Quantifying and Reducing Uncertainty in Estimated Microcystin Concentrations from the ELISA Method.

We discuss the uncertainty associated with a commonly used method for measuring the concentration of microcystin, a group of toxins associated with cyanobacterial blooms. Such uncertainty is rarely reported and accounted for in important drinking water management decisions. Using monitoring data from Ohio Environmental Protection Agency and from City of Toledo, we document the sources of measurement uncertainty and recommend a Bayesian hierarchical modeling approach for reducing the measurement uncertainty. Our analysis suggests that (1) much of the uncertainty is a result of the highly uncertain "standard curve" developed during each test and (2) the uncertainty can be reduced by pooling raw test data from multiple tests. Based on these results, we suggest that estimation uncertainty can be effectively reduced through the effort of either (1) regional regulatory agencies by sharing and combining raw test data from regularly scheduled microcystin monitoring program or (2) the manufacturer of the testing kit by conducting additional tests as part of an effort to improve the testing kit.

Physical activity among older people with sight loss: a qualitative research study to inform policy and practice.

OBJECTIVES: To investigate the ways in which participation in physical activity is prevented or facilitated among older people with acquired sight loss later in life. STUDY DESIGN: Qualitative research. METHODS: Interviews were conducted with 48 visually impaired adults age 60+ years, recruited from a range of settings including local sight loss organisations and via talking newspaper advertisements. Visual impairment was defined by self-report. Data was analysed using a thematic analysis. This research represents a first step toward the development of empirically based practical suggestions for decision-makers and health professionals in terms of supporting - when required - visually impaired older adults participation in physical activity. RESULTS: Six themes were identified that captured why physical activity was prevented or facilitated: disabling environments; organisational opportunities; transport; lack of information; confidence, fear and personal safety; and exercise as medicine. CONCLUSIONS: Recommendations for policy change need to be focused at the societal level. This includes developing more accessible and inclusive environments and providing meaningful information about physical activity to older adults with a visual impairment, and visual impairment in older age to physical activity providers.

A scale to monitor progression and treatment of mitochondrial disease in children.

Mitochondrial diseases affect all age groups, but those with childhood onset often seem to experience the greatest burden of disability. In some paediatric patients this can be explained by a cumulative disability acquired over many years. In others, additional factors, including the nature and severity of the molecular defect, must be considered. To date, no large-scale studies have attempted to document the natural history of paediatric mitochondrial disease. This is in part at least, because no assessment tool has been available to plot the temporal course of a disease with such a diverse clinical spectrum. This paper describes how a practical and semi-quantitative rating scale has been devised for children with mitochondrial disease, the Newcastle paediatric mitochondrial disease scale (NPMDS). The scale is multi-dimensional and reproducible, offering a tool through which mitochondrial disease progression can be objectively monitored. We anticipate that use of this tool will facilitate both longitudinal natural history studies and the assessment of future therapeutic interventions.

Mitochondrial disease in adults: a scale to monitor progression and treatment.

The natural history of mitochondrial diseases is poorly understood, limiting our ability to offer prognostic advice to patients or to evaluate therapy. One major obstacle to improving our understanding is the lack of a clinical rating scale to monitor the extensive clinical spectrum of mitochondrial disease. In this article, the authors describe the development and validation of a practical and semiquantitative rating scale, the Newcastle Mitochondrial Disease Adult Scale.

Weight loss after extended gastric bypass.

