When is it safe to switch from oral contraceptives to hormonal replacement therapy?

Women may continue to use oral contraceptives (OCs) into their 40's and 50's, but to date no method has been evaluated to ascertain their ovarian status, i.e., whether fertility and estrogen production have diminished sufficiently so they could be safely switched to hormonal replacement therapy. A group of 12 postmenopausal women who had been, for long periods of time, on a regimen of 3 back-to-back packages (i.e., 63 days on, 7 days off) of low-dose oral contraceptives have been studied. Secondly, a group of 9 perimenopausal women aged 36 to 47 were examined in the same manner. The third group consisted of early reproductive age women (arbitrarily divided into subsets aged 17-25 and 26-35 using low-dose OCs in the customary regimen) as normal controls. Blood samples were obtained on the last day of a pill cycle and at 7 days off the pill. In some menopausal women, blood samples were obtained at both 7 and 14 days off OCs. Serum was assayed by RIA for estradiol, FSH and LH. As expected in the young reproductive age women, estradiol levels increase at one week off the pill, together with a rebound in FSH and LH to follicular phase levels. In the perimenopausal group, there was a sharp distinction based on age. The women over 40 showed a more marked rise in FSH while those aged 36-40 showed a distinctly lesser response. Estradiol levels were variable, but tended to show some age grouping. Little diagnostic separation was observed for LH. In postmenopausal women, FSH levels were not always elevated at one week post-pill, and even in a second trial with sampling at one and two weeks off the OC, not all postmenopausal women showed a "menopausal" increase in FSH. The more uniform feature was that estradiol levels never increased above basal values. The study found that serum estradiol levels increase after a week off the pill in controls, but are unchanged at one and two weeks in the menopausal group. FSH levels rebound normally in reproductive age women and usually, but not always, increase substantially in postmenopausal women. After two weeks off OCs, an increased FSH and/or no change in basal estradiol levels is strong evidence that it is now safe (contraceptively speaking) to switch from OCs to standard hormone replacement regimens.     

Pain threshold values during periodontal probing: assessment of maxillary incisor and molar sites

Probing pain threshold (PPT) assessments were conducted in the facial and oral sulci of maxillary central incisors and first molars of 10 periodontally healthy adults. All subjects were systemically healthy, free of pain, and reported no current medication usage. A computer-linked electronic probe, modified to deliver steadily increasing forces up to 200 grams, was used to collect the data. The system contained a subject operated "off-switch" which, upon activation, signaled the computer to record the subject's PPT. Assessments of each subject's PPTs were conducted on 3 separate occasions at 7-day intervals. Results indicated that the facial sulci of the incisors were the most pain sensitive. They displayed a mean PPT of 50.9 +/- 26.6 grams. The oral sulci of the incisors exhibited a mean PPT of 76.5 +/- 45.2 grams. Facial and oral sulci of the molars evidenced mean PPT values of 102.6 +/- 52.1 grams and 113.5 +/- 51.3 grams, respectively. These data suggest that sulci associated with incisor teeth are nearly twice as pain sensitive as sulci associated with molar teeth. In addition, facial sulci are significantly more pain sensitive than oral sulci. Data did not indicate a visit effect nor a side-of-mouth effect on PPT values.     

Do cardiovascular risk factors explain the relation between socioeconomic status, risk of all-cause mortality, cardiovascular mortality, and acute myocardial infarction?

