Objective To assess the risk of venous thromboembolism from use of combined oral contraceptives according to progestogen type and oestrogen dose.Design National historical registry based cohort study. Setting Four registries in Denmark.Participants Non-pregnant Danish women aged 15-49 with no history of thrombotic disease and followed from January 2001 to December 2009. Main outcome measures Relative and absolute risks of first time venous thromboembolism.Results Within 8 010 290 women years of observation, 4307 first ever venous thromboembolic events were recorded and 4246 included, among which 2847 (67%) events were confirmed as certain. Compared with non-users of hormonal contraception, the relative risk of confirmed venous thromboembolism in users of oral contraceptives containing 30-40 µg ethinylestradiol with levonorgestrel was 2.9 (95% confidence interval 2.2 to 3.8), with desogestrel was 6.6 (5.6 to 7.8), with gestodene was 6.2 (5.6 to 7.0), and with drospirenone was 6.4 (5.4 to 7.5). With users of oral contraceptives with levonorgestrel as reference and after adjusting for length of use, the rate ratio of confirmed venous thromboembolism for users of oral contraceptives with desogestrel was 2.2 (1.7 to 3.0), with gestodene was 2.1 (1.6 to 2.8), and with drospirenone was 2.1 (1.6 to 2.8). The risk of confirmed venous thromboembolism was not increased with use of progestogen only pills or hormone releasing intrauterine devices. If oral contraceptives with desogestrel, gestodene, or drospirenone are anticipated to increase the risk of venous thromboembolism sixfold and those with levonorgestrel threefold, and the absolute risk of venous thromboembolism in current users of the former group is on average 10 per 10 000 women years, then 2000 women would need to shift from using oral contraceptives with desogestrel, gestodene, or drospirenone to those with levonorgestrel to prevent one event of venous thromboembolism in one year. ConclusionAfter adjustment for length of use, users of oral contraceptives with desogestrel, gestodene, or drospirenone were at least at twice the risk of venous thromboembolism compared with users of oral contraceptives with levonorgestrel. IntroductionThe influence of specific types of combined oral contraceptives on the risk of thrombotic events remains the most important safety issue for these products. Several studies have investigated the relation between combined oral contraceptives and venous thromboembolism, including newer large scale studies. [17][18][19] These new studies showed an increased risk of venous thromboembolism in current users of combined oral contraceptives and a decreasing risk by both time of use and decreasing oestrogen dose. RESEARCHResults on the significance of the type of progestogen differed. Ten studies reported an increased relative risk of venous thromboembolism among users of oral contraceptives with desogestrel or gestodene compared with those containing levonorgestrel, 1 2 4-7 9 13 17 18 a difference that was significant in eight of the...

Improved understanding of unsaturated fl ow and transport processes is limited by the lack of appropriate in situ measurement techniques. Th is study was conducted to determine whether two noninvasive cross-borehole geophysical methods combined could be used to estimate two important unsaturated zone transport parameters, namely the pore water velocity and longitudinal dispersivity. Cross-borehole electrical resistivity tomography and ground penetrating radar were used to estimate temporal and spatial variation of electrical resistivity and water content, respectively, during a 20-d forced infi ltration experiment. Th e resulting one-dimensional profi les and two-dimensional images of moisture content and electrical resistivity were subsequently combined to estimate solute tracer concentration. Th e results were used to analyze the downward migration and vertical spreading of water and tracer mass. Th e two geophysical methods provided independent estimates of soil moisture content and electrical resistivity that were spatially and temporally consistent. Th e observed changes in moisture content and electrical resistivity were, as a fi rst approximation, used in a one-dimensional moment analysis. Th e transport behavior was found to be very susceptible to layering of the subsurface. Even slight reductions in grain size apparently lead to fl ow barriers and associated lateral fl ow, resulting in tracer mass loss, reduced vertical pore water velocity, and increased longitudinal dispersivity. Synthetic data showed that the estimated unsaturated transport parameters (i.e., pore water velocity and longitudinal dispersivity) and the mass estimate were infl uenced by the selected electrical resistivity tomography inversion routine. In eff ect, an overprediction of all three parameters was observed.

Objective To assess the risk of venous thrombosis in current users of non-oral hormonal contraception.Design Historical national registry based cohort study. Setting Four national registries in Denmark.Participants All Danish non-pregnant women aged 15-49 (n=1 626 158), free of previous thrombotic disease or cancer, were followed from 2001 to 2010. Main outcome measuresIncidence rate of venous thrombosis in users of transdermal, vaginal, intrauterine, or subcutaneous hormonal contraception, relative risk of venous thrombosis compared with non-users, and rate ratios of venous thrombosis in current users of non-oral products compared with the standard reference oral contraceptive with levonorgestrel and 30-40 µg oestrogen. Diagnoses were confirmed by at least four weeks of anticoagulation therapy after the diagnosis.Results Within 9 429 128 woman years of observation, 5287 first ever venous thrombosis events were recorded, of which 3434 were confirmed. In non-users of hormonal contraception the incidence rate of confirmed events was 2.1 per 10 000 woman years. Compared with non-users of hormonal contraception, and after adjustment for age, calendar year, and education, the relative risk of confirmed venous thrombosis in users of transdermal combined contraceptive patches was 7.9 (95% confidence interval 3.5 to 17.7) and of the vaginal ring was 6.5 (4.7 to 8.9). The corresponding incidences per 10 000 exposure years were 9.7 and 7.8 events. The relative risk was increased in women who used subcutaneous implants (1.4, 0.6 to 3.4) but not in those who used the levonorgestrel intrauterine system (0.6, 0.4 to 0.8). Compared with users of combined oral contraceptives containing levonorgestrel, the adjusted relative risk of venous thrombosis in users of transdermal patches was 2.3 (1.0 to 5.2) and of the vaginal ring was 1.9 (1.3 to 2.7). ConclusionWomen who use transdermal patches or vaginal rings for contraception have a 7.9 and 6.5 times increased risk of confirmed venous thrombosis compared with non-users of hormonal contraception of the same age, corresponding to 9.7 and 7.8 events per 10 000 exposure years. The risk was slightly increased in women using subcutaneous implants but not in those using the levonorgestrel intrauterine system. IntroductionSeveral studies have assessed the risk of venous thrombosis in women using oral contraceptives.1-10 However, none has assessed the risk in women using subcutaneous hormonal implants. A recent study reported a 48% higher risk of venous thrombosis in women using a vaginal ring compared with those using combined oral contraceptives containing levonorgestrel, 11 and a few studies have reported the risk in women using a transdermal combined contraceptive patch, although the results were conflicting. 12-16Using a historical national registry based cohort study design, we assessed the absolute and relative risk of venous thrombosis in Danish women using non-oral hormonal contraception. MethodsInformation on the four national data sources that provided information for th...

