new perspectives for approaches linking clinical data and evolutionary biology because it can be extended to study other traits or other infectious diseases.