Predicting the Safety and Effectiveness of Inferior Vena Cava Filters (PRESERVE): Outcomes at 12 months.

OBJECTIVE: To determine the safety and effectiveness of vena cava filters (VCFs). METHODS: A total of 1429 participants (62.7 ± 14.7 years old; 762 [53.3% male]) consented to enroll in this prospective, nonrandomized study at 54 sites in the United States between October 10, 2015, and March 31, 2019. They were evaluated at baseline and at 3, 6, 12, 18, and 24 months following VCF implantation. Participants whose VCFs were removed were followed for 1 month after retrieval. Follow-up was performed at 3, 12, and 24 months. Predetermined composite primary safety (freedom from perioperative serious adverse events [AEs] and from clinically significant perforation, VCF embolization, caval thrombotic occlusion, and/or new deep vein thrombosis [DVT] within 12-months) and effectiveness (composite comprising procedural and technical success and freedom from new symptomatic pulmonary embolism [PE] confirmed by imaging at 12-months in situ or 1 month postretrieval) end points were assessed. RESULTS: VCFs were implanted in 1421 patients. Of these, 1019 (71.7%) had current DVT and/or PE. Anticoagulation therapy was contraindicated or had failed in 1159 (81.6%). One hundred twenty-six (8.9%) VCFs were prophylactic. Mean and median follow-up for the entire population and for those whose VCFs were not removed was 243.5 ± 243.3 days and 138 days and 332.6 ± 290 days and 235 days, respectively. VCFs were removed from 632 (44.5%) patients at a mean of 101.5 ± 72.2 days and median 86.3 days following implantation. The primary safety end point and primary effectiveness end point were both achieved. Procedural AEs were uncommon and usually minor, but one patient died during attempted VCF removal. Excluding strut perforation greater than 5 mm, which was demonstrated on 31 of 201 (15.4%) patients' computed tomography scans available to the core laboratory, and of which only 3 (0.2%) were deemed clinically significant by the site investigators, VCF-related AEs were rare (7 of 1421, 0.5%). Postfilter, venous thromboembolic events (none fatal) occurred in 93 patients (6.5%), including DVT (80 events in 74 patients [5.2%]), PE (23 events in 23 patients [1.6%]), and/or caval thrombotic occlusions (15 events in 15 patients [1.1%]). No PE occurred in patients following prophylactic placement. CONCLUSIONS: Implantation of VCFs in patients with venous thromboembolism was associated with few AEs and with a low incidence of clinically significant PEs.

Combined diffractive optical elements with adjustable optical properties controlled by a relative rotation: tutorial.

A pair of adjacent transmissive diffractive optical elements (DOEs) forms a combined DOE with tunable optical properties, as, for example, a diffractive lens with an adjustable focal length. The optical properties are controlled by a relative movement of the two DOEs, such as a translation or a rotation around the optical axis. Here we discuss various implementations of this principle, such as tunable diffractive lenses, axicons, vortex plates, and aberration correction devices. We discuss the limits of the tuning range and of diffraction efficiency. Furthermore, it is demonstrated how chromatic aberrations can be suppressed by using multi-order DOEs.

Demonstration of a multi-color diffractive lens with adjustable focal length.

A pair of combined diffractive optical elements (DOEs) realizes a so-called moiré lens, with an optical power which can be tuned by a mutual rotation of the two DOEs around their central optical axis. Earlier demonstrated moiré lenses still suffered from chromatic aberrations. Here we experimentally investigate a multi-color version of such a lens, realized by a pair of multi-order DOEs. These DOEs have a deeper surface structure which modulates the phase of the transmitted light wave by several multiples of 2π. The corresponding multi-order moiré lenses all have the same focal length at a fixed set of harmonic wavelengths within the white light spectrum. The experiments demonstrate that multi-order moiré lenses have significantly reduced chromatic aberrations. We investigate the performance of the lens for narrow band and white light imaging applications.

Airflow Obstruction and Use of Solid Fuels for Cooking or Heating: BOLD Results.