Much remains to be understood about how low socioeconomic status (SES) increases cardiovascular disease and mortality risk. Data from the Kuopio Ischemic Heart Disease Risk Factor Study (1984-1993) were used to estimate the associations between acute myocardial infarction and income, all-cause mortality, and cardiovascular mortality in a population-based sample of 2,272 Finnish men, with adjustment for 23 biologic, behavioral, psychologic, and social risk factors. Compared with the highest income quintile, those in the bottom quintile had age-adjusted relative hazards of 3.14 (95% confidence interval (CI) 1.77-5.56), 2.66 (95% CI 1.25-5.66), and 4.34 (95% CI 1.95-9.66) for all-cause mortality, cardiovascular mortality, and AMI, respectively. After adjustment for risk factors, the relative hazards for the same comparisons were 1.32 (95% CI 0.70-2.49), 0.70 (95% CI 0.29-1.69), and 2.83 (95% CI 1.14-7.00). In the lowest income quintile, adjustment for risk factors reduced the excess relative risk of all-cause mortality by 85%, that of cardiovascular mortality by 118%, and that of acute myocardial infarction by 45%. These data show how the association between SES and cardiovascular mortality and all-cause mortality is mediated by known risk factor pathways, but full "explanations" for these associations will need to encompass why these biologic, behavioral, psychologic, and social risk factors are differentially distributed by SES.     

Identification of anovulation and transient luteal function using a urinary pregnanediol-3-glucuronide ratio algorithm

The sensitivity and specificity of a urinary pregnanediol-3-glucuronide (PdG) ratio algorithm to identify anovulatory cycles was studied prospectively in two independent populations of women. Urinary hormone data from the first group was used to develop the algorithm, and data from the second group was used for its validation. PdG ratios were calculated by a cycles method in which daily PdG concentrations indexed by creatinine (CR) from cycle day 11 onward were divided by a baseline PdG (average PdG/Cr concentration for cycle days 6-10). In the interval method, daily PdG/CR concentrations from day 1 onward were divided by baseline PdG (lowest 5-day average of PdG/CR values throughout the collection period). Evaluation of the first study population (n = 6) resulted in cycles with PdG ratios > or = 3 for > or = 3 consecutive days being classified as ovulatory; otherwise they were anovulatory. The sensitivity and specificity of the PdG ratio algorithm to identify anovulatory cycles in the second population were 75% and 89.5%, respectively, for all cycles (n = 88); 50% and 88.3% for first cycles (n = 40) using the cycles method; 75% and 92.2%, respectively, for all cycles (n = 89); and 50% and 94.1% for first cycles (n = 40) using the interval method. The "gold standard" for anovulation was weekly serum samples < or = 2 ng/ml progesterone. The sensitivity values for all cycles and for the first cycle using both methods were underestimated because of apparent misclassification of cycles using serum progesterone due to infrequent blood collection. Blood collection more than once a week would have greatly improved the sensitivity and modestly improved the specificity of the algorithm. The PdG ratio algorithm provides an efficient approach for screening urine samples collected in epidemiologic studies of reproductive health in women.     

Prophylactic efficacy of tilmicosin for bovine respiratory tract disease

The prophylactic administration of injectable tilmicosin for pneumonia in weaned beef calves was investigated in 1,806 animals. Comparisons were made among calves receiving an "on-arrival" injection of tilmicosin, calves receiving a single injection of long-acting oxytetracycline, and calves receiving no prophylaxis. Morbidity and mortality attributable to pneumonia, morbidity and mortality attributable to all causes, and case fatality were significantly lower in the group of calves that received tilmicosin, compared with calves that received long-acting oxytetracycline and calves that received no prophylactic antibiotic. Mean time to initial pneumonia treatment was significantly extended in calves that received prophylaxis, compared with those that received no antibiotic on arrival at the feedlot. Calves that received tilmicosin gained significantly more weight than calves that received oxytetracycline. Calves that were not treated for pneumonia during the trial period gained significantly more weight than did those calves that were treated for pneumonia regardless of experimental group. The majority of mortalities were attributable to fibrinous pneumonia (31/34). Important bacterial isolates (Pasteurella spp, Haemophilus somnus, Actinomyces pyogenes) obtained at necropsy did not have resistance to tilmicosin in association with administration of tilmicosin as prophylaxis for pneumonia. However, bacterial resistance to trimethoprim/sulfonamide and to oxytetracycline were commonly found in these postmortem isolates.     

