Gonadotrophin stimulation for in vitro fertilization significantly alters the hormone milieu in follicular fluid: a comparative study between natural cycle IVF and conventional IVF.

STUDY QUESTION Is the steroid hormone profile in follicular fluid (FF) at the time of oocyte retrieval different in naturally matured follicles, as in natural cycle IVF (NC-IVF), compared with follicles stimulated with conventional gonadotrophin stimulated IVF (cIVF)? SUMMARY ANSWER Anti-Mullerian hormone (AMH), testosterone (T) and estradiol (E2) concentrations are ∼3-fold higher, androstenedione (A2) is ∼1.5-fold higher and luteinizing hormone (LH) is ∼14-fold higher in NC-IVF than in cIVF follicles, suggesting an alteration of the follicular metabolism in conventional gonadotrophin stimulated IVF. WHAT IS KNOWN ALREADY In conventional IVF, the implantation rate of unselected embryos appears to be lower than in NC-IVF, which is possibly due to negative effects of the stimulation regimen on follicular metabolism. In NC-IVF, the intrafollicular concentration of AMH has been shown to be positively correlated with the oocyte fertilization and implantation rates. Furthermore, androgen treatment seems to improve the ovarian response in low responders. STUDY DESIGN, SIZE, DURATION This cross-sectional study involving 36 NC-IVF and 40 cIVF cycles was performed from 2011 to 2013. Within this population, 13 women each underwent 1 NC-IVF and 1 cIVF cycle. cIVF was performed by controlled ovarian stimulation with HMG and GnRH antagonists. PARTICIPANTS/MATERIALS, SETTING, METHODS Follicular fluid was collected from the leading follicles. AMH, T, A2, dehydroepiandrosterone (DHEA), E2, FSH, LH and progesterone (P) were determined by immunoassays in 76 women. Aromatase activity in follicular fluid cells was analysed by a tritiated water release assay in 33 different women. For statistical analysis, the non-parametric Mann-Whitney U or Wilcoxon tests were used. MAIN RESULTS AND ROLE OF CHANCE In follicular fluid from NC-IVF and from cIVF, median levels were 32.8 and 10.7 pmol/l for AMH (P < 0.0001), 47.2 and 18.8 µmol/l for T (P < 0.0001), 290 and 206 nmol/l for A2 (P = 0.0035), 6.7 and 5.6 pg/ml for DHEA (n.s.), 3292 and 1225 nmol/l for E2 (P < 0.0001), 4.9 and 7.2 mU/ml for FSH (P < 0.05), 14.4 and 0.9 mU/ml for LH (P < 0.0001) and 62 940 and 54 710 nmol/l for P (n.s.), respectively. Significant differences in follicular fluid concentrations for AMH, E2 and LH were also found in the 13 patients who underwent both NC-IVF and cIVF when they were analysed separately in pairs. Hormone analysis in serum excluded any relevant impact of AMH, T, A2, and E2 serum concentration on the follicular fluid hormone concentrations. Median serum concentrations were 29.4 and 0.9 mU/ml for LH (P < 0.0001) and 2.7 and 23.5 nmol/l for P (P < 0.0001) after NC-IVF and c-IVF, respectively. Positive correlations were seen for FF-AMH with FF-T (r = 0.35, P = 0.0002), FF-T with FF-LH (r = 0.48, P < 0.0001) and FF-E2 with FF-T (r = 0.75, P < 0.0001). The analysis of aromatase activity was not different in NC-IVF and cIVF follicular cells. LIMITATION, REASONS FOR CAUTION Any association between the hormone concentrations and the implantation potential of the oocytes could not be investigated as the oocytes in cIVF were not treated individually in the IVF laboratory. Since both c-IVF and NC-IVF follicles were stimulated by hCG before retrieval, the endocrine milieu in the natural cycle does not represent the pure physiological situation. WIDER IMPLICATIONS OF THE FINDINGS The endocrine follicular milieu and the concentration of putative markers of oocyte quality, such as AMH, are significantly different in gonadotrophin-stimulated conventional IVF compared with natural cycle IVF. This could be a cause for the suggested lower oocyte quality in cIVF compared with naturally matured oocytes. The reasons for the reduced AMH concentration might be low serum and follicular fluid LH concentrations due to LH suppression, leading initially to low follicular androgen concentrations and then to low follicular AMH production. STUDY FUNDING/COMPETING INTERESTS Funding for this study was obtained from public universities (for salaries) and private industry (for consumables). Additionally, the study was supported by an unrestricted grant from MSD Merck Sharp & Dohme GmbH and IBSA Institut Biochimique SA. The authors are clinically involved in low-dose monofollicular stimulation and IVF therapies, using gonadotrophins from all gonadotrophin distributors on the Swiss market, including Institut Biochimique SA and MSD Merck Sharp & Dohme GmbH. Otherwise, the authors have no competing interests. TRIAL REGISTRATION NUMBER Not applicable.

