Implicit gender bias in the diagnosis and treatment of type 2 diabetes: A randomized online study.

AIMS: Implicit gender biases (IGBs) are unconscious evaluations about a person based on gender. IGBs of healthcare providers may affect medical decision making. This study investigated whether IGBs and genders of patients and general practitioners (GPs) influence diagnostics and treatment decisions in the context of diabetes type 2. METHODS: Ninety-nine GPs participated in this randomized online study. Implicit Associations Tasks were used to measure two IGBs, related to lifestyle (women have a healthier lifestyle than men) and communication (men are less communicative than women). Clinical decisions regarding type 2 diabetes were measured with vignettes that included a fictional male or female patient case. RESULTS: Female GPs exhibited a significant lifestyle IGB (p < 0.001). GPs of both genders exhibited a significant communication IGB (p < 0.001). Several associations between IGBs and clinical decisions were found. The gender of the vignette character affected several outcomes, for example GPs were less certain in the diabetes diagnosis when the character was a woman (p < 0.001). CONCLUSION: We demonstrated that GPs have IGBs and these biases as well as patient's gender affect decisions of GP's when they are solving a diabetes vignette case. Future research is needed to understand the most important consequences of IGBs in the context of type 2 diabetes.

Human Echolocators Have Better Localization Off Axis.

Here, we report novel empirical results from a psychophysical experiment in which we tested the echolocation abilities of nine blind adult human experts in click-based echolocation. We found that they had better acuity in localizing a target and used lower intensity emissions (i.e., mouth clicks) when a target was placed 45° off to the side compared with when it was placed at 0° (straight ahead). We provide a possible explanation of the behavioral result in terms of binaural-intensity signals, which appear to change more rapidly around 45°. The finding that echolocators have better echo-localization off axis is surprising, because for human source localization (i.e., regular spatial hearing), it is well known that performance is best when targets are straight ahead (0°) and decreases as targets move farther to the side. This may suggest that human echolocation and source hearing rely on different acoustic cues and that human spatial hearing has more facets than previously thought.

A spatial and temporal characterisation of single proton acoustic waves in proton beam cancer therapy.

An in vivo range verification technology for proton beam cancer therapy, preferably in real-time and with submillimeter resolution, is desired to reduce the present uncertainty in dose localization. Acoustical imaging technologies exploiting possible local interactions between protons and microbubbles or nanodroplets might be an interesting option. Unfortunately, a theoretical model capable of characterising the acoustical field generated by an individual proton on nanometer and micrometer scales is still missing. In this work, such a model is presented. The proton acoustic field is generated by the adiabatic expansion of a region that is locally heated by a passing proton. To model the proton heat deposition, secondary electron production due to protons has been quantified using a semi-empirical model based on Rutherford's scattering theory, which reproduces experimentally obtained electronic stopping power values for protons in water within 10% over the full energy range. The electrons transfer energy into heat via electron-phonon coupling to atoms along the proton track. The resulting temperature increase is calculated using an inelastic thermal spike model. Heat deposition can be regarded as instantaneous, thus, stress confinement is ensured and acoustical initial conditions are set. The resulting thermoacoustic field in the nanometer and micrometer range from the single proton track is computed by solving the thermoacoustic wave equation using k-space Green's functions, yielding the characteristic amplitudes and frequencies present in the acoustic signal generated by a single proton in an aqueous medium. Wavefield expansion and asymptotic approximations are used to extend the spatial and temporal ranges of the proton acoustic field.

Tapering of the interventricular septum can affect ultrasound shear wave elastography: An in vitro and in silico study.

Shear wave elastography (SWE) has the potential to determine cardiac tissue stiffness from non-invasive shear wave speed measurements, important, e.g., for predicting heart failure. Previous studies showed that waves traveling in the interventricular septum (IVS) may display Lamb-like dispersive behaviour, introducing a thickness-frequency dependency in the wave speed. However, the IVS tapers across its length, which complicates wave speed estimation by introducing an additional variable to account for. The goal of this work is to assess the impact of tapering thickness on SWE. The investigation is performed by combining in vitro experiments with acoustic radiation force (ARF) and 2D finite element simulations, to isolate the effect of the tapering curve on ARF-induced and natural waves in the heart. The experiments show a 11% deceleration during propagation from the thick to the thin end of an IVS-mimicking tapered phantom plate. The numerical analysis shows that neglecting the thickness variation in the wavenumber-frequency domain can introduce errors of more than 30% in the estimation of the shear modulus, and that the exact tapering curve, rather than the overall thickness reduction, determines the dispersive behaviour of the wave. These results suggest that septal geometry should be accounted for when deriving cardiac stiffness with SWE.