RATIONALE: Evidence supporting the association of COPD or airflow obstruction with use of solid fuels is conflicting and inconsistent. OBJECTIVE: To assess the association of airflow obstruction with self-reported use of solid fuels for cooking or heating. METHODS: We analysed 18,554 adults from the BOLD study, who had provided acceptable post-bronchodilator spirometry measurements and information on use of solid fuels. The association of airflow obstruction with use of solid fuels for cooking or heating was assessed by sex, within each site, using regression analysis. Estimates were stratified by national income and meta-analysed. We carried out similar analyses for spirometric restriction, chronic cough and chronic phlegm. MEASUREMENTS AND MAIN RESULTS: We found no association between airflow obstruction and use of solid fuels for cooking or heating (ORmen=1.20, 95%CI 0.94-1.53; ORwomen=0.88, 95%CI 0.67-1.15). This was true for low/middle and high income sites. Among never smokers there was also no evidence of an association of airflow obstruction with use of solid fuels (ORmen=1.00, 95%CI 0.57-1.76; ORwomen=1.00, 95%CI 0.76-1.32). Overall, we found no association of spirometric restriction, chronic cough or chronic phlegm with the use of solid fuels. However, we found that chronic phlegm was more likely to be reported among female never smokers and those who had been exposed for ≥20 years. CONCLUSION: Airflow obstruction assessed from post-bronchodilator spirometry was not associated with use of solid fuels for cooking or heating.

Remote focusing in confocal microscopy by means of a modified Alvarez lens.

Alvarez lenses are actuated lens-pairs which allow one to tune the optical power by mechanical displacement of subelements. Here, we show that a recently realized modified Alvarez lens design which does not require mechanical actuation can be integrated into a confocal microscope. Instead of mechanically moving them, the sublenses are imaged onto each other in a 4f-configuration, where the lateral image shift leading to a change in optical power is created by a galvo-mirror. The avoidance of mechanical lens shifts leads to a large speed gain for axial (and hence also 3D) image scans compared to classical Alvarez lenses. We demonstrate that the suggested operation principle is compatible with confocal microscopy. In order to optimize the system, we have drawn advantage of the flexibility a liquid-crystal spatial light modulator offers for the implementation. For given specifications, dedicated diffractive optical elements or freeform elements can be used in combination with resonant galvo-scanners or acousto-optic beam deflectors, to achieve even faster z-scans than reported here, reaching video rate.

A multi-modal stereo microscope based on a spatial light modulator.

Spatial Light Modulators (SLMs) can emulate the classic microscopy techniques, including differential interference (DIC) contrast and (spiral) phase contrast. Their programmability entails the benefit of flexibility or the option to multiplex images, for single-shot quantitative imaging or for simultaneous multi-plane imaging (depth-of-field multiplexing). We report the development of a microscope sharing many of the previously demonstrated capabilities, within a holographic implementation of a stereo microscope. Furthermore, we use the SLM to combine stereo microscopy with a refocusing filter and with a darkfield filter. The instrument is built around a custom inverted microscope and equipped with an SLM which gives various imaging modes laterally displaced on the same camera chip. In addition, there is a wide angle camera for visualisation of a larger region of the sample.

Predicting the Safety and Effectiveness of Inferior Vena Cava Filters (PRESERVE): Outcomes at 12 months.

OBJECTIVE: To determine the safety and effectiveness of vena cava filters (VCFs). METHODS: A total of 1429 participants (62.7 ± 14.7 years old; 762 [53.3% male]) consented to enroll in this prospective, nonrandomized study at 54 sites in the United States between October 10, 2015, and March 31, 2019. They were evaluated at baseline and at 3, 6, 12, 18, and 24 months following VCF implantation. Participants whose VCFs were removed were followed for 1 month after retrieval. Follow-up was performed at 3, 12, and 24 months. Predetermined composite primary safety (freedom from perioperative serious adverse events [AEs] and from clinically significant perforation, VCF embolization, caval thrombotic occlusion, and/or new deep vein thrombosis [DVT] within 12-months) and effectiveness (composite comprising procedural and technical success and freedom from new symptomatic pulmonary embolism [PE] confirmed by imaging at 12-months in situ or 1 month postretrieval) end points were assessed. RESULTS: VCFs were implanted in 1421 patients. Of these, 1019 (71.7%) had current DVT and/or PE. Anticoagulation therapy was contraindicated or had failed in 1159 (81.6%). One hundred twenty-six (8.9%) VCFs were prophylactic. Mean and median follow-up for the entire population and for those whose VCFs were not removed was 243.5 ± 243.3 days and 138 days and 332.6 ± 290 days and 235 days, respectively. VCFs were removed from 632 (44.5%) patients at a mean of 101.5 ± 72.2 days and median 86.3 days following implantation. The primary safety end point and primary effectiveness end point were both achieved. Procedural AEs were uncommon and usually minor, but one patient died during attempted VCF removal. Excluding strut perforation greater than 5 mm, which was demonstrated on 31 of 201 (15.4%) patients' computed tomography scans available to the core laboratory, and of which only 3 (0.2%) were deemed clinically significant by the site investigators, VCF-related AEs were rare (7 of 1421, 0.5%). Postfilter, venous thromboembolic events (none fatal) occurred in 93 patients (6.5%), including DVT (80 events in 74 patients [5.2%]), PE (23 events in 23 patients [1.6%]), and/or caval thrombotic occlusions (15 events in 15 patients [1.1%]). No PE occurred in patients following prophylactic placement. CONCLUSIONS: Implantation of VCFs in patients with venous thromboembolism was associated with few AEs and with a low incidence of clinically significant PEs.

