Approximate Bayesian computation reveals the factors that influence genetic diversity and population structure of foxsnakes.

Contemporary geographical range and patterns of genetic diversity within species reflect complex interactions between multiple factors acting across spatial and temporal scales, and it is notoriously difficult to disentangle causation. Here, we quantify patterns of genetic diversity and genetic population structure using mitochondrial DNA sequences (101 individuals, cytochrome b) and microsatellites (816 individuals, 12 loci) and use Approximate Bayesian computation methods to test competing models of the demographic history of eastern and western foxsnakes. Our analyses indicate that post-glacial colonization and past population declines, probably caused by the infilling of deciduous forest and cooler temperatures since the mid-Holocene, largely underpin large-scale genetic patterns for foxsnakes. At finer geographical scales, our results point to more recent anthropogenic habitat loss as having accentuated genetic population structure by causing further declines and fragmentation.

A critical investigation of ISO 11948-2 and ISO 11948-1 for predicting the leakage performance of small disposable incontinence pads for lightly incontinent women.

ISO 11948-2--an international standard laboratory method developed to predict the leakage performance of small disposable pads for lightly incontinent women--was investigated. The repeatability and reproducibility (precision within and between laboratories, respectively) of two variants on the method were found to be poor. The coefficient of variation for each method variant in each laboratory (two laboratories ran each variant) was higher than 40% for about half the 12 products evaluated. Results differed by up to 94% between laboratories for a given product. The ability of the method to predict the leakage performance of pads was investigated by measuring correlations between the clinical evaluations of the 12 products, and technical evaluations using ISO 11948-2. Correlations were very weak (r < or= 0.487). Accordingly, it is recommended that 11948-2 is withdrawn. A second international standard method (ISO 11948-1)--developed for evaluating large pads, but sometimes used on small ones--was also investigated. Correlations between the clinical evaluations of the 12 products and technical evaluations using ISO 11948-1 were weak (r < or = 0.560). Accordingly, it is recommended that ISO 11948-1 is not used for evaluating small disposable bodyworn pads for women.

Treatment of advanced breast cancer with mitomycin C combined with vinblastine or vindesine.

Mitomycin C together with either vindesine or vinblastine was given to 48 patients with previously treated advanced breast cancer. Thirteen (35%) of the 37 evaluable patients had a complete (one patient) or partial (12 patients) response. Overall median duration of response was 189 days (range, 90-700 days). Fifteen patients received mitomycin C and vindesine with six responses (40%) and a median response duration of 247 days (range, 162-700 days). Twenty-two patients received mitomycin C and vinblastine with seven responses (32%) and median response duration of 164 days (range, 90-330 days). Response duration for patients treated with mitomycin C plus vindesine was longer than that associated with mitomycin C plus vinblastine (p = 0.09). Significant toxicity included myelosuppression and neurologic symptoms, but was uncommon (less than 10% of patients). Therefore, the combination of mitomycin C and a vinca alkaloid appears to be useful in far-advanced refractory breast cancer.

Cost of breast cancer treatment. A 4-year longitudinal study.

OBJECTIVE: To determine the longitudinal cost of the treatment of patients with breast cancer. METHODS: An analysis was performed of 200 women with 205 newly diagnosed breast cancers during 1989 in a health maintenance organization population (US Healthcare, Blue Bell, Pa). Medical records and claims data were analyzed for the total costs of medical care during the 4-year period after diagnosis. The costs over time were analyzed for clinical stage and use of mammography screening. RESULTS: The total costs of medical care during the 4-year period after diagnosis were strongly related to clinical stage at diagnosis, with higher total costs for patients with stages III to IV at diagnosis compared with patients with stages 0 to II at diagnosis. The cost for all stages of disease declined after years 1 to 2, with the exception of stage II, which increased slightly in years 3 to 4. The use of screening mammography was associated with a significant decrease in the cost of medical care during the 4-year study period. CONCLUSIONS: The goal of mammography screening programs should be to achieve downstaging to stages 0 to 1 to achieve reduction in breast cancer mortality and to reduce the overall consumption of health care resources for the treatment of breast cancer. These cost data should be considered within the framework of future cost-effective analysis for screening mammography programs.

Impact of organochlorine contamination on levels of sex hormones and external morphology of common snapping turtles (Chelydra serpentina serpentina) in Ontario, Canada.

