e., around the shoulder), and risk of radiation injury to nerves that are in direct contact with the BT catheters.

A group of practitioners with expertise and experience in sarcoma BT were appointed by the American Brachytherapy Society (ABS) Board of Directors to provide a consensus statement for the use of BT in STS. The previously published ABS guidelines were updated with a literature search, and the experts view on the state of the art was formulated. The evidence supporting BT as a component of the multidisciplinary management of sarcoma is described. Recommendations are made on radiation techniques and doses, and the expected tumor GSK269962 molecular weight control and complication rates are provided. This consensus statement was submitted to the ABS Board of Directors for approval before publication. Ideally, patients should be evaluated by a multidisciplinary sarcoma team, which FGFR inhibitor includes surgical, radiation and medical oncologists, radiologists, and pathologists with knowledge and experience in the management of sarcomas. Preoperative staging evaluations include careful examination of the affected body site for extent of disease and the functional status of the affected body structure followed by imaging of the tumor with MRI for pelvic, extremity, and truncal lesions and CT for abdominal and retroperitoneal lesions to determine Selleckchem Venetoclax the

radiologic extent of disease. Preoperative imaging delineates the gross disease and associated tissue edema, and it may reveal invasion into surrounding structures.

Identification of the relationship of the lesion to adjacent critical structures, such as bone, nerves, and blood vessels, can be used to plan the extent and nature of the surgery. It is equally important to consider whether skin, soft tissue, bone, or vascular grafting will be required to repair the surgical defect. Chest CT should be obtained to rule out lung metastasis, which is the most common site of distant spread; patients with low-grade T1 lesions can be adequately staged with a chest X-ray. CT of the abdomen and pelvis may be valuable for patients with extremity or truncal liposarcoma, epithelioid sarcoma, angiosarcoma, or leiomyosarcoma, which have a higher rate of extrapulmonary spread (11). PET/CT may be useful for histologies with a predilection for nodal metastases, including clear cell sarcoma, angiosarcoma, rhabdomyosarcoma, epithelioid sarcoma, and synovial sarcoma. MRI of the spine for patients with myxoid liposarcoma can also be considered (12). Detection of lung metastasis should prompt consideration of chemotherapy and possibly surgical resection depending on the number, location, size, and rapidity of progression [13], [14] and [15]. Metastectomy for non-pulmonary metastasis has also been reported [16], [17] and [18].

Darüber hinaus wiesen silbermarkierte histochemische Präparate keine Signale in den Körnerzellen auf. Die Autoren wiesen

darauf hin, dass mit der Silbermarkierungsmethode in diesen Präparaten nur das anorganische Hg2+ und nicht die Alkylverbindungen nachgewiesen werden können. In der Studie von Charleston et al. [110] wurden Affen über längere Zeit niedrigen Dosen von MeHg ausgesetzt. Die Ablagerung von anorganischem Quecksilber wurde mithilfe der oben erwähnten Silbermarkierungsmethode nachgewiesen. Die stärksten Ablagerungen wurden in Astrozyten und Mikroglia beobachtet, während selleck products in Neuronen nach 6 Monaten, wenn überhaupt, nur sehr geringe Ablagerungen erkennbar waren. Nach 12 Monaten Exposition wurden bei den Tieren auch einige Ablagerungen in Neuronen gefunden, die nach 18 Monaten noch weiter zunahmen. In allen Fällen wurden jedoch mehr Ablagerungen in den Gliazellen als in den Neuronen festgestellt. In einer weiteren Arbeit über dieselben Tiere [111] schlugen die Autoren vor, dass Hg2+ die proximale toxische Form von MeHg ist und seine Wirkung über Populationen von Astrozyten und Mikroglia entfaltet. Vahter et al. [112] wiesen darauf hin, dass die Latenzphase, die mit einer MeHg-Exposition see more verbunden ist, auf die langsame, über Monate hinweg erfolgende Produktion und Akkumulation von Hg2+ im Gehirn zurückgehen könnte. Weiss et al. [113] zufolge würde man jedoch erwarten, dass die Ablagerung von anorganischem