Association between DHEAS and bone loss in postmenopausal women: a 15-year longitudinal population-based study.

Our aim was to examine the association between serum dehydroepiandrosterone sulfate (DHEAS) at baseline and BMD change at the femoral neck (FN) and lumbar spine (LS) in postmenopausal women during a 15-year follow-up. All participants were from the Chingford Study. BMD at the FN and LS were measured eight times during the 15-year follow-up by dual-energy X-ray absorptiometry. DHEAS at baseline was measured using radioimmunoassay. Data on height, weight, and hormone-replacement therapy (HRT) status were obtained at each visit. Multilevel linear regression modeling was used to examine the association between longitudinal BMD change at the FN and LS and DHEAS at baseline. Postmenopausal women (n = 1,003) aged 45-68 years (mean 54.7) at baseline were included in the study. After adjustment for baseline age, estradiol, HRT, and BMI, BMD at the FN decreased on average 0.49% (95% CI 0.31-0.71%) per year; and the decline was slowed down by 0.028% per squared year. Increase of DHEAS (each micromole per liter) was associated with 0.49% less bone loss at the FN (95% CI 0.21-0.71%, P = 0.001). However, this strong association became slightly weaker over time. Similar but weaker results were obtained for LS BMD. Our data suggest that high serum DHEAS at baseline is associated with less bone loss at both FN and LS and this association diminishes over time. The nature of the association is unclear, but such an association implies that, in managing BMD loss, women might benefit from maintaining a high level of DHEAS.

Variance decomposition of protein profiles from antibody arrays using a longitudinal twin model.

BACKGROUND: The advent of affinity-based proteomics technologies for global protein profiling provides the prospect of finding new molecular biomarkers for common, multifactorial disorders. The molecular phenotypes obtained from studies on such platforms are driven by multiple sources, including genetic, environmental, and experimental components. In characterizing the contribution of different sources of variation to the measured phenotypes, the aim is to facilitate the design and interpretation of future biomedical studies employing exploratory and multiplexed technologies. Thus, biometrical genetic modelling of twin or other family data can be used to decompose the variation underlying a phenotype into biological and experimental components. RESULTS: Using antibody suspension bead arrays and antibodies from the Human Protein Atlas, we study unfractionated serum from a longitudinal study on 154 twins. In this study, we provide a detailed description of how the variation in a molecular phenotype in terms of protein profile can be decomposed into familial i.e. genetic and common environmental; individual environmental, short-term biological and experimental components. The results show that across 69 antibodies analyzed in the study, the median proportion of the total variation explained by familial sources is 12% (IQR 1-22%), and the median proportion of the total variation attributable to experimental sources is 63% (IQR 53-72%). CONCLUSION: The variability analysis of antibody arrays highlights the importance to consider variability components and their relative contributions when designing and evaluating studies for biomarker discoveries with exploratory, high-throughput and multiplexed methods.

Offspring's leukocyte telomere length, paternal age, and telomere elongation in sperm.