Genetic predisposition to prostate cancer

Prostate cancer (PC) is a significant economic and health burden in the U.S. and Europe but its causes are largely unknown. The most significant risk factors (after gender) are age and family history of the disease. A gene with high penetrance but low frequency on chromosome 1q, HPC 1, has been suggested to cause a proportion of the familial aggregation of PC but other more common genes, conferring less risk, are also thought to contribute to disease predisposition. We have pursued a strategy to study both types of genetic risk in PC. To identify high penetrance genes, affected men from thirteen families have been genotyped for genetic linkage analysis at six microsatellite markers spanning 45 cM of 1q24-25. Both LOD score and non-parametric statistics provide no significant support for HPC1 in this genomic region, although 3 of the families did combine to produce a LOD score of 0.9. These families will be included in a genome wide search for other PC predisposition genes as part of a multinational collaboration.^ For study of common genetic factors in PC development, leukocyte DNA samples from an unselected series of 55 patients and 67 controls have been examined for genetic differences in two other candidate genes, the androgen receptor gene, hAR, at Xq11-12, and the vitamin D receptor gene, hVDR, at 12q12-14. hAR was typed for two trinucleotide repeat length polymorphisms, (CAG)$\rm\sb{n}$ and (GGC)$\rm\sb{n},$ encoding polyglutamine and polyglycine tracts, respectively, which have been implicated in PC susceptibility. These data, combined with similarly processed patients and controls from the U.K. show no consistent association of allele length with PC risk. A novel finding, however, has been a significant association between the number of GGC repeats and the length of time between diagnosis and relapse in stage T1-T4 Caucasian patients irrespective of therapy and age of the patient. Of 49 patients who relapsed out of 108 entering the study, those with 16 or fewer GGC repeats had an average relapse-free-period of 101 (+/$-$7.7) months while for those with more than 16 repeats the period averaged 48 (+/$-$2.9) months, a difference of 2.1 fold or 4.4 years.^ The second gene, hVDR, was genotyped at two polymorphisms, a synonymous C/T substitution in exon 9 identified by differential TaqI enzymatic digestion and a variable length polyA tract in the 3$\sp\prime$ UTR. Although these polymorphisms are in strong linkage disequilibrium only the polyA region showed a possible association with PC risk. Men homozygous for alleles with fewer than 18 A's had an increased risk (OR = 3.0, p = 0.0578) compared to controls. This result is opposite to the findings of others and may either indicate off-setting random errors which together balance out to no significant overall effect or reflect more complex genetic and/or environmental associations.^ Overall, this research suggests that single gene familial predisposition may be less prominent in PC than in other cancers and that the characteristics of PC pathology may be useful in identifying the effects of common genetic factors. ^

A nonparametric method of comparing the partial areas under two correlated receiver operating characteristic curves

A non-parametric method was developed and tested to compare the partial areas under two correlated Receiver Operating Characteristic curves. Based on the theory of generalized U-statistics the mathematical formulas have been derived for computing ROC area, and the variance and covariance between the portions of two ROC curves. A practical SAS application also has been developed to facilitate the calculations. The accuracy of the non-parametric method was evaluated by comparing it to other methods. By applying our method to the data from a published ROC analysis of CT image, our results are very close to theirs. A hypothetical example was used to demonstrate the effects of two crossed ROC curves. The two ROC areas are the same. However each portion of the area between two ROC curves were found to be significantly different by the partial ROC curve analysis. For computation of ROC curves with large scales, such as a logistic regression model, we applied our method to the breast cancer study with Medicare claims data. It yielded the same ROC area computation as the SAS Logistic procedure. Our method also provides an alternative to the global summary of ROC area comparison by directly comparing the true-positive rates for two regression models and by determining the range of false-positive values where the models differ. ^

Understanding the underlying mechanisms of recent Jatropha curcas L. adoption by smallholders in Kenya: A rural livelihood assessment in Bondo, Kibwezi, and Kwale districts