Fundamental modeling of wave propagation in temporally relaxing media with applications to cardiac shear wave elastography.

Shear wave elastography (SWE) might allow non-invasive assessment of cardiac stiffness by relating shear wave propagation speed to material properties. However, after aortic valve closure, when natural shear waves occur in the septal wall, the stiffness of the muscle decreases significantly, and the effects of such temporal variation of medium properties on shear wave propagation have not been investigated yet. The goal of this work is to fundamentally investigate these effects. To this aim, qualitative results were first obtained experimentally using a mechanical setup, and were then combined with quantitative results from finite difference simulations. The results show that the amplitude and period of the waves increase during propagation, proportional to the relaxation of the medium, and that reflected waves can originate from the temporal stiffness variation. These general results, applied to literature data on cardiac stiffness throughout the heart cycle, predict as a major effect a period increase of 20% in waves propagating during a healthy diastolic phase, whereas only a 10% increase would result from the impaired relaxation of an infarcted heart. Therefore, cardiac relaxation can affect the propagation of waves used for SWE measurements and might even provide direct information on the correct relaxation of a heart.

Functional analysis of two haplotypes of the human endothelial protein C receptor gene.

OBJECTIVE: To confirm the effect of the endothelial protein receptor gene (PROCR) haplotypes H1 and H3 on venous thromboembolism (VTE), to study their effect on endothelial protein C receptor (EPCR) expression in human umbilical vein endothelial cells, and to investigate the functionality of H1 tagging single-nucleotide polymorphisms in an in vitro model. APPROACH AND RESULTS: Protein C (PC), activated PC, and soluble EPCR (sEPCR) levels were measured in 702 patients with VTE and 518 healthy individuals. All subjects were genotyped for PROCR H1 and H3. Human umbilical vein endothelial cells isolated from 111 umbilical cords were used to study the relation between PROCR haplotypes, PROCR mRNA, cellular distribution of EPCR, and rate of PC activation. Finally, the functionality of the intragenic PROCR H1 single-nucleotide polymorphisms was analyzed using a luciferase-based method. We confirmed that individuals carrying H1 have reduced VTE risk, increased plasma activated PC levels, and reduced plasma sEPCR levels and that individuals with the H3H3 genotype have an increased VTE risk and increased plasma sEPCR levels. In cultured human umbilical vein endothelial cells, H1 is associated with increased membrane-bound EPCR, increased rate of PC activation, and reduced sEPCR in conditioned medium, but does not significantly influence PROCR mRNA levels. In contrast, H3 is associated with reduced membrane-bound EPCR and increased sEPCR in human umbilical vein endothelial cell-conditioned medium, higher levels of a truncated mRNA isoform, and a lower rate of PC activation. Finally, we identified the g.2132T>C single-nucleotide polymorphism in intron 1 as an intragenic H1-specific functional single-nucleotide polymorphism. CONCLUSIONS: These results support a protective role of PROCR H1 against VTE and an increased risk of VTE associated with the H3 haplotype.

The introduction of a data-driven population health management approach in the Netherlands since 2019: The Extramural LUMC Academic Network data infrastructure.

Improving population health and reducing inequalities through better integrated health and social care services is high up on the agenda of policymakers internationally. In recent years, regional cross-domain partnerships have emerged in several countries, which aim to achieve better population health, quality of care and a reduction in the per capita costs. These cross-domain partnerships aim to have a strong data foundation and are committed to continuous learning in which data plays an essential role. This paper describes our approach towards the development of the regional integrative population-based data infrastructure Extramural LUMC (Leiden University Medical Center) Academic Network (ELAN), in which we linked routinely collected medical, social and public health data at the patient level from the greater The Hague and Leiden area. Furthermore, we discuss the methodological issues of routine care data and the lessons learned about privacy, legislation and reciprocities. The initiative presented in this paper is relevant for international researchers and policy-makers because a unique data infrastructure has been set up that contains data across different domains, providing insights into societal issues and scientific questions that are important for data driven population health management approaches.