Leukocyte telomere length (LTL) is a complex genetic trait. It shortens with age and is associated with a host of aging-related disorders. Recent studies have observed that offspring of older fathers have longer LTLs. We explored the relation between paternal age and offspring's LTLs in 4 different cohorts. Moreover, we examined the potential cause of the paternal age on offspring's LTL by delineating telomere parameters in sperm donors. We measured LTL by Southern blots in Caucasian men and women (n=3365), aged 18-94 years, from the Offspring of the Framingham Heart Study (Framingham Offspring), the NHLBI Family Heart Study (NHLBI-Heart), the Longitudinal Study of Aging Danish Twins (Danish Twins), and the UK Adult Twin Registry (UK Twins). Using Southern blots, Q-FISH, and flow-FISH, we also measured telomere parameters in sperm from 46 young (<30 years) and older (>50 years) donors. Paternal age had an independent effect, expressed by a longer LTL in males of the Framingham Offspring and Danish Twins, males and females of the NHLBI-Heart, and females of UK Twins. For every additional year of paternal age, LTL in offspring increased at a magnitude ranging from half to more than twice of the annual attrition in LTL with age. Moreover, sperm telomere length analyses were compatible with the emergence in older men of a subset of sperm with elongated telomeres. Paternal age exerts a considerable effect on the offspring's LTL, a phenomenon which might relate to telomere elongation in sperm from older men. The implications of this effect deserve detailed study.

Comparative protein profiling of serum and plasma using an antibody suspension bead array approach.

In the pursuit towards a systematic analysis of human diseases, array-based approaches within antibody proteomics offer high-throughput strategies to discover protein biomarkers in serum and plasma. To investigate the influence of sample preparation on such discovery attempts, we report on a systematic effort to compare serum and plasma protein profiles determined with an antibody suspension bead array. The intensity levels were used to define protein profiles and no significant differences between serum and plasma were observed for 79% of the 174 antibodies (targeting 156 proteins). By excluding 36 antibodies giving rise to differential intensity levels, cluster analysis revealed donor-specific rather than preparation-dependent grouping. With a cohort from a clinically relevant medical condition, the metabolic syndrome, the influence of the sample type on a multiplexed biomarker discovery approach was further investigated. Independent comparisons of protein profiles in serum and plasma revealed an antibody targeting ADAMTSL-4, a protein that would qualify to be studied further in association with the condition. In general, the preparation type had an impact on the results of the applied antibody suspension bead array, and while the technical variability was equal, plasma offered a greater biological variability and allowed to give rise to more discoveries than serum.

The association between physical activity in leisure time and leukocyte telomere length.

BACKGROUND: Physical inactivity is an important risk factor for many aging-related diseases. Leukocyte telomere dynamics (telomere length and age-dependent attrition rate) are ostensibly a biological indicator of human aging. We therefore tested the hypothesis that physical activity level in leisure time (over the past 12 months) is associated with leukocyte telomere length (LTL) in normal healthy volunteers. METHODS: We studied 2401 white twin volunteers, comprising 2152 women and 249 men, with questionnaires on physical activity level, smoking status, and socioeconomic status. Leukocyte telomere length was derived from the mean terminal restriction fragment length and adjusted for age and other potential confounders. RESULTS: Leukocyte telomere length was positively associated with increasing physical activity level in leisure time (P< .001); this association remained significant after adjustment for age, sex, body mass index, smoking, socioeconomic status, and physical activity at work. The LTLs of the most active subjects were 200 nucleotides longer than those of the least active subjects (7.1 and 6.9 kilobases, respectively; P= .006). This finding was confirmed in a small group of twin pairs discordant for physical activity level (on average, the LTL of more active twins was 88 nucleotides longer than that of less active twins; P= .03). CONCLUSIONS: A sedentary lifestyle (in addition to smoking, high body mass index, and low socioeconomic status) has an effect on LTL and may accelerate the aging process. This provides a powerful message that could be used by clinicians to promote the potentially antiaging effect of regular exercise.

Genetic loci linked to pituitary-thyroid axis set points: a genome-wide scan of a large twin cohort.

OBJECTIVE: Previous studies have shown that circulating concentrations of TSH, free T4, and free T3 are genetically regulated, but the genes responsible remain largely unknown. The aim of this study was to identify genetic loci associated with these parameters. DESIGN: We performed a multipoint, nonparametric genome-wide linkage scan of 613 female dizygotic twin pairs. All subjects were euthyroid (TSH 0.4-4.0 mU/liter) with negative thyroid peroxidase antibodies and no history of thyroid disease. The genome scan comprised 737 microsatellite markers supplemented with dinucleotide markers. Data were analyzed using residualized thyroid hormone data after adjustment for age, smoking, and body mass index. RESULTS: Multipoint linkage analysis gave linkage peaks for free T4 on chromosome 14q13 and 18q21 [logarithm of odds (LOD) 2.4-3.2]; TSH on chromosomes 2q36, 4q32, and 9q34 (LOD 2.1-3.2); and free T3 on chromosomes 7q36, 8q22, and 18q21 (LOD 2.0-2.3). CONCLUSIONS: This study has identified eight genomic locations with linkage of LOD of 2.0 or greater. These results should enable targeted positional candidate and positional cloning studies to advance our understanding of genetic control of the pituitary-thyroid axis.

