Without any assumption on which of these parameters is the most influential on wave runup, a characteristic length

parameter selleck compound L∗L∗ can be introduced for the dimensional analysis. As three dependent potential energies can be considered (i.e., EPEP, EP+, EP-), a characteristic energy E∗E∗ is also introduced. The functional relationship between the independent variables L∗L∗, E∗E∗, ββ, ρρ, and g  , can be expressed as: equation(13) R=f(L∗,E∗,ρ,g).R=f(L∗,E∗,ρ,g).The beach slope parameter is a dimensionless quantity (and an invariant in the present experiments), therefore not included in (13). The Buckingham Pi theorem (Hughes, 1993) was applied to (13) and out of this analysis (see Charvet, 2012) two dimensionless groups, Π1Π1 and Π2Π2, were formed: equation(14a,b) Π1=RL∗,Π2=(L∗)4ρgE∗.The characteristic length scale L∗L∗ may be the flume width (ww), wave amplitude (a   or a-a-), height (HH), wavelength (LL), or water depth (hh). As the present experiments were carried out in two dimensions, w   can be taken as a unit width so the following equation applies here

to a number of combinations of three possible variables for L∗L∗. The functional relationship between the two groups can be expressed as: equation(15) RL∗=ΨL∗3ρgE∗.By plotting Π1Π1 against Π2Π2 for a sample of simple combinations of L∗L∗, we can see that the data www.selleckchem.com/HSP-90.html is best described by a power law ( Fig. 9). All the data was used in these graphs. The cases where the correlation was poor were discarded. Therefore, we infer the functional relationship to be of the form: equation(16) RL∗=KL∗3ρgE∗k,where K and k are coefficients empirically determined from the dataset. Regression analysis is necessary to identify

the forms of (16) that can give a satisfactory fit to the data by optimizing values of K and k. Moreover, the scatter plots in Fig. 9 show that a significant proportion of the data tends to be clustered for large values of the predictor variable, which confirms the need for it to be partitioned into different wave categories. The uncertainty associated with (16) is quantified using a regression analysis. Linear regression can be performed using the variables in (16) by writing it as: equation(17) logRL∗=logK+klogL∗3ρgE+ε.It is necessary to find the best estimates (i.e., unbiaised) for the Gefitinib regression coefficients of the model, thus minimize the uncertainty associated with the prediction. To do so, the total error between the response data and the predicted response is reduced (as described in Appendix B) and the non-violation of the relevant statistical assumptions is checked. More details on regression analysis methods can be found in Chatterjee and Hadi (2006). To capture potential differences in runup regime between long waves, very long waves, elevated waves and N-waves, the wave data is divided into different populations.

Patients in

areas in which subtype C is endemic have a high rate of the K65R mutation after receiving drug regimens based on stavudine or didanosine (ddI).26 Recent data selleck products suggests that the increased rate of K65R acquisition may be due to the differing subtype C RNA template with an increased tendency of the virus to pause events at codon 65.27 Although the B variant is the most prevalent subtype in Western countries more than 90% of patients with HIV-1 infection worldwide have non-subtype B viruses. It is possible that a higher proportion of non-subtype B virus infection was present in our cohort leading to an increased rate of development of K65R mutation. Previous use of ART regimens containing ddI or ABC has also been shown to lead to an increased rate of K65R at XTC/TDF failure. Although patients with a resistance test showing evidence of either the K65R or M184V mutation were excluded from our study patients were not required to have a resistance test at baseline and therefore it is possible

that we observed resistance from previous regimens. In our study no significant difference was found between choice of cytidine analogue and development of K65R mutation which is in accord with data from de Mendoza et al., who described a statistically significant association between co-prescription of both ddI and ABC with TDF and the development of K65R, but no association between selection of K65R and administration this website of other NRTIs.25 Development of K65R Histidine ammonia-lyase mutation was significantly associated with lower current CD4 count. Study 903 found a statistically significant association between the presence of low CD4 count at baseline and the development of resistance mutation, with a median baseline HIV RNA viral load and CD4 cell count of 246,000 copies/ml

and 24 cells/μl respectively in the two patients who developed the K65R mutation.24 However, Study 934 failed to demonstrate the emergence of K65R mutation despite a similar proportion of subjects with low baseline CD4 T-cell counts.18 To our knowledge, this is the first data suggesting a role for current rather than baseline CD4 cell count in favouring the development of K65R mutation. Further research is required to determine whether this represents a true association. Ongoing viral replication in patients receiving ART promotes the development of drug resistance mutations.27 As expected, the development of both resistance mutations was significantly associated with detectable HIV-1 viraemia (VL > 50 copies/ml). Detectable viraemia may also be a surrogate marker for non-adherence to treatment. Interestingly, we found that episodes of viraemia (VL > 50 copies/ml) amongst patients of black ethnicity were more likely to lead to the development of M184V mutation. A recent systematic review found race/ethnicity to be a significant predictor of virological failure, but this was not attributable to differing rates of resistant HIV-1 minority variants.