BACKGROUND: Gastric bypass (GBP) is the most effective method for controlling morbid obesity. Previously we showed that extending the length of the Roux limb increased weight loss. We have done over 400 obesity operations during the past 20 years. The current study consists of patients from the last 10 years of our experience and compares short to extended Roux-en-Y GBP. METHODS: Data from all patients operated at the Ottawa General Obesity Clinic were entered into a database on an ongoing basis, and those from the past 10 years were analyzed. All patients had standardized preoperative investigations and postoperative follow-up. Details of these and of the operative technique are provided in the manuscript. RESULTS: The preoperative weight and BMI were 129 +/- 2 kg, and 46 +/- 2 kg/m2, respectively. The mean weight loss prior to surgery was -2 +/- 21 kg. The results were classified, by percentage weight loss as: 'excellent' = > 35%; 'good' = 25-34%; 'poor' = 15-24%; and 'failure' = < 15%. Sixty-five patients (69%) were available for 2-year follow-up. At this time, mean percentage weight loss was 34 +/- 2 versus 40 +/- 1 for the short Roux (45-135 cm) and long Roux (180-225 cm) groups, respectively (P < 0.01). There were no deaths, leaks, splenectomies or intra-abdominal infections. The incidence of hernia and/or reoperation for bowel obstruction was 35/121 or 29%. The overall incidence of diarrhea was 16/121 (13%) and 6/121 (5%) at 12 and 24 months. Quality of life is significantly impaired in at least three of these patients, all with extended limbs. Major vitamin deficiencies, alterations in liver functions, or other metabolic complications did not occur. CONCLUSIONS: Gastric bypass is the procedure of choice for morbid obesity. Weight loss is marginally improved in proportion to the length of the Roux limb but at a risk of diarrhea, which occasionally may not manifest itself for 8 to 12 months. It is important that methods be devised to correct follow-up, incisional hernias and diarrhea.

Sexual behavior and serum levels of prolactin, testosterone, and estradiol in young and old rhesus males.

It has been suggested that increased prolactin levels may contribute to decreased libido in aging male primates. To test this hypothesis, the association of sexual performance and serum prolactin levels was determined in young (10 year) and old (25.7 year) male rhesus macaques. Old males displayed significantly lower levels of sexual behavior than young males but their serum prolactin levels were not significantly higher. The correlation between prolactin levels and different measures of sexual behavior also were not significant for either old or young males. These data suggest that elevations in prolactin levels do not significantly contribute to the age-related decline in sexual performance in rhesus males.

Heterogeneity in responses to cancer. Part II: Sexual responses.

Heterogeneity in psychosexual responses to disease-specific diagnosis is demonstrated for two groups of cancer patients with testis cancer and Hodgkin's disease who are comparable in prognosis and treatment intensity. The two groups of patients and their partners are shown to differ in their ability to recover from psychiatric problems associated with the diagnosis and/or treatment of cancer.

Heterogeneity in responses to cancer. Part I: Psychiatric symptoms.

Heterogeneity in psychiatric responses to disease specific diagnosis is demonstrated for two groups of cancer patients who are comparable in prognosis and treatment intensity. Implications of this heterogeneity are drawn for etiological study and for planning psychiatric interventions.

Sexual performance of old and young male rhesus macaques following treatment with GnRH.

GnRH has been reported to facilitate sexual performance in a number of species. To determine whether the same was true for rhesus monkeys we measured sexual behavior and serum levels of testosterone (T) and luteinizing hormone (LH) following control tests and after treatment with two doses of GnRH. In the first experiment, old intact (N = 11) and old T-implanted, castrated (N = 4) rhesus macaques were examined. Mean intromission rate of old intact males was significantly lower following treatment with 100 micrograms of GnRH than following control injections. Other measures of sexual behavior did not differ across treatments. There were no significant treatment effects among the old castrated males. The failure to facilitate sexual performance may have been due to the age of the males and not to the species under study. Thus, in a second experiment the effects of GnRH were examined in young rhesus males. Again, there was no facilitation of sexual performance. This cannot be accounted for by a failure of GnRH to produce a physiological response. For both old and young intact males serum levels of LH and T increased significantly after treatment with both doses of GnRH. LH but not T levels increased significantly in the T-implanted males.

The effect of human chorionic gonadotropin on serum levels of testosterone, estradiol, and sexual behavior in young and old rhesus males.

Sexual behavior and serum levels of testosterone (T) and estradiol (E) were examined in five young and six old rhesus males (Macaca mulatta) before and after the injection of 500 and 1000 IU of HCG. The serum levels of T and E increased in both young and old males after injection of either dose of HCG. Serum levels of T were significantly higher in young than in old males in the period following the last injection of 1000 IU of HCG. Old males had significantly higher levels of serum E during treatment with 1000 IU of HCG, but serum E levels in the two groups did not differ before or after treatment. Serum levels of T and E did not differ between the young and old males when injected with 500 IU of HCG. HCG had no effect on sexual performance and the differences in levels of sexual performance between the young and old males were not eliminated.