Hg bei stärkerer MeHg-Exposition schneller abläuft, so dass sich bei höherer Dosis eine kürzere Latenzphase ergeben sollte. Magos et al. [56] verglichen die Toxizität von Methyl- und Ethylquecksilber und bestimmten dabei auch die Freisetzung von Hg2+. Dabei fanden sie, dass Ethylquecksilber zur Produktion von mehr Hg2+ führt als MeHg, aber trotzdem weniger toxisch ist. Ihre Schlussfolgerungen sprechen daher gegen eine zentrale Rolle von Hg2+, wie sie von Vahter et al. [112] vorgeschlagen wurde. Burbacher et al. [114] berichteten über die Verteilung von Quecksilber bei Affenbabys,

Glutathione peroxidase denen Ethylquecksilber in Form von Thimerosal intramuskulär injiziert wurde, im Vergleich zu einer zweiten Gruppe von Affen, denen eine MeHg-Verbindung oral eingegeben wurde. In der Studie sollte der Impfplan für menschliche Neugeborene simuliert werden. Burbacher et al. [114] berichteten, dass der Gehalt an organischem Quecksilber im Gehirn der Affenbabys, die Thimerosal erhalten hatten, niedriger war als bei den Affen, die MeHg oral erhalten hatten. Damit bestätigten sie die Schlussfolgerungen, die Mago et al. [56] aus Untersuchungen am Rattenmodell gezogen hatten. Die Halbwertszeit im Gehirn (definiert als die Zeit, in der der Hg-Gehalt im Gehirn auf die Hälfte absinkt) unterschied sich ebenfalls. Die Clearance-Halbwertszeit von organischem Hg im Gehirn betrug im Mittel 58 Tage nach oraler Exposition gegenüber MeHg im Vergleich zu 14 Tagen nach Injektion von Ethylquecksilber.

The ANCDS also reviewed 21 studies addressing the effectiveness of external aids for memory compensation, using the key questions noted above.5 The most common type of external aid was a written memory notebook or daily planner (9 studies), while other studies evaluated various electronic devices. The authors

concluded that treatment to establish the use of external aids for memory compensation might be considered a Practice Guideline as a means of improving day-to-day functioning for people with brain injury. Finally, the ANCDS 6 conducted a systematic review and meta-analysis www.selleckchem.com/products/gsk-j4-hcl.html of 15 studies addressing interventions for executive functions after TBI. Ten of the studies (including 5 RCTs) utilized

metacognitive strategy instructions (eg, for self-monitoring and control of cognitive processes). These studies supported metacognitive strategy training to improve problem solving for personally relevant activities, based on significant effect sizes for activity and participation outcomes compared with control treatments. The review led to the recommendation of a practice standard for the use of metacognitive strategy training with young to middle-age adults with TBI in chronic stages of disability for difficulties with problem solving, planning, and organization. Two reviews were based directly on the task force’s earlier systematic reviews. One of these evaluated the methodologic click here quality of 53 comparative effectiveness

studies (32 RCTs and 21 observational studies) involving exclusively or primarily Palmatine participants with TBI.7 There were several high-quality studies that supported the effectiveness of interventions for attention, communication skills, executive functioning, and comprehensive-holistic rehabilitation after TBI, including improvements on participation outcomes. This analysis also noted the value of non-RCTs in providing evidence for the effectiveness of cognitive rehabilitation for people with TBI. Rohling et al8 conducted a meta-analytic reexamination of the task force’s prior systematic reviews. They found a small significant overall treatment effect that was directly attributable to cognitive rehabilitation, after controlling for improvements in nontreatment control groups. The meta-analyis revealed sufficient evidence for the effectiveness of attention training after TBI, language treatment for aphasia, and visuospatial treatment for neglect syndromes after stroke. Treatment effects were moderated by the targeted cognitive domain, time since injury, etiology, and age. Differing conclusions between this meta-analysis and the systematic reviews may reflect differences in methodology.