However, these studies are not fully comparable due to differences regarding doses and species and the time point when the modified diet was introduced. Further Ryan et al. housed their mice in cages made of polycarbonate and used water bottles also made of polycarbonate, which might have been sources of BPA contamination in the control groups masking subtle effects, though it was otherwise a very sound study. The above mentioned studies were carried out with rodents which are said to be poor models for BPA in humans due to different toxicokinetics. According to a study by Tominaga et al. using nonhuman primates; chimpanzees (Pantroglodytes verus) and cynomolgus monkeys (Macaca

fascicularis), there are differences also among different primate species. In rodents the BPA T½ is longer, primarily explained by enterohepatic

recirculation in rodents but not in primates. The conjugation Selleck isocitrate dehydrogenase inhibitor rate in the liver is faster in rodents than in primates, primarily explained by a higher hepatic blood flow-rate in rodents ( Tominaga et al., 2006). However, there seem to be no differences in the metabolites formed e.g. it is a question of rate and time and not in the fate of BPA. The calculated mean exposure in humans is well below the TDI, but there are still uncertainties about the exact sources of exposure. Further, based on the WHO report: “Joint FAO/WHO Expert Meeting to Review Toxicological and Health Aspects of Bisphenol A Summary Report” (http://www.who.int/foodsafety/chem/chemicals/BPA_Summary2010.pdf), the most sensitive individuals – newborn babies – are also the ones with highest exposure. learn more According to this report the highest estimated exposure occurs in infants 0–6 months of age who are fed with liquid formula out of PC bottles: 2.4 μg/kg bw per day (mean) and 4.5 μg/kg bw per day (95th percentile), which is very close to the lowest dose used in the present study. In children, teenagers and adults the mean exposure was <0.01–0.40 μg/kg bw per day. Prenatal exposure to BPA has been shown to increase expression of

lipogenic Amino acid genes and adipocyte size in rodents (Marmugi et al., 2012 and Somm et al., 2009). Studies on isolated cells have shown BPA to induce production of proinflammatory cytokines, such as IL-6 and TNF-alpha (Yamashita et al., 2005), and to induce expression of adipogenic transcription factors (Phrakonkham et al., 2008), including PPAR-gamma activation (Kwintkiewicz et al., 2010). How these in vitro findings relate to the present finding of an increase in liver fat infiltration in combined exposure to fructose and BPA is not understood. The above-mentioned study by Marmugi et al. further suggests that exposure to low BPA doses may influence de novo fatty acid synthesis and thereby contributing to hepatic steatosis in mice (Marmugi et al., 2012). Interestingly, fructose has also been pointed out as a possible contributor to similar effects on the liver by its interaction with the Glut5 receptor (Lustig, 2010).

The Bosphorus-Marmara-Dardanelles system connects the Black Sea with the EMB. The exchange through the Strait

of Messina is much smaller than that through the Sicily Channel and is therefore neglected. The present study will treat the Black Sea solely as river runoff with a salinity 18 PSU lower than that of the Mediterranean. The EMB will be regarded as a single natural basin with in- and outflows, and processes such as air-sea interaction, land-sea interaction (i.e. river runoff), diapycnal mixing, overturning circulation (i.e. Atlantic water inflows, intermediate and deep water formation), exchange through the Sicily Channel and brackish water find more outflow from the Black Sea will be emphasized. The River Nile and Black Sea play important roles in changing the freshwater content of the EMB. The model will be driven by available meteorological and hydrological data and validated using available oceanographic observations. Based on the calculations, conclusions will be drawn

regarding the water (salinity) and heat (temperature) balances. The thermohaline water structure in the Eastern Mediterranean is an important climatic issue, as its changes may affect marine systems through changes in deep water formation, current systems and sea level variations. Freshwater input to the EMB mixes with sea surface water and surface water flows from the Western Mediterranean Basin through the