The impact of the covid-19 pandemic on diabetes care: the perspective of healthcare providers across Europe.

AIMS: Covid-19 caused changes on the delivery of diabetes care. This study aimed to explore perceptions of healthcare providers across Europe concerning 1) the impact of covid-19 on delivery of diabetes care; 2) impact of changes in diabetes care on experienced workload; 3) experiences with video consultation in diabetes care. METHODS: Cross-sectional survey among healthcare providers in the Netherlands, United Kingdom, Turkey, Ukraine and Sweden, with a focus on primary care. RESULTS: The survey was completed by 180 healthcare providers. During the COVID-19 pandemic 57.1% of respondents provided less diabetes care and 72.8% observed a negative impact on people with diabetes. More than half of respondents (61.9%) expressed worries to some extent about getting overloaded by work. Although the vast majority considered their work meaningful (85.6%). Almost half of healthcare providers (49.4%) thought that after the pandemic video-consultation could be blended with face-to-face contact. CONCLUSIONS: Less diabetes care was delivered and a negative impact on people with diabetes was observed by healthcare providers. Despite healthcare providers' feeling overloaded, mental wellbeing seemed unaffected. Video consultations were seen as having potential. Given the remaining covid-19 risks and from the interest of proactive management of people with diabetes, these findings urge for further exploration of incorporating video consultation in diabetes care.

Episialin (MUC1) overexpression inhibits integrin-mediated cell adhesion to extracellular matrix components.

Episialin (MUC1) is a transmembrane molecule with a large mucin-like extracellular domain protruding high above the cell surface. The molecule is located at the apical side of most glandular epithelial cells, whereas in carcinoma cells it is often present at the entire surface and it is frequently expressed in abnormally large quantities. We have previously shown that overexpression of episialin reduces cell-cell interactions. Here we show that the integrin-mediated adhesion to extracellular matrix of transfectants of a melanoma cell line (A375), a transformed epithelial cell line (MDCK-ras-e) and a human breast epithelial cell line (HBL-100) is reduced by high levels of episialin. This reduction can be reversed by inducing high avidity of the beta 1 integrins by mAb TS2/16 (at least for beta 1-mediated adhesion). The adhesion can also be restored by redistribution of episialin on the cell surface by monoclonal antibodies into patches or caps. Similarly, capping of episialin on ZR-75-1 breast carcinoma cells, growing in suspension, caused adherence and spreading of these cells. We propose that there is a delicate balance between adhesion and anti-adhesion forces in episialin expressing cells, which can be shifted towards adhesion by strengthening the integrin-mediated adhesion, or towards anti-adhesion by increasing the level of expression of episialin.

Tolerance of combined submergence and salinity in the halophytic stem-succulent Tecticornia pergranulata.

BACKGROUND AND AIMS: Habitats occupied by many halophytes are not only saline, but are also prone to flooding. Few studies have evaluated submergence tolerance in halophytes. METHODS: Responses to submergence, at a range of salinity levels, were studied for the halophytic stem-succulent Tecticornia pergranulata subsp. pergranulata (syn. Halosarcia pergranulata subsp. pergranulata). Growth and total sugars in succulent stems were assessed as a function of time after submergence. Underwater net photosynthesis, dark respiration, total sugars, glycinebetaine, Na(+), Cl(-) and K(+), in succulent stems, were assessed in a NaCl dose-response experiment. KEY RESULTS: Submerged plants ceased to grow, and tissue sugars declined. Photosynthesis by succulent stems was reduced markedly when underwater, as compared with in air. Capacity for underwater net photosynthesis (P(N)) was not affected by 10-400 mM NaCl, but it was reduced by 30 % at 800 mM. Dark respiration, underwater, increased in succulent stems at 200-800 mM NaCl, as compared with those at 10 mM NaCl. On an ethanol-insoluble dry mass basis, K(+) concentration in succulent stems of submerged plants was equal to that in drained controls, across all NaCl treatments. Na(+) and Cl(-) concentrations, however, were elevated in stems of submerged plants, but so was glycinebetaine. Submerged stems increased in succulence, so solutes would have been 'diluted' on a tissue-water basis. CONCLUSIONS: Tecticornia pergranulata tolerates complete submergence, even in waters of high salinity. A 'quiescence response', i.e. no shoot growth, would conserve carbohydrates, but tissue sugars still declined with time. A low K(+) : Na(+) ratio, typical for tissues of succulent halophytes, was tolerated even during prolonged submergence, as evidenced by maintenance of underwater P(N) at up to 400 mM NaCl. Underwater P(N) provides O(2) and sugars, and thus should enhance survival of submerged plants.