The fatty acid profile of the lipids extracted from the cakes was obtained. The central slices were dried according

to AACC method 44-15.02 (AACC, 2010), milled and the lipids extracted as described in AOAC method 922.06 (AOAC, 2000). The fatty acid methyl esters (FAMEs) were obtained according to method UNE 55-037-73 (AENOR, 1991) and their compositions determined by capillary gas chromatography (CGC 6890 System Plus, Agilent Technologies, Mississauga, Canada) with a flame ionisation detector (FID). The capillary column Epacadostat chemical structure was a DB–225 J&W 122-2232 – 50% cyanopropylphenyl-dimethylpolysiloxane one (Agilent Technologies, Mississauga, Canada) with the following dimensions: 30 m long, 0.25 mm inner diameter and 0.25 μm film. The

analytical conditions were: injector temperature 220 °C, detector temperature 220 °C; oven temperature 60 °C (1 min) programmed selleck compound to increase to 210 °C at a rate of 6 °C/min and maintained at this temperature for a further 20 min; carrier gas: N2-UAP; and make-up gas: N2-UAP. The individual FAMEs were identified using the Lipid Standard Sigma 189-1 (Sigma Chemical Co. Ltd., Poole, UK) and Supelco FAME-Mix C4-C24 18919-1 (Supelco Inc., Madrid, Spanish), and the results are expressed as the total fatty acid content (TFA). Sensory evaluation of the cakes, acceptance tests and the purchasing intention were conducted after 1 day of storage. The samples were evaluated by 40 untrained panellists in isolated booths under white light. The attributes of colour, flavour and texture were evaluated using a 9-point hedonic scale (Stone & Sidel, 1993), where 1 = disliked extremely and 9 = liked extremely, and the purchasing intention on a five point scale, where 1 = “would certainly not buy” and 5 = “would

certainly buy”. The samples were served monadically in a random order. Scores from 4 to 5 were considered as a positive purchasing intention. Response Casein kinase 1 surface methodology was used to analyse the technological characteristics of the cakes with WCF and HVF as the independent variables, and the specific volume, crumb colour parameters, moisture content and firmness after 1, 4 and 7 days of storage as the dependent variables (responses). The Statistica 5.0 program (Statsoft Inc., Tulsa, USA) was used for the analysis of variance (ANOVA) to obtain the mathematical models and to build the response surfaces (p < 0.05). Differences between the average values for moisture content and firmness during the storage period, and the nutritional and sensory results obtained for the cakes were assessed by ANOVA and the Tukey test (p < 0.05) using the same statistical programme. Table 2 shows the results obtained for the proximate composition of the wheat flour and WCF. When compared to wheat flour, WCF had higher protein, lipid and dietary fibre contents, showing that WCF is an important source of these components.

, 2002 and Matés et al., 2008). Redox active metals may undergo cycling reactions participating in the transfer of electrons between metals and substrates and therefore may play an important role in the maintenance of redox homeostasis, a phenomenon tightly linked with metal homeostasis (Lindeque et al., 2010). Disruption of metal homeostasis may lead uncontrolled metal-mediated formation

of deleterious free radicals participating in the modifications to DNA bases, enhanced lipid peroxidation, and altered calcium and sulphydryl homeostasis (Gutteridge, 1995 and Valko et al., 2007). Humans may be exposed to redox-inert elements such as cadmium and arsenic which have no known biological Navitoclax ic50 function and are even known to be toxic at low concentrations. In contaminated areas, exposure to these elements arises from a variety of natural sources, including air, drinking water Selleck Talazoparib and food. While redox active metals undergo redox-cycling reactions, for the group of redox-inert elements, the primary route for their toxicity and carcinogenicity is depletion of glutathione, bonding to sulphydryl groups of proteins and other mechansisms of action (Speisky et al., 2008, Sinicropi et al., 2010 and Peralta-Videa et al., 2009). All these aspects of metals acting in biological systems

Adenosine triphosphate make the purpose of this paper to provide an overview of the current state of knowledge of the following: the role of redox-active metals, namely iron, copper, chromium, cobalt and redox-inert metals cadmium and arsenic in the formation of reactive oxygen and nitrogen species and their involvement in the development of human disease and ageing.