Sicily Channel. The outflow of water over the Sicily Channel sill (Figure 2b, page 205) is responsible see more for water loss from the EMB. The negative value of net precipitation Mirabegron (precipitation P minus evaporation E) influences the salinity balance. In the winter, because of evaporation and heat loss, the Levantine surface water may become dense enough to form Levantine intermediate-depth water (200–500 m) or Levantine deep water. However, deep water forms only occasionally. Roether & Schlitzer (1991) demonstrated that the average deep water formation rate in the EMB is approximately 0.3 × 106 m3 s− 1. Malanotte-Rizzoli et al. (1999) found that deep water formation takes place in the Adriatic, Aegean and Levantine sub-basins. Zervakis et al. (2000) demonstrated that the enhanced negative water balance of the Eastern Mediterranean leads to a new source of deep water formation, especially in the Aegean Sea. Béranger et al. (2002) investigated the mean inflow to the EMB through the Sicily Channel using numerical modelling. They estimated that the mean inflow through the Channel was approximately 1.05 ± 0.35 × 106 m3 s− 1 over a 13-year period. Stansfield et al. (2002) estimated the surface flow to the Eastern basin using observations from conductivity-temperature-depth (CTD) data. They found a surface flow of Atlantic water (AW) origin flowing through the Sicily Channel above a depth of 150 m.

Evans Blue dye (EBD) was used as an in vivo marker of myofiber damage (Hamer et al., 2002; Salimena et al., 2004). Briefly, 100 ml EBD (Sigma, MO, USA) dissolved in phosphate-buffered saline (PBS; 0.15 M NaCl, 10 mM phosphate buffer, pH 7,0), sterilized by filtration through 0.2 mm membrane

(Millipore Corp, MA, USA) then injected intraperitoneally (1 mg EBD/10 g body weight). Mice were killed 24 h later, muscles were snap frozen in OCT (Tissue-TEK; Elkhard, IN, USA), and 5 μm thick frozen sections fixed in acetone for 2 min, air-dried, quick-dipped in xylene and GDC-0980 supplier mounted with Enthelam (Merck, Damstadt, German). High definition whole area images of all cross-sections from each mouse at a time point were obtained from individual photomicrographs with a microdigital camera mounted on a Zeiss Axioplan microscope (Zeiss, Oberkochen, Germany) using a 10× objective and observed under bright field and fluorescence optics. Gastrocnemius muscles were embedded in OCT (Tissue-TEK; Dasatinib supplier Elkhard, IN, USA) and frozen in isopentane alcohol submerged in liquid nitrogen. 5 μm thick frozen sections were placed on poly-l-lysine (Sigma, St. Louis, Missouri) pre-coated slides and allowed to dry at room temperature for 4 h before staining. Hematoxylin-eosin

(Merck, Darmstadt, Germany) was used to verify morphological alterations and syrius red staining to detect collagen deposition. Captured images from three different levels of all cross-sections at each time point were acquired with a microdigital camera mounted on a Zeiss Axioplan microscope (Zeiss, Oberkochen, Germany) using a 20× objective. Images were mounted with Photomerge Adobe Photoshop CS3 software. Total surface area and areas occupied by injury and collagen deposition were determined with Image-Pro 4.5 (Media Cybernetics, Inc.). Results are expressed as percentage of total area in each cross-section. 5 μm,

spaced 500 μm cryostat cross-sections were mounted on poly-l-lysine pre-coated slides, fixed in acetone (−20 °C), blocked for endogenous peroxidase activity with 3% hydrogen peroxide in PBS for 30 min, and for unspecific antigens with PBS containing 5% of goat serum. Sections were then incubated Oxymatrine at room temperature for 60 min with primary monoclonal rat IgG anti-F4/80 (clone CI; A3-1; Serotec, Oxford, UK) at a 1:50 dilution in phosphate-buffered saline (PBS) followed by incubation with streptavidin–peroxidase complex (1:300; Sigma) and further washed with PBS. Enzyme activity was revealed with aminoethyl-carbazole (Sigma) in the presence of hydrogen peroxide. All sections were lightly counter-stained with Mayer’s hematoxylin (Sigma). Percentage of F4/80 positive areas in the injury foci was determined with Image-pro Plus 4.5 software (Media Cybernetics Inc., Silver Spring, MD). It included three mice per experimental group and analyzed six frozen sections per animal.