Recent research has suggested that contaminants in the environment may influence sex differentiation and reproductive endocrine function in wildlife. Concentrations of organochlorine contaminants (total polychlorinated biphenyls, pesticides) were higher in the blood plasma of snapping turtles from contaminated sites than in those from reference sites. The ratio of the precloacal length to the posterior lobe of the plastron (PPR) is sexually dimorphic in snapping turtles. There were significant reductions in the PPR at three contaminated sites versus two reference sites. The magnitude of the response was such that a significantly higher proportion of PPRs of males from a contaminated site (Cootes Paradise) overlapped with those of females than PPRs of males from a reference site (Lake Sasajewun). Observers can incorrectly identify the sex of turtles at the contaminated site based on secondary sexual characteristics alone. Unlike the changes to the morphology, there were few changes in 17 beta-estradiol or testosterone levels, and where differences occurred, there was more variation among reference sites than between the reference and contaminated sites. Our results suggest that environmental contaminants may affect sexually dimorphic morphology in snapping turtles without affecting circulating testosterone or estrogen levels in the adults.

Practice management, health maintenance, and the use of computers in today's medical office.

It is clear that a successful medical practice needs a competent caring physician as well as office personnel who understand how to manage an office. The successful management of a practice helps achieve the goals that the physician and practice manager have established. This article has introduced ideas about how to manage and evaluate a practice. Adoption of some or all of these ideas helps provide more comprehensive and satisfying care for the physician and his or her patients.

Environmental contamination and developmental abnormalities in eggs and hatchlings of the common snapping turtle (Chelydra serpentina serpentina) from the Great Lakes-St Lawrence River basin (1989-1991).

During 1989-1991, we assessed developmental abnormalities in embryos and hatchlings from eggs of the common snapping turtle (Chelydra serpentina serpentina). Eggs were collected and artificially incubated from eight sites in Ontario, Canada and Akwesasne/New York, USA. In eggs from the same clutches we measured 20 organochlorine pesticides, 48 polychlorinated biphenyl (PCBs) congeners including 6 non-ortho PCBs, 8 polychlorinated dibenzodioxins (PCDDs), 14 polychlorinated dibenzofurans (PCDFs) and total mercury. We found a significant increase in abnormal development with increasing polychlorinated aromatic hydrocarbon exposure in eggs, particularly PCDD and PCDF concentrations. In contrast, the risk of abnormality was not significantly higher as toxic equivalent concentrations increased in eggs. We also found significant 7-ethoxyresorufin O-deethylase and Cytochrome P4501A responses in livers of hatchling turtles from Lake Ontario relative to hatchlings from a clean, inland site whereas we did not find any evidence of porphyria in the hatchlings from either site.

Effects of the protozoan parasite Sarcocystis rauschorum on open-field behaviour of its intermediate vertebrate host, Dicrostonyx richardsoni.

Behaviour and activity levels were measured in varying lemmings experimentally infected with the heteroxenous parasite, Sarcocystis rauschorum to test the hypothesis that the parasite alters behaviour of this intermediate host and thereby increases probability of transmission to the definitive host, the snowy owl (Nyctea scandiaca). Measures of short-term activity levels on a running wheel indicated no effect of the parasite, either directly, or indirectly as a result of illness. We observed behaviour of infected lemmings placed in an "open field" (arena). Lemmings would increase their susceptibility to predators if they spent more time away from cover, used crypsis (stationary postures) less, spent more time exploring (especially in unfamiliar areas), or responded inappropriately to threats from predators. We found that only exploratory activity showed significant change after infection. The frequency of exploratory activity increased and became disassociated from the usual fear response. This may increase the lemmings' susceptibility to aerial predation. The mechanism for this effect is unknown, but neurological lesions have been observed. The examination of the modes of transmission of the S. rauschorum parasite within lemming populations and of a possible fecundity compensation strategy adopted by the lemmings, and their relevance to population control, are suggested as areas for future study.

Ultrastructural development of the sarcocyst of Sarcocystis rauschorum (Apicomplexa: Sarcocystidae) in the varying lemming Dicrostonyx richardsoni.