A special attention is paid to the anti-inflammatory role of the redox-inert metal zinc. Iron occurs in the oxidation states +II and +III. The ferrous ions are soluble in biological fluids and generate in the presence of oxygen damaging hydroxyl radicals. The ferrous ions are unstable in aqueous media and tend to react with molecular oxygen to form ferric ions and superoxide anion radical. The oxidized form of iron is insoluble in water at neutral pH and precipitates in the form of ferric hydroxide (Jones-Lee and Lee, 2005). Paradoxically, despite the fact that both iron ions, ferrous and ferric are so inaccessible, iron is the key catalytic site of many of the enzymes and oxygen-transporting proteins in cells. Although iron is vital for life, it can be toxic when it is present in excess (Lee et al., 2006a). Iron homeostasis is a complex process, as there are many different proteins that respond not only to the total body burden of iron, but also to stimuli such as hypoxia, anemia and inflammation.

8–1.0 s/rot; beam pitch: 0.5625–0.9375) and reconstruction parameters were predefined for each type of CT scanner (see Appendix). Beam pitch is defined as the ratio of table feed per rotation to the collimation, where collimation is the product of slice-thickness and the number of slices in each rotation. Beam pitch was kept under 1.0 except for one CT scanner

(Somatom Plus 4 Volume Zoom). Field of View (FOV) was defined as 350 mm to cover both hip regions. In-plane spatial resolution of 0.625–0.652 mm and reconstructed slice thickness of 0.500–0.625 mm was adjusted according to CT scanner type (see Appendix). The CT values were converted to bone mineral scale by using a solid reference phantom, mTOR inhibitor B-MAS200 (Fujirebio Inc., Tokyo, Japan), containing hydroxyapatite (HA) at 0, 50, 100, 150, and 200 mg/cm3. For all of the CT data, a constant threshold value of 350 mg/cm3 was used to define the cortical bone. The MDCT scanners used in this study originally included four Asteion 4 scanners, one Aquilion 4 scanner,

and three Aquilion 16 scanners (Toshiba Medical Systems Corporation,Tochigi, Japan); one LightSpeed Ultra_8 scanner, and one LightSpeed Plus_4 scanner (GE-Yokogawa Medical,Tokyo,Japan); and one Somatom Plus 4 Volume Zoom scanner (Siemens, AG, Berlin and Munich, Germany). In two institutions, CT scanners were changed during the trial period (from Aquilion 16 to Aquilion 64, and from LightSpeed Plus_4 to LightSpeed Ultra_16); therefore, the pairs of CT data in 26 patients were obtained check details using different CT scanners. However, because the results of all patients did not differ from results excluding the 26 patients (data not shown), the results of all patients are presented in this article. Good linear correlations between the

CT values and HA concentrations were demonstrated (r = 0.996–0.999; p < 0.0002–0.05) in all CT scanners. Differences in CT values according to X-ray energy were corrected by using the reference phantom to convert CT values to HA equivalent values. However, it was necessary to confirm the longitudinal stability of the CT values of the threshold value used to define the cortical bone. For the rod containing 200 mg/cm3 HA equivalent, which was used as the threshold value to define the cortical region, there Ponatinib nmr was less than 0.01% difference between the baseline CT value and CT value at 144 weeks. The subjects were scanned in the supine position, with the reference phantom beneath the patient and placed so as to cover a region from the top of the acetabulum to 5 cm below the bottom of the lesser trochanter in each hip joint (average slice number was 298). Bolus bags were placed between the subject and the CT calibration phantom. Both feet were fixed using a custom-made adjuster for hip DXA, which kept the subject’s knees flat and the toes pointed inward.