The extent of clot lysis was automatically measured by means of light absorbance at a wavelength of 412 nm using a spectrometer before and after thrombolytic treatment. This method allowed the

researchers to measure automatically a total of 200 positions within minutes, representing a throughput about 100 times as large as that of conventional methods. Magnetic resonance-guided focused ultrasound (MRgFUS) is a novel method for optimizing US treatment. In general, magnetic resonance imaging (MRI) enables the adjustment of the US beam, based on differences in temperature measurements in the targeted parenchyma. For the purpose of sonothrombolysis, preliminary steps have involved using in vitro models with human skull and porcine brain. In future, it may be possible to detect the thrombus within the vessel, to focus the US beam on this Selleck Cyclopamine target, and make corrections to the US beam

so as to avoid side effects of US caused by distortion and shifting of the human skull [29] and [30]. Another way of enhancing the effect of sonothrombolysis involves the use of microspheres. Commercially manufactured ultrasonic contrast amplifiers have been used in several studies: SonoVue®, which consists of sulfur hexafluoride-filled microbubbles of phospholipids, and Levovist®, a granulate of galactose and palmitic acid, which binds to micrometer-sized air bubbles. Following IV injection, they Inhibitor Library solubility dmso take energy on under influence of US, and by oscillation or rupture, this energy is released again, which reinforces the US effectiveness. Various experiments have shown the effectiveness of this method without an increase in the intracranial bleeding rate, which has been demonstrated in vivo. Molina et al. [31] showed an improvement by intermittent bolus injection of Levovist® in addition to tPA treatment plus 2-h insonation with TCD monitoring. A similar study was conducted

by Perren et al. [32] in which patients who had suffered from an MCA stroke underwent IV rtPA thrombolysis and 2-MHz TCCS monitoring for 1 h with SonoVue®, resulting in clinical improvement in these patients. No additional intracranial bleedings were noted in these studies. In the transcranial ultrasound in clinical sonothrombolysis Niclosamide (TUCSON) randomized clinical trial, intravenously applied microspheres, which had been developed for the purpose of strengthening the effect of sonothrombolysis, were clinically tested [5]. This dose-escalation study of microspheres showed increased bleeding in the second dose tier, prompting the sponsor of the study to discontinue this approach. In vivo molecular imaging of the human thrombus can be carried out with microspheres conjugated with abciximab, a glycoprotein IIb/IIIa receptor inhibitor that is involved in ligand targeting of the thrombus. In vitro experiments have shown that improved binding of microspheres to the clot enhances sonothrombolysis [33] and [34]. In their 2011 study, Shimizu et al.

11 The data are subject to quality checks and a practice’s data are only used when they are of high enough quality to be used in research, at these times the data are said to be “up to research standard.”12 The GPRD has been extensively validated for a wide range

of diagnoses, with a mean positive predictive value of 89%.13 Ethical approval Apitolisib ic50 for this study was obtained from the Independent Scientific Advisory Committee for Medicines and Healthcare products Regulatory Agency database research. Fifty-one percent of English practices in GPRD have consented to record level linkage of their population to Hospital Episodes Statistics. This records all hospital admissions from the population registered to one of the linked primary care practices contributing to the GPRD. For this study, the linked dataset was available between April 1, 1997 and August 31, 2010. We have

previously published the codes and methods used to define upper gastrointestinal bleeds in this study.14 In brief, we selected as exposed all patients with a first nonvariceal upper gastrointestinal bleed. A bleed was defined by a specific code for an upper gastrointestinal nonvariceal bleed in either primary or secondary care who had a supporting code in the linked dataset (defined as a likely symptom, cause, therapy, investigation, or outcome of upper gastrointestinal hemorrhage). Variceal bleeds or nonspecific gastrointestinal bleed codes with either a lower gastrointestinal diagnosis or procedure were excluded. Afatinib price Further exclusions were temporary patients (patients not registered permanently at a GPRD primary care practice, who might just be visiting the area of the practice briefly, and who are therefore Montelukast Sodium not part of the GPRD’s underlying

population), children younger than 16 years old, cases with invalid date codes, or cases outside the up-to-research-standard observed time periods. Patients were required to be registered with the primary care practice for at least 3 months before an upper gastrointestinal bleed event to avoid including prevalent cases that might have been coded at the initial registration consultation. Only the first event for each patient was included. We have previously demonstrated that this selection strategy minimizes selection bias in studies of upper GIB in these data.14 A secondary analysis was then stratified by whether the defining bleed code or supporting code specifically referred to a peptic ulcer (Read codes J11 to J14 or International Classification of Diseases, 10th Revision codes K25–K28). The Read codes had high positive predictive values (>95%) for peptic ulcers and upper gastrointestinal complications when validated in English primary care routine records. 15 and 16 Each case was age (±5 years) and sex matched without replacement to 5 controls selected randomly who were alive at the time of the gastrointestinal bleed and registered to the same primary care practice.