HYDROGEOPHYSICSCross-borehole geophysical data can provide valuable information concerning hydrologic properties of the unsaturated zone. Such data are most often used sequentially, where images of soil physical properties are obtained through numerical inversion and then converted to hydrologic state properties using petrophysical relationships. If not accounted for, inversion artifacts are transferred to the resulting hydrologic images. We propose a framework in which multiple geophysical data sets can be incorporated using an integrated data fusion approach. Th e geophysical data collected are integrated in a forward modeling approach to evaluate a series of plausible hydrologic models. Th e approach permits an evaluation of the sensitivity of geophysical data for constraining hydrologic model parameters. We illustrate the approach using geophysical data collected during a dual water and solute tracer experiment in the unsaturated zone. Cross-borehole ground penetrating radar and electrical resistivity tomography, measuring electromagnetic travel time and electrical transfer resistances, respectively, were collected during a 20-d period. As a fi rst approximation, one-dimensional fl ow was considered and three models (one, two, and fi ve layers) of the subsurface were evaluated. Th e fi ve-layered model was found to be the only model capable of mimicking the infi ltration pattern satisfactorily. Th e results showed that only the hydraulic conductivity and one of the parameters (empirical parameter n) describing the soil moisture release curve for three of the fi ve layers could be constrained by the data, illustrating the nonuniqueness of the problem. Th e data fusion approach proved, however, that application of multiple geophysical methods may reduce hydraulic parameter uncertainty.

Sea‐level rise has been related to global warming. The modern system on the northern coast of Anholt, Denmark, may well be analogous to other beach ridge systems formed in microtidal regimes and our results should have impact on estimation of past sea‐level variation. Ground‐penetrating radar data collected across the modern (<30 years old) berm, beach ridge and swale deposits resolve downlapping reflections interpreted to mark sea level at the time of deposition. Existing time series of sea‐level data constrain actual sea‐level variation. Nineteen readings of sea‐level markers made along our profile fluctuate within −0.42 and 0.57 m above present mean sea level, consistent with 95% of the sea‐level data. These fluctuations reflect tidal effects and meteorological conditions. Main data uncertainties are well‐known and the sea‐level markers may be identified with a high degree of confidence.

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Changes in relative sea-level (RSL) during the Holocene are reconstructed based on ground-penetrating radar (GPR) data collected across a raised beach ridge system on the island of Samsø, Denmark. The internal architecture of the beach ridge and swale deposits is divided into characteristic radar facies. We identify downlap points interpreted to mark the transition from the beachface to the upper shoreface and, thus, sea-level at the time of deposition. This new data set shows that beach steps can be preserved and resolved in GPR reflection data. This is important, as downlap points identified at the base of the beach steps should be corrected for beach step height in order to be used as a marker of sea-level. Identification of beach steps in combination with observed changes in dips of the interpreted beachface reflections can give information about changes in the morphodynamic conditions of beach ridge progradation through time. The vertical levels of identified downlap points are combined with an age model based on optically stimulated luminescencedated samples to reconstruct RSL for the past c. 5000 years. Overall, the reconstruction shows that the period between c. 4800 and 3800 yr BP was characterized by relatively high RSL values around 2.3 m above DVR90 (Danish Vertical Reference 1990). A marked decrease in RSL of c. 1.3 m occurred between c. 3800 and 3600 yr BP at a rate of c. 5 mm/yr. After c. 3500 yr BP, the RSL curve shows a gradual decrease at a rate of c. 0.6 mm/yr.

Geological studies of past and present sea level rely on valid and robust features marking sea level in geological sections. Present sea-level markers around the upper shoreface to beachface transition are detected in a beach-ridge plain formed in a microtidal regime. These sea-level markers identify specific relative sea levels at the time of formation. Ground-penetrating radar (GPR) data collected across the youngest part of the beach-ridge system of Feddet, Denmark are compared with independent coastal morphological and sedimentological data of the active strand plain and interpreted in relation to sea-level data. The data show consistency between dip values of the present beachface and upper shoreface compared with dip values of interpreted beachface and upper shoreface GPR reflections. A clear change in dip value is observed between beachface and upper shoreface deposits in both data sets. Within few centimetres, this break point coincides with actual sea level and is interpreted to correspond to downlap points observed in the GPR reflection data. Furthermore, our observations may indicate that downlap points of deposits, formed under both relatively high and low water levels, are preserved and may be identified in GPR reflection data. Downlap points identified in GPR data across microtidal beach-ridge systems from other localities can also constitute markers of palaeo-sea level at the time of deposition. Records of these sea-level markers can be used to reconstruct the local relative sea-level history during the Holocene.