These patients have problems in sustaining attention over minutes (e.g., Malhotra et al., 2009: Robertson et al., 1997) and increasing alertness ameliorates the lateralized symptoms (e.g., Chica et al., 2012; Degutis Nutlin-3a mouse and Van Vleet, 2010; Thimm et al., 2006; Robertson et al., 1998). Further, non-spatial attention capacity deficits in these patients affect conscious awareness for items across the visual field. Vuilleumier et al. (2008) examined

responses to background checkerboards in early visual cortex of neglect patients completing a task at fixation. When central task load was low, early visual cortex responded to the checkerboards on both sides. However, when central load was increased, responses to checkerboards presented to the left visual field were reduced or abolished (see also, Bonato et al. (2010); Peers

et al., 2006; Sarri et al., 2009). Russell et al. (2004) revealed that patients with damage to right parietal cortex, even without neglect, missed peripheral targets when they were required to complete a difficult task at fixation. Selleck AZD6244 Performance was particularly poor on the contralesional side but there was even loss of ipsilesional vision when central task demand was sufficiently high. In addition to spatial impairments in conscious awareness under high load, observers can suffer detection deficits over time. The ‘Attentional Blink’ (AB) paradigm is used to delineate temporal capacity limits to perception ( Raymond et al., 1992; Shapiro et al., 1994). Participants are presented with two targets embedded in a stream of rapidly presented items at fixation. Healthy young participants often fail Selleckchem Atezolizumab to detect the second target if it is presented within a short lag of the first (under ∼500 msec). The time taken to process the first target occupies capacity, rendering it briefly difficult to identify another target; indeed task load manipulations within the AB paradigm indicate that perception of the second target reflects current availability of attentional

resources (e.g., Elliott and Giesbrecht, 2010). Patients with visuospatial neglect have shown an extended ‘AB’, with a failure to report second targets over a much longer lag period (e.g., up to 1300 msec) (see Husain et al., 1997; Hillstrom et al., 2004; Rizzo et al., 2001). However, it is unclear whether such deficits can also be protracted spatially, particularly to the contralesional side, as previous studies have used centrally presented targets. Our first study aims to assess whether the spatial contralesional deficit for discriminating stimuli when performing a demanding central task extends temporally and impairs perception for a longer period. This potential attention-modulated loss of available visual field – over space and time – is also relevant to healthy ageing and our understanding of the impact of age-related decline on daily function.

That was not reflected in our data; during winter PS-341 mw and spring the daily mortality rate were the lowest, while increasing from spring to summer (about 0.80). However this was most likely caused by relatively low abundance of this species, meaning that effect of predation was negligible, and other processes like advective transport were more visible. Although the data obtained from this study are too scarce to draw any long-term conclusions, they seem to fit to the trends observed in other parts of the

Baltic Sea, mostly increase in standing stocks of Acartia spp. and T. longicornis and decrease of Pseudocalanus sp. decline ( Dippner et al., 2000, Möllmann and Köster, 2002, Möllmann et al., 2000, Möllmann et al., 2005 and Renz et al., 2007). The same effect was also observed in production rates of those species, especially Pseudocalanus sp. which had production rates observed in bay that were several times lower than that observed in Central Baltic ( Möllmann and Köster, 2002 and Renz et al., 2007). Results obtained in this investigation show higher mortality of Target Selective Inhibitor Library chemical structure major copepod taxa than it was observed in 1970s, 1980s and 1990s. As the growing trend in the Gulf of Gdańsk seems to be reflecting the situation in other parts of Baltic Sea this could be caused by increased predation of clupeid fish on zooplankton, and it is similar to the situation observed at the beginning of 1990s. This research