The upper bounds represent the levels determined for silty clays, and the lower bounds represent the levels determined for coarse sands, where all other sediment types modeled lie between these two boundaries.

The dark lines represent the mean values for the range of sediments modeled, and correspond to the values shown in Fig. 3. The areas of seafloor shown in Fig. 5A and B both have high levels of 137Cs recorded at the bases of vertical terrain features. The region in Fig. 5A, labeled A in Fig. 3 and Fig. 4, is an 8 m high southward facing feature of the terrain located 5.9 km from shore and 3.7 km north of F1NPP. While the levels of 137Cs on top of the feature average 65 ± 9 Bq/kg (where the range of values represents measurement uncertainty), the average level of 137Cs measured at its base within 320 m of the feature Selleckchem GDC0199 is 524 ± 63 Bq/kg, with a maximum value of 985 ± 118 Bq/kg in this patch. Another anomaly was mapped

a few 100 m further on from the feature. The patch is 70 m in length, and averages 651 ± 77 Bq/kg with a maximum 137Cs level of 1,432 ± 173 Bq/kg. The results show that the terrain strongly influences the level of 137Cs, with more than an order of magnitude difference in the levels measured on top and at the base of the feature. Similar observations were made for the seafloor shown in Fig. 5B, which is a 3.5 m high feature located 3.2 km east of F1NPP. This region serves as a boundary for the radiation levels, with the seafloor on the plant AZD1208 mouse side of the feature, 1.7–3.2 km

from the plant along this transect averaging 446 ± 62 Bq/kg, and the levels on the L-gulonolactone oxidase other side of the feature, 3.4–4.9 km from the plant yielding an average of 133 ± 17 Bq/kg. The level of 137Cs at the base of the feature has a maximum value of 2276 ± 266 Bq/kg, with an average of 1534 ± 175 Bq/kg over the 70 m long patch. The seafloor in Fig. 5C shows an anomaly in a depression located 10.3 km east and 0.7 km north of the F1NPP. The highest level of 137Cs in this patch is 1190 ± 136 Bq/kg, with an average of 508 ± 58 Bq/kg over the 105 m length of the anomaly measured along the transect. Here the size of the depression bounds the dimensions of the anomaly, and it is clear that features of the terrain influence not only the distribution, but also the size of the anomalies identified in this work. In addition to terrain related anomalies, anomalies have also been identified in areas with no noticeable features of the seafloor. The seafloor shown in Fig. 5D, located 1.6 km east of the F1NPP between 0.2 km and 2.2 km south of the plant, has particularly high levels of 137Cs averaging 528 ± 67 Bq/kg. The highest level of 137Cs recorded in this region is 40,152 ± 3998 Bq/kg, with two other locations nearby where the levels of 137Cs measured are >5000 Bq/kg.

Under physiological conditions, B2 receptor knockout mice (B2−/−) present normal development [9], renal hemodynamics and salt balance [2], [26] and [35]. Nevertheless, data regarding the effects of B2 receptor deletion on blood pressure regulation are controversial. Some authors have demonstrated that B2−/− are

normotensive [1], [2], [3], [11], [12], [26], [35], [37] and [39] while other groups observed a slight but significant increase in blood pressure levels [15], [16], [21] and [22]. Considering that both B1 and B2 receptors are located in the endothelium and in vascular smooth muscle cells [7] and [19], and that resistance vessels are the most important sites for determining peripheral vascular resistance [38], the present study BIBW2992 mw was addressed to investigate the vascular reactivity of mesenteric arterioles of B1−/− Selisistat mouse and B2−/− in response

to endothelium-dependent and -independent agonists. In parallel, plasma NO levels, vascular NO release and NOS activity in the mesenteric vessels were also analyzed in order to provide information about NO bioavailability in these mice strains. C57Bl/6 male knockout B1 (B1−/−), B2 (B2−/−) and wild type (WT) mice, aged 10–14 weeks were obtained from the breeding stock of Centro de Desenvolvimento de Modelos Experimentais para Medicina e Biologia (CEDEME – UNIFESP). Mice were kept in a temperature-controlled room on a 12 h light/day cycle, 60% humidity, standard mice chow and water ad libitum. In B1−/− and B2−/−, the absence of the kinins receptors was shown by undetectable level of mRNA encoding for the