Cell membrane-associated mucins and their adhesion-modulating property.

A class of highly sialylated glycoproteins with very large mucin-like domains that protrude high above the plasma membrane have been shown to strongly reduce cellular adhesion. In normal epithelial cells, where the expression is restricted to the luminal side of the cell, these molecules may prevent inadvertent closing of the lumen as a result of weak, non-specific protein-protein interactions between opposite luminal membranes. In malignant tumors cellular polarization is often lost, which can lead to the entire cell surface being covered by these molecules. The resulting strongly reduced adhesion and immune recognition properties may play an important role during invasion and metastasis.

Human Click-Based Echolocation of Distance: Superfine Acuity and Dynamic Clicking Behaviour.

Some people who are blind have trained themselves in echolocation using mouth clicks. Here, we provide the first report of psychophysical and clicking data during echolocation of distance from a group of 8 blind people with experience in mouth click-based echolocation (daily use for > 3 years). We found that experienced echolocators can detect changes in distance of 3 cm at a reference distance of 50 cm, and a change of 7 cm at a reference distance of 150 cm, regardless of object size (i.e. 28.5 cm vs. 80 cm diameter disk). Participants made mouth clicks that were more intense and they made more clicks for weaker reflectors (i.e. same object at farther distance, or smaller object at same distance), but number and intensity of clicks were adjusted independently from one another. The acuity we found is better than previous estimates based on samples of sighted participants without experience in echolocation or individual experienced participants (i.e. single blind echolocators tested) and highlights adaptation of the perceptual system in blind human echolocators. Further, the dynamic adaptive clicking behaviour we observed suggests that number and intensity of emissions serve separate functions to increase SNR. The data may serve as an inspiration for low-cost (i.e. non-array based) artificial 'cognitive' sonar and radar systems, i.e. signal design, adaptive pulse repetition rate and intensity. It will also be useful for instruction and guidance for new users of echolocation.

[A young man with a painful scrotum]. / Een jongeman met een pijnlijk scrotum.

A 16-year-old male patient with no known medical history presented at the Emergency Department (ED) with a 2-day history of pain and swelling in his right hemiscrotum. He was diagnosed with non-bacterial epididymitis and discharged home with medical advice. Six days after being diagnosed, the pain and swelling worsened and he was seen by a general practitioner who concluded that the symptoms were attributable to the previously diagnosed epididymitis. No further investigations were performed. Two days later he again presented at the ED, at which time colour Doppler echography revealed a testicular torsion of probably two days old. As after operative detorsion the testis was found to be non-vital, an orchidectomy was performed. This case illustrates that the diagnosis of epididymitis should always be reviewed in patients in whom the scrotum once again becomes painful. Early recognition and treatment of torsio testis gives a better chance of keeping the testis and therefore fertility.

Nonspherical vibrations of microbubbles in contact with a wall: a pilot study at low mechanical index.

Radially oscillating microbubbles can deform when in contact with a wall. These nonspherical shapes have a preferential orientation perpendicular to the wall. Conventional microscope setups for microbubble studies have their optical axis perpendicular to the wall (top view); consequently they have a limited view of the deformation of the bubble. We developed a method to image the bubble in a side view by integrating a mirror in the microscope setup. The image was recorded at 14.5 million frames per second by a high-speed camera. When insonified by a 1-MHz, 140-kPa ultrasound pulse, a 9-microm diameter coated bubble appeared spherical in the top view, but strongly nonspherical in the side view. Its shape was alternatively oblate and prolate, with maximum second order spherical harmonic amplitude equal to the radius.

Multiline 3D beamforming using micro-beamformed datasets for pediatric transesophageal echocardiography.