Between 2004 and 2007, NGOs, community based organisations and private investors promoted jatropha in Kenya with the aim of generating additional income and producing biofuel for rural development. By 2008 it became gradually evident that jatropha plantations (both mono- and intercropping) are uneconomical and risky due to competition for land and labour with food crops. Cultivation of jatropha hedges was found to have better chances of economic success and to present only little risks for the adopting farmers. Still, after 2008 a number of farmers went on adopting jatropha in plots rather than as hedges. It is hypothesised that lack of awareness about the low economic prospects of jatropha plantations was the main reason for continued adoption, and that smallholder farmers with higher resource endowments mainly ventured into its cultivation. In this study we provide an empirical basis for understanding the role of households' capital assets in taking up new livelihood strategies by smallholder farmers in three rural districts in Kenya. For that purpose, we assess the motivation and enabling factors that led to the adoption of jatropha as a new livelihood strategy, as well as the context in which promotion and adoption took place. A household survey was conducted in 2010, using a structured questionnaire, to collect information on household characteristics and capital asset endowment. Data were analysed using descriptive statistics and non-parametric statistical tests. We established that access to additional income and own energy supply were the main motivation for adoption of jatropha, and that financial capital assets do not necessarily have a positive influence on adoption as hypothesised. Further, we found that the main challenges that adopting farmers faced were lack of access to information on good management practices and lack of a reliable market. We conclude that continued adoption of on-farm jatropha after 2008 is a result of lacking awareness about the low economic value of this production type. We recommend abandoning on-farm production of jatropha until improved seed material and locally adapted agronomic knowledge about jatropha cultivation becomes available and its production becomes economically competitive.

Regression of the inflammatory microenvironment of the peritoneal cavity in women with endometriosis by GnRHa treatment.

OBJECTIVE To investigate the effect of gonadotropin-releasing hormone analogues (GnRHa) on the peritoneal fluid microenvironment in women with endometriosis. STUDY DESIGN Peritoneal fluid was collected from 85 women with severe endometriosis (rAFS stage III and IV) during laparoscopic surgery during the proliferative phase. Prior to surgery clinical data were collected. The concentrations of specific markers for endometriosis in the peritoneal fluid were determined using an ELISA and a comparison between peritoneal fluid markers in women using GnRHa and no hormonal treatment was performed using a non-parametric Mann-Whitney U test. RESULTS The study included peritoneal fluid from 39 patients who had been administered GnRHa (Zoladex(®)) in the three months prior to surgery and 46 from women with no hormonal treatment in this period. Concentrations of IL-8, PAPP-A, glycodelin-A and midkine were significantly reduced in the GnRHa treatment group compared to women receiving no hormonal treatment. RANTES, MCP-1, ENA-78, TNF-α, OPG, IP-10 and defensin showed no significant change between the two groups. CONCLUSIONS GnRHa mediate a significant regression in the inflammatory nature of the peritoneal microenvironment in women with endometriosis.

Cultural diasporas

This study examines the contribution that artists from a non-EU background make towards cultural life and cultural industries in Europe and beyond. In particular, it looks at how such artists form "diasporas" which in turn create networks of cultural exchange inside the EU and with third countries. It provides examples of these activities in three broad diaspora groups of African, Balkan and Turkish background.

Precision of fit of implant-supported screw-retained 10-unit computer-aided-designed and computer-aided-manufactured frameworks made from zirconium dioxide and titanium: an in vitro study

OBJECTIVE To analyze the precision of fit of implant-supported screw-retained computer-aided-designed and computer-aided-manufactured (CAD/CAM) zirconium dioxide (ZrO) frameworks. MATERIALS AND METHODS Computer-aided-designed and computer-aided-manufactured ZrO frameworks (NobelProcera) for a screw-retained 10-unit implant-supported reconstruction on six implants (FDI positions 15, 13, 11, 21, 23, 25) were fabricated using a laser (ZrO-L, N = 6) and a mechanical scanner (ZrO-M, N = 5) for digitizing the implant platform and the cuspid-supporting framework resin pattern. Laser-scanned CAD/CAM titanium (TIT-L, N = 6) and cast CoCrW-alloy frameworks (Cast, N = 5) fabricated on the same model and designed similar to the ZrO frameworks were the control. The one-screw test (implant 25 screw-retained) was applied to assess the vertical microgap between implant and framework platform with a scanning electron microscope. The mean microgap was calculated from approximal and buccal values. Statistical comparison was performed with non-parametric tests. RESULTS No statistically significant pairwise difference was observed between the relative effects of vertical microgap between ZrO-L (median 14 μm; 95% CI 10-26 μm), ZrO-M (18 μm; 12-27 μm) and TIT-L (15 μm; 6-18 μm), whereas the values of Cast (236 μm; 181-301 μm) were significantly higher (P < 0.001) than the three CAD/CAM groups. A monotonous trend of increasing values from implant 23 to 15 was observed in all groups (ZrO-L, ZrO-M and Cast P < 0.001, TIT-L P = 0.044). CONCLUSIONS Optical and tactile scanners with CAD/CAM technology allow for the fabrication of highly accurate long-span screw-retained ZrO implant-reconstructions. Titanium frameworks showed the most consistent precision. Fit of the cast alloy frameworks was clinically inacceptable.