B1 or B2 receptor, respectively, using a semi-quantitative RT-PCR technique. All procedures were approved and performed in accordance with the guidelines of the Ethics Committee of the UNIFESP (protocol number 0928/05), conformed with the Guide for the Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH Publication No. 85-23, revised 1996). Isolated mesenteric vascular beds were prepared as previously described for the rat preparation [24], with slight adaptations for the mouse. The mesenteric vascular bed was perfused with Krebs-Henseleit solution, pH 7.4, 37 °C, gassed with 95% O2 Tyrosine-protein kinase BLK and 5% CO2, at a constant rate of 2 mL/min using a peristaltic pump. Vascular responses were evaluated by changes in the perfusion pressure (mmHg) measured by a data acquisition system (PowerLab 8/S, ADInstruments Pty Ltda, Australia). To confirm the viability of tissues, preparations were perfused with KCl (90 mmol/L) added to the Krebs solution for 5 min. After 30 min of stabilization, increasing doses of norepinephrine (NE) (5–100 nmol), acetylcholine (ACh) (0.1–10 nmol) and sodium nitroprusside (SNP) (0.1–10 nmol) were injected in bolus, in a volume range of 30–100 μL, with a 3-min interval between each dose.

The Million Women Study

is a large prospective cohort study of women in the UK. Details of the design and methods of the study have been described elsewhere [11]. In short, 1.3 million women invited for breast cancer screening at National Health Service (NHS) clinics in England and Scotland were recruited into the study in 1996–2001 by completing a questionnaire, which included questions on anthropometry, physical activity, and other factors, and giving written find more consent to participate (see http://www.millionwomenstudy.org). Ethics approval was provided by the Oxford and Anglia Multi-Centre Research Ethics Committee. Each woman’s unique NHS identification number, together with other personal information, LBH589 datasheet was used to link to cause-specific information

on NHS hospital admission databases: Hospital Episodes Statistics for England, [12] and Scottish Morbidity Records in Scotland [13]. The databases include information both on inpatient (i.e. overnight) stays and day-case admissions (where women were admitted and discharged on the same day, e.g. for procedures such as the reduction of a fracture), but not on outpatient visits. Information on the date of diagnoses and procedures associated with each hospital admission were provided, coded to the World Health Organisation’s International Classification of Diseases, 9th and 10th revisions (ICD-9 and ICD-10) [14] for diagnoses and the Office of Population Censuses and Surveys’ classification of surgical operations and procedures, fourth revision (OPCS-4) [15] for procedures. Incident cases were defined as the first hospital record (day-case or overnight admission) of ankle fracture (824.0–824.9, ICD-9; S82.3, S82.5–S82.6, S82.8, ICD-10), of wrist fracture Cyclooxygenase (COX) (813.4, 813.5, 814.0–814.1 ICD-9; S52.5–S52.6, S62.0–S62.1, S62.8, ICD-10), or of hip fracture (820, ICD-9; S72.0–S72.2, ICD-10) occurring

after recruitment into the study. For the purposes of censoring at the first occurrence of any fracture (see below), all other fractures were defined as codes: 800.0, 800.5, 801.0, 801.5, 802, 803.0, 803.5, 804.0 804.5, 805, 807–829 (ICD-9) and M48.4, M80, M84.3, S02, S12, S22, S32, S42, S52, S62, S72, S82, S92, T02, T08, T10, T12, T14.2, X59.0 (ICD-10). Analyses were restricted to postmenopausal women: those who reported at baseline that they had experienced natural menopause (49%), or had undergone a bilateral oophorectomy (6%) were defined as postmenopausal. Women who were premenopausal, perimenopausal, or of unknown menopausal status at recruitment, were assumed to be postmenopausal after they reached the age of 55 years, as 96% of women in this cohort with a known age at natural menopause were postmenopausal by that age.