Structural interaction of natural and synthetic inhibitors with the venom metalloproteinase, atrolysin C (form d)

The structure of the metalloproteinase and hemorrhagic toxin atrolysin C form d (EC 3.4.24.42), from the venom of the western diamondback rattlesnake Crotalus atrox, has been determined to atomic resolution by x-ray crystallographic methods. This study illuminates the nature of inhibitor binding with natural (< Glu-Asn-Trp, where < Glu is pyroglutamic acid) and synthetic (SCH 47890) ligands. The primary specificity pocket is exceptionally deep; the nature of inhibitor and productive substrate binding is discussed. Insights gained from the study of these complexes facilitate the design of potential drugs to treat diseases where matrix metalloproteinases have been implicated, e.g., arthritis and tumor metastasis.     

TFAS (a tophat for all species): design and computer optimizationof a new electrostatic analyzer

TFAS (tophat for all species) is discussed. It is a 360° field-of-view electrostatic analyzer that can process particles of either charge simultaneously. The TFAS analyzer resembles two tophat analyzers placed hat to hat, but with the tophat plates removed and the tophat region shared in common by both analyzers. In the tophat region, deflection is by parallel plates, one with potential +V and the other with potential -V. A collimator allows particles to enter this parallel plate region and the particles are then deflected into the spherical deflection region of the analyzer. The TFAS has characteristics comparable to the spherical tophat analyzer. A mathematical analysis is presented showing the optimal dimensions selection for the TFAS analyzer, given a particular tophat angle. Raytracing simulations have been performed. Design curves showing various analyzer characteristics as a function of tophat angle are presented. The design curves are compared to similar curves already in the literature for the spherical tophat analyzer. Differences between the TFAS analyzer and the spherical tophat analyzer are summarized     

Multi-Fidelity High-Throughput Optimization of Electrical Conductivity in P3HT-CNT Composites

Combining high-throughput experiments with machine learning accelerates materials and process optimization toward user-specified target properties. In this study, a rapid machine learning-driven automated flow mixing setup with a high-throughput drop-casting system is introduced for thin film preparation, followed by fast characterization of proxy optical and target electrical properties that completes one cycle of learning with 160 unique samples in a single day, a > 10 ×  improvement relative to quantified, manual-controlled baseline. Regio-regular poly-3-hexylthiophene is combined with various types of carbon nanotubes, to identify the optimum composition and synthesis conditions to realize electrical conductivities as high as state-of-the-art 1000 S cm⁻¹. The results are subsequently verified and explained using offline high-fidelity experiments. Graph-based model selection strategies with classical regression that optimize among multi-fidelity noisy input-output measurements are introduced. These strategies present a robust machine-learning driven high-throughput experimental scheme that can be effectively applied to understand, optimize, and design new materials and composites.     

Near- and Far-Field Characterization of Planar mm-Wave Antenna Arrays with Waveguide-to-Microstrip Transition

We present the design and characterization of planar mm-wave patch antenna arrays with waveguide-to-microstrip transition using both near- and far-field methods. The arrays were designed for metrological assessment of error sources in antenna measurement. One antenna was designed for the automotive radar frequency range at 77 GHz, while another was designed for the frequency of 94 GHz, which is used, e.g., for imaging radar applications. In addition to the antennas, a simple transition from rectangular waveguide WR-10 to planar microstrip line on Rogers 3003? substrate has been designed based on probe coupling. For determination of the far-field radiation pattern of the antennas, we compare results from two different measurement methods to simulations. Both a far-field antenna measurement system and a planar near-field scanner with near-to-far-field transformation were used to determine the antenna diagrams. The fabricated antennas achieve a good matching and a good agreement between measured and simulated antenna diagrams. The results also show that the far-field scanner achieves more accurate measurement results with regard to simulations than the near-field scanner. The far-field antenna scanning system is built for metrological assessment and antenna calibration. The antennas are the first which were designed to be tested with the measurement system.