Until now, no matrix transducer has been realized for 3D transesophageal echocardiography (TEE) in pediatric patients. In 3D TEE with a matrix transducer, the biggest challenges are to connect a large number of elements to a standard ultrasound system, and to achieve a high volume rate (>200 Hz). To address these issues, we have recently developed a prototype miniaturized matrix transducer for pediatric patients with micro-beamforming and a small central transmitter. In this paper we propose two multiline parallel 3D beamforming techniques (µBF25 and µBF169) using the micro-beamformed datasets from 25 and 169 transmit events to achieve volume rates of 300 Hz and 44 Hz, respectively. Both the realizations use angle-weighted combination of the neighboring overlapping sub-volumes to avoid artifacts due to sharp intensity changes introduced by parallel beamforming. In simulation, the image quality in terms of the width of the point spread function (PSF), lateral shift invariance and mean clutter level for volumes produced by µBF25 and µBF169 are similar to the idealized beamforming using a conventional single-line acquisition with a fully-sampled matrix transducer (FS4k, 4225 transmit events). For completeness, we also investigated a 9 transmit-scheme (3 × 3) that allows even higher frame rates but found worse B-mode image quality with our probe. The simulations were experimentally verified by acquiring the µBF datasets from the prototype using a Verasonics V1 research ultrasound system. For both µBF169 and µBF25, the experimental PSFs were similar to the simulated PSFs, but in the experimental PSFs, the clutter level was ~10 dB higher. Results indicate that the proposed multiline 3D beamforming techniques with the prototype matrix transducer are promising candidates for real-time pediatric 3D TEE.

Polymorphism 10034C>T is located in a region regulating polyadenylation of FGG transcripts and influences the fibrinogen gamma'/gammaA mRNA ratio.

BACKGROUND: Fibrinogen gamma haplotype 2 (FGG-H2) is associated with reduced fibrinogen gamma' levels and fibrinogen gamma'/total fibrinogen ratios and with an increased deep-venous thrombosis (DVT) risk. Two FGG-H2 tagging single nucleotide polymorphisms (SNPs), 9615C>T and 10034C>T, are located in the region of alternative FGG pre-mRNA processing. 10034C>T is located in a GT-rich downstream sequence element (DSE) that comprises a putative cleavage stimulation factor (CstF) binding site. OBJECTIVES: To investigate the functionality of SNPs 9615C>T and 10034C>T, and the importance of the DSE containing 10034C>T. METHODS: Different minigene constructs containing FGG exon 9, intron 9, exon 10 and the 3' region were transiently transfected into HepG2 cells and quantitative real-time polymerase chain reaction was used to measure relative polyadenylation (pA) signal usage (pA1/pA2 ratio). RESULTS: Compared with the reference construct CC (9615C-10034C; FGG-H1; pA1/pA2 ratio set at 100%), the pA1/pA2 ratio of construct TT (9615T-10034T; FGG-H2) was 1.4-fold decreased (71.5%, P = 0.015). The pA1/pA2 ratio of construct CT (9615C-10034T) was almost 1.2-fold decreased (85.3%, P = 0.001), whereas the pA1/pA2 ratio of construct TC (9615T-10034C) did not differ significantly from the reference construct (101.6%, P = 0.890). Functionality of the putative CstF binding site was confirmed using constructs in which this site was deleted or its sequence altered by point mutations. CONCLUSIONS: SNP 10034C>T is located in a GT-rich DSE involved in regulating the usage of the pA2 signal of FGG, which may represent a CstF binding site. We propose that the 10034C>T change is the functional variation in FGG-H2 that is responsible for the reduction in the fibrinogen gamma'/total fibrinogen ratio and the increased DVT risk.

[Social issues in the doctor's clinic]. / De maatschappij in de spreekkamer.

Doctors are confronted with issues that arise in society. These social issues can affect patients' health. Solving these problems requires more than just prescribing a pill, as illustrated by the cases of three patients. The first patient is a 42-year-old male with cardiac symptoms, chronic lower back pain and an excessive use of tranquillizers. The welfare worker intervened and his demand for health care and use of tranquillizers diminished. The second patient is a 53-year-old female with symptoms of chronic back pain, migraine and depression. A labour dispute concerning her health eventually led to a referral to a project named 'social hospital', but actual assistance never took place due to the patient's alleged lack of time to participate. The third case concerns an 86-year-old female with postherpetic neuralgia who also suffered from loneliness. The patient's named welfare worker tried to get in touch with her, but the patient kept her at a distance. These three cases illustrate that it is very important to get to know the social network in a community in order to refer patients with social issues to the right person or place. Furthermore, prevention and early intervention strategies should be applied where possible. Doctors and local governments must act together in order to succeed in solving patient ill health as a result of social issues.