Combined effect of a fluoride-, stannous- and chitosan-containing toothpaste and stannous-containing rinse on the prevention of initial enamel erosion-abrasion.

OBJECTIVES The aim of this study was to assess the preventive effect of a fluoride-, stannous- and chitosan-containing (F/Sn/chitosan-) toothpaste (TP) on initial enamel erosion and abrasion. METHODS In total, 150 human premolar enamel specimens were ground, polished and divided into 5 toothpaste/rinse groups (n=30): (G1) placebo-TP/tap water, (G2) sodium fluoride (NaF-) TP/tap water, (G3) F/Sn/chitosan-TP/tap water, (G4) F/Sn/chitosan-TP/Sn-rinse, (G5) NaF-TP/NaF-rinse. The 8-day erosion-abrasion cyclic treatment (one cycle/day) consisted of incubating the samples in artificial saliva (30min), then submitting the samples to toothbrush abrasion (2min incubation in toothpaste slurry; brushing with 20 toothbrush strokes) and rinsing (2min; 10ml) with the respective solution: tap water (G1-G3), Sn-rinse (G4) or NaF-rinse (G5). Afterwards, the samples were submitted to erosion (2min; 30ml 1% citric acid, pH=3.6). Surface microhardness (SMH) was measured initially and after every abrasion and erosion treatment. Enamel substance loss was calculated after each abrasion. Non-parametric ANOVA followed by Wilcoxon rank tests were used for analysis. RESULTS G1 presented the greatest SMH decrease, while G4 presented the least SMH decrease (p<0.001). G3 had a similar SMH decrease to G2 and G5. Substance loss was significantly lower in G4 than all other groups (p<0.05), closely followed by G3. Both G2 and G5 showed similar calculated enamel substance loss to G1. CONCLUSION The treatment with F/Sn/chitosan-TP and tap water provided a similar SMH decrease to both NaF-TP groups, but significantly lower substance loss. F/Sn/Chitosan-TP and Sn-rinse showed a better preventive effect, which promoted less SMH decrease and reduced substance loss. CLINICAL SIGNIFICANCE The toothpaste containing fluoride, stannous and chitosan shows promising results in reducing substance loss from erosion and abrasion. The combination of this toothpaste with the stannous-containing rinse showed even better prevention against erosion-abrasion.

Career adaptability development in adolescence: Multiple prdictors and effect on sense of power and life satisfaction

This longitudinal panel study investigated predictors of career adaptability development and its effect on development of sense of power and experience of life satisfaction among 330 Swiss eighth graders. A multivariate measure of career adaptability consisting of career choice readiness, planning, exploration, and confidence was applied. Based on Motivational Systems Theory four groups of predictors were assessed: positive emotional disposition, goal decidedness, capability beliefs and social context beliefs. Influence of gender, age, immigration background, parental educational level, and college-bound or vocational education plans were also assessed. Perceived social support and positive emotional disposition, non-immigration background, and continuing to vocational education were single significant predictors of more career adaptability development over the school year. Supporting the connection of career adaptability and positive youth development, increase in career adaptability over time predicted increase in sense of power and experience of life satisfaction.

Estimating Particle Shape and Orientation Using Volume Tensors

We develop statistical procedures for estimating shape and orientation of arbitrary three-dimensional particles. We focus on the case where particles cannot be observed directly, but only via sections. Volume tensors are used for describing particle shape and orientation, and we derive stereological estimators of the tensors. These estimators are combined to provide consistent estimators of the moments of the so-called particle cover density. The covariance structure associated with the particle cover density depends on the orientation and shape of the particles. For instance, if the distribution of the typical particle is invariant under rotations, then the covariance matrix is proportional to the identity matrix. We develop a non-parametric test for such isotropy. A flexible Lévy-based particle model is proposed, which may be analysed using a generalized method of moments in which the volume tensors enter. The developed methods are used to study the cell organization in the human brain cortex.