was carried out with the support of a grant from the Polish State Committee for Scientific Research (No. NN306 353239). “
“Intensification of human activities regarding new technologies, especially inventing new substances, progress in medicine and pharmaceutical industry and the extension

of needs in progressing civilization in general, results in increasing anthropogenic pressure on the natural environment. The release of large amounts of chemical substances to the environment poses currently one of the serious MG-132 clinical trial problems as neither their effects nor their distribution among the environment components is well recognized. Therefore, the assessment of the environmental status became the key issue at present in order to support appropriate decisions on measures aiming at reduction of the pressures and restoration of the undisturbed functioning of the ecosystem. The HELCOM Baltic Sea Action Plan (HELCOM, 2007) is an example of such a voluntary initiative of countries wishing to have back a healthy sea, and the Water Framework Directive (WFD) (Anon., 2000) and the Marine Strategy Framework Directive (MSFD) (Anon., 2008) are the examples of strong legal actions that bind countries to undertake measures aiming at protection of the marine environment. Nonetheless, the first stage in any counter-measure is the appropriate assessment of the current environmental status and comparison with certain reference status assumed as the desired one.

Potentially, this strategy would increase the SVR rate and protect against the emergence of viral resistance.

Avoiding interferon and ribavirin also would improve tolerability, perhaps increasing compliance, resulting in more effective therapy. The study presented here describes outcomes from 12 or 24 weeks of treatment with an interferon-free, Protein Tyrosine Kinase inhibitor ribavirin-free combination of daclatasvir, asunaprevir, and BMS-791325 in treatment-naive patients with HCV GT 1 infection. This open-label, randomized, phase 2a study recruited patients from 13 centers in the United States and France. Patients were enrolled and completed treatment from November 17, 2011, to March 5, 2013. The study was approved by appropriate institutional review boards and/or independent ethics committees, and was performed in accordance with the Declaration of Helsinki and Good Clinical Practice as defined by the International Conference on Harmonization and ethical principles of local regulatory requirements. All patients provided written informed consent. All authors had access to the study data and reviewed and approved the final manuscript. Inclusion criteria selleck inhibitor were age 18-70 years, chronic HCV GT 1 infection with RNA level of 105 IU/mL or greater, no previous HCV therapy (treatment-naive), and no evidence of cirrhosis (as documented

by markers of cirrhosis, FibroTest [BioPredictive, Paris, France] score <0.72 and aspartate aminotransferase:platelet ratio <2, or liver biopsy). Patients with a FibroTest or aspartate aminotransferase:platelet ratio score exceeding the threshold for study

inclusion were required to have a liver biopsy documenting the absence of cirrhosis. METAVIR category for each patient was derived from the FibroTest result based on the conversion on the manufacturer’s website. Exclusion criteria included Sitaxentan an alanine aminotransferase level that was 5× or more the upper limit of normal, total bilirubin level of 2 mg/dL or greater, direct bilirubin level greater than the upper limit of normal, international normalized ratio of 1.7 or greater, albumin level of 3.2 g/dL or less, hemoglobin level less than 11 g/dL for women and less than 12 g/dL for men, absolute neutrophil count less than 1.5 × 109 cells/L (or <1.2 × 109 cells/L for African American individuals), platelet count less than 90 × 109 cells/L, creatinine clearance less than 50 mL/min, and ineligibility for peginterferon alfa 2a or ribavirin if needed for treatment intensification (see later). Women of child-bearing potential were required to use at least 2 contraception methods. All randomized patients received daclatasvir (60 mg, orally, once daily), asunaprevir (200 mg, orally, twice daily), and BMS-791325 orally at either 75 or 150 mg twice daily. The dose selection of BMS-791325 was based on phase 1 antiviral activity and safety.

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 Palbociclib datasheet 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 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 Thiamet G (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.