Synergistic functions of E2F7 and E2F8 are critical to suppress stress-induced skin cancer.

E2F transcription factors are important regulators of the cell cycle, and unrestrained activation of E2F-dependent transcription is considered to be an important driver of tumor formation and progression. Although highly expressed in normal skin and skin cancer, the role of the atypical E2Fs, E2F7 and E2F8, in keratinocyte homeostasis, regeneration and tumorigenesis is unknown. Surprisingly, keratinocyte-specific deletion of E2F7 and E2F8 in mice did not interfere with skin development and wound healing. However, the rate for successful isolation and establishment of E2f7/8-deficient primary keratinocyte cultures was much higher than for wild-type keratinocytes. Moreover, E2f7/8-deficient primary keratinocytes proliferate more efficiently under stress conditions, such as low/high confluence or DNA damage. Application of in vivo stress using the DMBA/TPA skin carcinogenesis protocol revealed that combined inactivation of E2f7/8 enhanced tumorigenesis and accelerated malignant progression. Loss of atypical E2Fs resulted in increased expression of E2F target genes, including E2f1. Additional loss of E2f1 did not rescue, but worsened skin tumorigenesis. We show that loss of E2F7/8 triggers apoptosis via induction of E2F1 in response to stress, indicating that the tumor-promoting effect of E2F7/8 inactivation can be partially compensated via E2F1-dependent apoptosis. Importantly, E2F7/8 repressed a large set of E2F target genes that are highly expressed in human patients with skin cancer. Together, our studies demonstrate that atypical E2Fs act as tumor suppressors, most likely via transcriptional repression of cell cycle genes in response to stress.

Inherited defects of coagulation Factor V: the thrombotic side.

DNA variations in the Factor V gene have played a major role in thrombosis research ever since the discovery of Factor V Leiden. Here, all relatively common DNA variations in the coding regions of the Factor V gene are discussed. Many of them have been associated with venous thrombosis or related diseases. However, most variations have been studied separately, without taking the presence of other variations in the same gene into account. This means that their association with disease should be interpreted with caution, as it may reflect linkage with another variation. An approach in which a haplotype-based analysis of the Factor V gene is combined with in vitro assays of recombinant proteins is advocated. Finally, a possible reason for the relatively polymorphic nature of the Factor V protein is discussed.

The association of prothrombin A19911G polymorphism with plasma prothrombin activity and venous thrombosis: results of the MEGA study, a large population-based case-control study.

BACKGROUND: Prothrombin (FII) G20210A mutation and elevated plasma prothrombin activity are known risk factors for venous thrombosis. The risk of venous thrombosis among 19911G carriers of the prothrombin A19911G polymorphism has not been extensively investigated. OBJECTIVES AND METHODS: We assessed prothrombin activity, FIIG20210A, and FIIA19911G polymorphisms in a large population-based case-control study, the Multiple Environmental and Genetic Assessment (MEGA) study of risk factors for venous thrombosis. Four thousand three hundred and sixty-five consecutive patients with a first episode of deep vein thrombosis of the leg or pulmonary embolism were included. The control group (n = 4779) consisted of partners of patients or persons gathered using a random-digit dialing method. We studied the effect of FIIA19911G polymorphism on prothrombin activity and thrombosis risk, also in combination with factor V Leiden. RESULTS: Among FII20210-GG control subjects, FII19911-GG carriers had 7.1% [95% confidence interval (CI): 5.7-8.5] higher mean prothrombin activity than FII19911-AA carriers and the risk for GG carriers was 1.43-fold increased compared to AA carriers [odds ratio (OR) 1.43; 95% CI: 1.27-1.61]. Among FII20210-GA control carriers, the mean prothrombin activity in both FII19911-AA and -AG carriers was nearly equivalent [131.7% and 133.4%; mean difference (95% CI) = 1.7% (-7.2-10.7)]. Because of genetic linkage, FII19911-GG carriers were very rare on a FII20210-GA background, as only one FII20210A carrier had FII19911-GG. In FII20210-GA carriers, the OR increased from 3.05 (95% CI: 2.17-4.27) in subjects with FII19911-AA to 3.33 (2.28-4.85) in subjects with FII19911-AG, compared to those with FII20210-GG and FII19911-AA. CONCLUSIONS: The FIIA19911G polymorphism is associated with mildly elevated prothrombin activity and is a risk factor for venous thrombosis.