Upgrading a microscope with a spiral phase plate.

We present the implementation of a spiral phase plate in a standard bright-field microscope to enhance the contrast of phase and amplitude samples. The method can be employed in all types of microscopy where standard phase contrast methods are applicable, for example, in bright-field transmission or reflection microscopy using an illumination source with partial spatial coherence. The spiral phase filter is placed into an accessible Fourier plane of the imaging path of the microscope. It is shown that this produces not only a strong contrast enhancement but in theory also improves the spatial resolution of the microscope for white light. A series of different set-ups for transmissive or reflective samples, including epi-illumination, are presented to demonstrate the practical range of applications of this contrasting method. A minute shift of the spiral phase plate out of the centre results in relief-like images that are similar to those obtained by differential interference contrast microscopy. A series of such relief-like images can be numerically processed to obtain quantitative phase and amplitude information of the sample.

Normal variations in personality are associated with coital orgasmic infrequency in heterosexual women: a population-based study.

INTRODUCTION: As many as 20-30% of women report an inability to orgasm during sexual intercourse. Some female sexual problems have been reported to cluster with psychological and social problems. Underlying personality type may play a role in the development or maintenance of such problems. AIM: The aim of this study was to investigate whether certain domains of personality are associated with female coital orgasmic infrequency. To our knowledge this is the first such study in a large unselected population. METHODS: A total of 2632 women (mean age 51) from the TwinsUK registry completed questionnaires relating to personality and sexual behavior. Personality domains were assessed using the validated Ten-Item Personality Index (TIPI). Coital orgasmic frequency was measured using a seven-point Likert scale. MAIN OUTCOME MEASURES: Using logistic regression, we investigated whether variations in five domains of personality are associated with female coital orgasmic infrequency. Discordant twin analysis was used to verify findings. RESULTS: Introversion (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.7-3.7), emotional instability (OR 2.0, 95% CI 1.3-3.1), and not being open to new experience (OR 2.4, 95% CI 1.6-3.6) were significantly associated with orgasmic infrequency, whereas indices of agreeableness and conscientiousness were not significantly associated with orgasm frequency. CONCLUSION: Specific personality subtypes appear to be significant risk factors for orgasmic infrequency. Consideration of these behavioral risk factors may need to be incorporated into research into female orgasmic disorder, and possible approaches to its treatment.

Linkage of genes to total lean body mass in normal women.

BACKGROUND: Total lean body mass (LEAN-tot) is one of the three major components of body weight. Its deterioration is a risk factor for frailty. Despite this, there are few studies examining the contribution of genetic factors. OBJECTIVE: Our objective was to examine the contribution of genetic factors for LEAN-tot variation, including a genome-wide search for the genes. RESEARCH METHODS: Dual-energy x-ray absorptiometry measurements of LEAN-tot were obtained from each of the 3180 United Kingdom females (509 monozygotic and 1081 dizygotic twin pairs). Contribution of genetic factors was assessed using variance component analysis. A genome-wide linkage analysis was performed on the dizygotic twins using a modified version of the Haseman-Elston method. RESULTS: Age, body height, total fat, and bone mass were correlated with LEAN-tot, and commonly explained 52% of the LEAN-tot variation. The crude heritability estimate was 74.0 +/- 4.0%, after adjustment for the aforementioned factors; 65.2 +/- 4.6% was attributable to independent genetic effects. Significant (P < 0.001) genetic correlations were found between LEAN-tot and bone mass, and LEAN-tot and total fat. Adjusted only for age, LEAN-tot showed no significant linkage. After adjustment for all covariates, significant linkage (LOD = 4.49 and 3.62) was observed at chromosome 12q24.3 and 14q22.3, respectively. Additional peaks of interest were on 7p15.3-15.1 (LOD = 2.86) and 8p22 (LOD = 2.83). CONCLUSIONS: LEAN-tot measured by dual-energy x-ray absorptiometry is highly heritable, independent of other body measures. This first genomic search for genes associated with the lean component of body mass suggests significant linkage to quantitative trait loci on chromosomes 12 and 14.

Nevus size and number are associated with telomere length and represent potential markers of a decreased senescence in vivo.