Apomorphine, deprenyl, and yohimbine fail to increase sexual behavior in rhesus males.

Various doses of apomorphine, deprenyl, and yohimbine were administered to old (20-26 years) rhesus males that had been sexually active when younger and to younger (6-17 years) males that were characteristically sexually sluggish. These neuropharmacological agents have been reported to increase sexual behavior in male rats. In Experiment 1, 10 old intact rhesus males were tested after injection of vehicle and apomorphine, and 6 old testosterone-treated castrated males were tested after treatment with deprenyl and yohimbine and the vehicles for each drug. In experiment 2, the 5 younger males were tested after treatment with each of the drugs and with the vehicles for each drug. There were a few minor changes in behavior associated with certain doses of each of the drugs and as many depressive as facilitative effects on sexual behavior. This suggests that there are basic differences between rats and rhesus macaques in the systems mediating sexual behavior.

Change of female partner and postejaculatory performance of young and old rhesus males.

This study was undertaken to determine whether a change of female partner following ejaculation would reduce the postejaculatory interval (PEI). The male subjects were seven old (mean age 22.4 years) and five young (mean age 12.2 years) rhesus males (Macaca mulatta). The female subjects were four ovariectomized females rendered sexually receptive by treatment with estradiol benzoate. Introduction of a different female following ejaculation significantly reduced the PEI and latency to a second ejaculation in both young and old males. However, a different female did not reduce latencies to preejaculatory levels. The potential for enhanced sexual performance was retained in old rhesus males.

Testosterone therapy in young and old rhesus males that display low levels of sexual activity.

Ten wild-born rhesus (Macaca mulatta) males (estimated age, 14-28 years) were given pair-tests with each of six sexually receptive females. Males that ejaculated in 50% or less of the tests (N = 5) were assigned to an experimental group and those that ejaculated in over 50% of the tests (N = 5) served as a control group. All of the males had typically ejaculated in over 80% of the pair tests given in the past. The experimental group was injected daily with testosterone propionate (TP, 1 mg/kg) and was given a pair-test twice each week for six weeks. The control group was injected daily with oil and given comparable tests with the same females. Treatment with TP did not increase level of performance, and differences between the groups, overall, showed little change. In a second experiment five wild-born males (three, 7-9 years; two, 17 years) whose previous sexual performance had characteristically been sluggish were given two pre- and two posttests with each of five receptive females. They were given the same TP treatment as were the males in the first experiment. Treatment with TP failed to improve performance.

Old age and sexual exhaustion in male rhesus macaques.

The capacity for multiple ejaculations was measured in three groups of rhesus macaques whose ages ranged from 9 to 30 years. Each male was given a test of sexual exhaustion with each of five ovariectomized, estrogen treated females. Sexual exhaustion was defined as a 45-min period without a mount when the males were paired with a female. None of the very old males (25-30 years, N = 4) achieved more than two ejaculations before reaching sexual exhaustion. Old males (19-20 years, N = 5) displayed as many as six ejaculations and fully adult (9-15 years, N = 5) males achieved a maximum of five ejaculations before meeting the criterion of sexual exhaustion. Although very old males mounted as often as younger males they achieved fewer intromissions and the latency to intromission and ejaculation was longer. Mean mount and ejaculation latencies and the postejaculatory interval increased after ejaculation in all age groups. The females were not equally attractive sexually to the males and very old males were especially selective, copulating with only three of the females.

Treatment of pregnant rhesus macaques with testosterone propionate: observations on its fate in the fetus.