From doubled Chern–Simons–Maxwell lattice gauge theory to extensions of the toric code

We regularize compact and non-compact Abelian Chern–Simons–Maxwell theories on a spatial lattice using the Hamiltonian formulation. We consider a doubled theory with gauge fields living on a lattice and its dual lattice. The Hilbert space of the theory is a product of local Hilbert spaces, each associated with a link and the corresponding dual link. The two electric field operators associated with the link-pair do not commute. In the non-compact case with gauge group R, each local Hilbert space is analogous to the one of a charged “particle” moving in the link-pair group space R2 in a constant “magnetic” background field. In the compact case, the link-pair group space is a torus U(1)2 threaded by k units of quantized “magnetic” flux, with k being the level of the Chern–Simons theory. The holonomies of the torus U(1)2 give rise to two self-adjoint extension parameters, which form two non-dynamical background lattice gauge fields that explicitly break the manifest gauge symmetry from U(1) to Z(k). The local Hilbert space of a link-pair then decomposes into representations of a magnetic translation group. In the pure Chern–Simons limit of a large “photon” mass, this results in a Z(k)-symmetric variant of Kitaev’s toric code, self-adjointly extended by the two non-dynamical background lattice gauge fields. Electric charges on the original lattice and on the dual lattice obey mutually anyonic statistics with the statistics angle . Non-Abelian U(k) Berry gauge fields that arise from the self-adjoint extension parameters may be interesting in the context of quantum information processing.

HIV-1 Transmission During Recent Infection and During Treatment Interruptions as Major Drivers of New Infections in the Swiss HIV Cohort Study.

BACKGROUND  Reducing the fraction of transmissions during recent human immunodeficiency virus (HIV) infection is essential for the population-level success of "treatment as prevention". METHODS  A phylogenetic tree was constructed with 19 604 Swiss sequences and 90 994 non-Swiss background sequences. Swiss transmission pairs were identified using 104 combinations of genetic distance (1%-2.5%) and bootstrap (50%-100%) thresholds, to examine the effect of those criteria. Monophyletic pairs were classified as recent or chronic transmission based on the time interval between estimated seroconversion dates. Logistic regression with adjustment for clinical and demographic characteristics was used to identify risk factors associated with transmission during recent or chronic infection. FINDINGS  Seroconversion dates were estimated for 4079 patients on the phylogeny, and comprised between 71 (distance, 1%; bootstrap, 100%) to 378 transmission pairs (distance, 2.5%; bootstrap, 50%). We found that 43.7% (range, 41%-56%) of the transmissions occurred during the first year of infection. Stricter phylogenetic definition of transmission pairs was associated with higher recent-phase transmission fraction. Chronic-phase viral load area under the curve (adjusted odds ratio, 3; 95% confidence interval, 1.64-5.48) and time to antiretroviral therapy (ART) start (adjusted odds ratio 1.4/y; 1.11-1.77) were associated with chronic-phase transmission as opposed to recent transmission. Importantly, at least 14% of the chronic-phase transmission events occurred after the transmitter had interrupted ART. CONCLUSIONS  We demonstrate a high fraction of transmission during recent HIV infection but also chronic transmissions after interruption of ART in Switzerland. Both represent key issues for treatment as prevention and underline the importance of early diagnosis and of early and continuous treatment.

Biomarkers of pulmonary hypertension in patients with scleroderma: a case-control study.