Nevus counts represent one of the strongest risk factors for melanoma. They appear in childhood and adolescence and involute from middle age onwards. Recent evidence has shown that nevus cells undergo oncogene-induced senescence involving the p16/retinoblastoma pathway. However, telomere length also influences senescence in proliferative somatic cells and varies between individuals. This study explores whether telomere length measured in white cells is associated with nevus count and size in 1,897 Caucasian women ages 18 to 79 years. Total body nevus counts were positively correlated with white cell telomere length (mean, 7.09 kbp; range, 5.09-9.37) after adjustment for age (P = 0.0001). Age-adjusted telomere length was also associated with nevus count for nevi above 5 mm in diameter (P = 0.04). Subjects in the top category for nevus count had an average age-adjusted telomere length 150 bp longer than those in the lowest category. The positive correlation between white cell telomere length and nevi number and size may reflect an increased replicative potential (reduced senescence) in individuals with longer telomeres, which may not be melanocyte specific. Understanding mechanisms influencing the induction and involution of nevi will not only help in understanding the pathophysiology of melanoma but should also shed light on the complex relationship between aging and cancer.

Lack of association between leukocyte telomere length and genetic variants in two ageing-related candidate genes.

BACKGROUND: Leukocyte telomere length, a putative marker of ageing, is a highly variable and heritable complex trait. In order to determine the possible underlying genetic variants for leukocyte telomere length variation, we conducted an association study of leukocyte telomere length and two candidate genes for ageing-related traits, TGFB1 and KLOTHO, in a female Caucasian dizygotic twin population. METHODS AND MATERIALS: Terminal restriction fragment (TRF) length, an index of telomere length, was measured using Southern Blotting. Six and four single nucleotide polymorphisms (SNP) were genotyped in TGFB1 and KLOTHO gene, respectively, and tested for association. When there is strong LD between SNPs (r(2) > 0.5), haplotypic association was investigated using haplotype trend regression approach. RESULTS: All SNPs were in Hardy-Weinberg equilibrium (p > 0.05). No significant association was detected for individual SNPs (p > 0.101), or two-locus haplotypes (p = 0.7497) with TRF variation. CONCLUSION: We failed to find any significant association between leukocyte telomere length and 10 SNPs in two ageing-related candidate genes, TGFB1 and KLOTHO. This result suggests that while we could not exclude minor effects, none of 10 SNPs in these two candidate genes showed significant association with the variation of leukocyte telomere length in our cohort. But as it is unclear whether telomere length dynamics is the cause or the effect of the ageing process, it is still possible the genes are associated with ageing via alternate mechanisms.

Wavefront correction of spatial light modulators using an optical vortex image.

We present a fast and flexible non-interferometric method for the correction of small surface deviations on spatial light modulators, based on the Gerchberg-Saxton algorithm. The surface distortion information is extracted from the shape of a single optical vortex, which is created by the light modulator. The method can be implemented in optical tweezers systems for an optimization of trapping fields, or in an imaging system for an optimization of the point-spread-function of the entire image path.

Heritability of the second to fourth digit ratio (2d:4d): A twin study.

The second to fourth finger length ratio (2d:4d) has been the subject of much recent work and is thought to be related to diverse gender and hormone-related traits including sports ability, disease susceptibility, attractiveness and sexuality. It is established in utero and remains constant in adulthood. Familial clustering has been thought to contribute to the development of 2d:4d from early studies but no twin studies exploring heritability have been reported to date. In this study, a sample of 456 female twin pairs (148 monozygotic [MZ], 308 dizygotic [DZ]) aged 18 to 79 years was used to estimate the heritability of 2d:4d for the right and left hands. Finger lengths were derived from hand x-rays. Variance components analysis was used to estimate and contrast genetic and environmental effects on this phenotype. The mean 2d:4d was 0.92 (SD = 0.001) for both hands. The MZ intraclass correlation was higher than in DZ (.66 vs. .35 for right 2d:4d, and .71 vs. .37 for left 2d:4d). The best fit model included additive polygenic and unique environmental effects ('AE' model), with no significant common environmental effects detected. Heritability was estimated to be approximately 66% for 2d:4d (95% confidence interval 0.5-0.78). These results suggest a substantial genetic contribution to the determination of this hormonally related skeletal ratio in women, which could be more influential than the effects of common prenatal environmental factors. However the current study design does not preclude the possibility of confounding between heritability estimates and unobserved prenatal effects.