Castrated male primates, unlike castrated male rodents, respond to exogenous estrogen by releasing gonadotropin. Although this disparity is unexplained, it may occur because the amount of testicular androgen secreted during a critical period for sexual differentiation is not sufficient to completely androgenize the anlagen of the central nervous system (CNS) in male primates. Therefore, male primates might be incompletely masculinized, and if fetal males were exposed to additional androgen during sexual development, they would no longer display the positive feedback to estrogen that usually characterizes females. Besides the development of mechanisms mediating the release of gonadotropins, questions about relationships between adult male sexual behaviors and the intensity of the androgen stimulus upon developing neural structures are of interest. We tested some of these possibilities by injecting androgen into 8 pregnant rhesus macaques from Days 40 through 50 of gestation, and we compared serum levels of testosterone (T), dihydrotestosterone (DHT), and androstenedione (delta 4) in the fetal circulation with that of 5 untreated control males. Fetal sera (both male and female) from treated pregnancies did not contain significantly greater quantities of T and DHT than sera of intact control males from untreated mothers. The maternal sera, however, contained large amounts of T (125.05 +/- 27.40 [SEM] ng/ml, n = 8) and significant elevations of DHT and delta 4 after treatment. The concentrations of delta 4 in the fetal circulation were significantly elevated (p less than 0.01) in treated fetuses compared to intact control males, probably due to the actions of the 17 beta-hydroxysteroid dehydrogenases in the placenta, the fetus, or both.(ABSTRACT TRUNCATED AT 250 WORDS)

Differences among ovariectomized female rhesus macaques in the display of sexual behavior without and with estradiol treatment.

Ovariectomized, estrogen-primed, adult female rhesus macaques were preselected for the display of high (HLP) and low (LLP) levels of sexual performance. Eight sexually vigorous adult males were selected as partners. For 13 consecutive days each month, females received 0, 2.5, 5.0, and 10.0 micrograms of estradiol benzoate (EB) and were tested on Days 12 and 13 of injection. Blood samples were taken before and on the last day of each of the four injection series, and serum levels of estradiol, progesterone, and testosterone were determined with a radioimmunoassay. The HLP females (n = 5) displayed higher levels of receptivity and proceptivity and received more mounts, intromissions, and ejaculations when tested without EB treatment than LLP females (n = 5) did when they were tested with 10.0 micrograms of EB. Female receptivity, proceptivity, and attractiveness cannot be explained by estrogen action alone. The effectiveness of estrogen is limited by the somatic characteristics of the individual on which it acts.

Aging and primate male sexual behavior.

Old male rhesus macaques display less sexual behavior than young and middle-aged males. The decrease in sexual activity occurs without a statistically significant decline in gonadal hormones or change in diurnal patterns of serum T, DHT, or LH. Levels of sexual activity are not increased by administering T to old intact males. However, the hormone is effective in increasing sexual behavior in old long-term-castrated males. Performance can be increased to levels observed in equally old untreated intact males. Readily detectable physical disabilities of old age have been observed to impair sexual performance, but the observed general decline in sexual activity cannot be accounted for by known physical disabilities. Novelty, as represented by a change in female partner or by a change in environment, has not increased sexual performance in old rhesus males. Only when old males were paired with empirically selected preferred females is their sexual behavior increased to levels displayed by young males. Drugs reported to increase levels of sexual behavior in rats have thus far been less effective in old rhesus males than powdered rhinoceros horn has been in man. The probable absence of a placebo effect in rhesus males should increase their usefulness as an animal model for the study of sexual behavior in aging men.

Threshold for behavioral response to testosterone in old castrated male rhesus macaques.

The sexual behaviors of old, intact (N = 5) and old, castrated (N = 6) rhesus macaque males were compared in six series of pair tests with receptive females. The castrated monkeys were tested when untreated and when given five doses of testosterone propionate (TP; 0.004, 0.016, 0.064, 0.256, and 1.024 mg/kg of body weight) in consecutive months. The serum testosterone (T) level was determined for each male before and after each series of tests. When untreated, none of the castrated males ejaculated, and yawning was significantly less in these monkeys than in intact males-no other behavioral measures differed significantly. Within 2 weeks of daily injections of 0.004 mg of TP/kg, two males ejaculated, and all differences in measures of ejaculation were eliminated. A third male ejaculated after 1 week of treatment with 0.016 mg of TP/kg. Yawning values did not differ during and after treatment with 0.064 mg of TP/kg. Although final mean serum T levels were six times higher in castrated (24.3 ng/ml) than in intact males (4.2 ng/ml), sexual performance levels did not exceed those of intact males.