INTRODUCTION Significant pulmonary vascular disease is a leading cause of death in patients with scleroderma, and early detection and early medical intervention are important, as they may delay disease progression and improve survival and quality of life. Although several biomarkers have been proposed, there remains a need to define a reliable biomarker of early pulmonary vascular disease and subsequent development of pulmonary hypertension (PH). The purpose of this study was to define potential biomarkers for clinically significant pulmonary vascular disease in patients with scleroderma. METHODS The circulating growth factors basic fibroblast growth factor, placental growth factor (PlGF), vascular endothelial growth factor (VEGF), hepatocyte growth factor, and soluble VEGF receptor 1 (sFlt-1), as well as cytokines (interleukin [IL]-1β IL-2, IL-4, IL-5, IL-8, IL-10, IL-12, IL-13, tumor necrosis factor-α, and interferon-γ), were quantified in patients with scleroderma with PH (n = 37) or without PH (n = 40). In non-parametric unadjusted analyses, we examined associations of growth factor and cytokine levels with PH. In a subset of each group, a second set of earlier samples, drawn 3.0±1.6 years earlier, were assessed to determine the changes over time. RESULTS sFlt-1 (p = 0.02) and PlGF (p = 0.02) were higher in the PH than in the non-PH group. sFlt-1 (ρ = 0.3245; p = 0.01) positively correlated with right ventricular systolic pressure. Both PlGF (p = 0.03) and sFlt-1 (p = 0.04) positively correlated with the ratio of forced vital capacity to diffusing capacity for carbon monoxide (DLCO), and both inversely correlated with DLCO (p = 0.01). Both PlGF and sFlt-1 levels were stable over time in the control population. CONCLUSIONS Our study demonstrated clear associations between regulators of angiogenesis (sFlt-1 and PlGF) and measures of PH in scleroderma and that these growth factors are potential biomarkers for PH in patients with scleroderma. Larger longitudinal studies are required for validation of our results.

Peri-implant soft tissue colour around titanium and zirconia abutments: a prospective randomized controlled clinical study

OBJECTIVES To objectively determine the difference in colour between the peri-implant soft tissue at titanium and zirconia abutments. MATERIALS AND METHODS Eleven patients, each with two contralaterally inserted osteointegrated dental implants, were included in this study. The implants were restored either with titanium abutments and porcelain-fused-to-metal crowns, or with zirconia abutments and ceramic crowns. Prior and after crown cementation, multi-spectral images of the peri-implant soft tissues and the gingiva of the neighbouring teeth were taken with a colorimeter. The colour parameters L*, a*, b*, c* and the colour differences ΔE were calculated. Descriptive statistics, including non-parametric tests and correlation coefficients, were used for statistical analyses of the data. RESULTS Compared to the gingiva of the neighbouring teeth, the peri-implant soft tissue around titanium and zirconia (test group), showed distinguishable ΔE both before and after crown cementation. Colour differences around titanium were statistically significant different (P = 0.01) only at 1 mm prior to crown cementation compared to zirconia. Compared to the gingiva of the neighbouring teeth, statistically significant (P < 0.01) differences were found for all colour parameter, either before or after crown cementation for both abutments; more significant differences were registered for titanium abutments. Tissue thickness correlated positively with c*-values for titanium at 1 mm and 2 mm from the gingival margin. CONCLUSIONS Within their limits, the present data indicate that: (i) The peri-implant soft tissue around titanium and zirconia showed colour differences when compared to the soft tissue around natural teeth, and (ii) the peri-implant soft tissue around zirconia demonstrated a better colour match to the soft tissue at natural teeth than titanium.

Evaluation of 3-dimensional superimposition techniques on various skeletal structures of the head using surface models.

OBJECTIVES To test the applicability, accuracy, precision, and reproducibility of various 3D superimposition techniques for radiographic data, transformed to triangulated surface data. METHODS Five superimposition techniques (3P: three-point registration; AC: anterior cranial base; AC + F: anterior cranial base + foramen magnum; BZ: both zygomatic arches; 1Z: one zygomatic arch) were tested using eight pairs of pre-existing CT data (pre- and post-treatment). These were obtained from non-growing orthodontic patients treated with rapid maxillary expansion. All datasets were superimposed by three operators independently, who repeated the whole procedure one month later. Accuracy was assessed by the distance (D) between superimposed datasets on three form-stable anatomical areas, located on the anterior cranial base and the foramen magnum. Precision and reproducibility were assessed using the distances between models at four specific landmarks. Non parametric multivariate models and Bland-Altman difference plots were used for analyses. RESULTS There was no difference among operators or between time points on the accuracy of each superimposition technique (p>0.05). The AC + F technique was the most accurate (D<0.17 mm), as expected, followed by AC and BZ superimpositions that presented similar level of accuracy (D<0.5 mm). 3P and 1Z were the least accurate superimpositions (0.790.05), the detected structural changes differed significantly between different techniques (p<0.05). Bland-Altman difference plots showed that BZ superimposition was comparable to AC, though it presented slightly higher random error. CONCLUSIONS Superimposition of 3D datasets using surface models created from voxel data can provide accurate, precise, and reproducible results, offering also high efficiency and increased post-processing capabilities. In the present study population, the BZ superimposition was comparable to AC, with the added advantage of being applicable to scans with a smaller field of view.