The development of the sarcocyst of Sarcocystis rauschorum in its intermediate host was studied. Lemmings were orally administered sporocysts of S. rauschorum obtained from snowy owls (Nyctea scandiaca). Beginning at 9 days postinoculation (DPI) and at various intervals to 84 DPI, skeletal muscle tissue taken from the infected lemmings was examined by electron microscopy. At 9 DPI the sarcocysts contained few metrocytes and the cyst wall was flat. The metrocytes underwent endodyogeny, and within a few days the cyst wall of the rapidly growing sarcocyst developed numerous tubulovesicular invaginations into the electron-dense layer, and the wall had a few irregular infoldings. By 21 DPI, banana-shaped bradyzoites appeared, and by 84 DPI the mature cysts were filled with bradyzoites in groups subdivided by septa and by deep infoldings of the cyst wall. The fine structure of the wall remained simple throughout maturation, with no conspicuous invagination or protrusion. The sarcocyst produced in response to S. rauschorum is unlike those from many species of Sarcocystis, which have complex walls that change markedly as the sarcocysts mature; however, its simple appearance is similar to other species that have rodents as intermediate hosts and raptorial birds as definitive hosts.

How well does ISO 11948-1 (the Rothwell method) for measuring the absorption capacity of incontinence pads in the laboratory correlate with clinical pad performance.

The ability of ISO 11948-1 (the Rothwell method) to predict the leakage performance of disposable bodyworn pads for heavy urinary incontinence was investigated by measuring correlations between models based on clinical evaluations of 138 diapers and inserts (the two major design categories), and technical models based on their Rothwell absorption capacities and design features. Correlations were poorer than in the original 1993 study for the standard (r < or =0.87 compared with r < or =0.95), but still strong enough to help with purchasing choices. For a given Rothwell capacity, the leakage performance of diapers was far superior to inserts; for example, diapers containing 450 and 300 g of urine performed, as well as inserts containing 300 and 100 g, respectively. No evidence was found for any other design feature having a significant impact on leakage performance. The coefficient of variation for Rothwell capacity (a measure of product consistency) had significant impact on the leakage performance of diapers, but not inserts. The probability of diapers with the poorest consistency leaking exceeded that for the best by about 10 percentage points. Similarly, diapers were about 10 percentage points more likely to leak when used at night than during the day. Differences between day-time and night-time use of inserts were not studied.

Predicting the leakage performance of small bodyworn disposable incontinence pads using laboratory tests.

An international multi-centre project has been run to create an international standard for measuring the leakage performance of small, disposable incontinence pads for lightly incontinent women. One hundred and thirteen women tested batches of nine different incontinence pads of widely differing designs and noted the severity with which each individual used pad had leaked so that leakage performance could be determined as a function of urine weight. In addition, testers rated the overall leakage performance of each of the nine products on a five-point scale. These clinical data were compared with laboratory data from 153 different pad measurements, each of which was evaluated by seeing how well the data it yielded correlated with the clinical test data. A wetback test emerged as the clear winner. It usually predicted the clinical leakage performance of pads to an accuracy of +/- 10%. It involved applying 25 ml of 1% w/v saline to a pad and measuring how much escaped into a filter paper held against the wet pad for 1 min under a pressure of 1.5 kPa. Pads which released the least test fluid into the filter paper leaked least in the user tests. The method will be published as an ISO standard during 1997.

An investigation of the repeatability and reproducibility of ISO 11948-1 (the Rothwell method) for measuring the absorption capacity of incontinence pads.

The repeatability and reproducibility (precision within and between laboratories, respectively) of an international standard method (ISO 11948-1, the Rothwell method) for measuring the absorption capacity of incontinence pads was investigated. The 74 shaped disposable bodyworn insert pads for heavy incontinence on the UK market in spring 1997 were tested in three laboratories experienced in using the method, one in each of England, Spain and Sweden. Coefficients of variation (standard deviation as a proportion of the mean) for five repeats rarely exceeded 5% within any laboratory. However, there were systematic differences between laboratories: results from the Swedish and Spanish laboratories typically exceeded those from the English laboratory by 13% and 8%, respectively. The good repeatability suggests that the method is capable of adequate precision but the poor reproducibility implies that the instructions in the standard for building and/or using the test apparatus are inadequate, leaving too much room for interpretation. Having studied the data presented here and viewed videos of the apparatus in use in five laboratories (including the three contributing to this note) the ISO working group which wrote the original standard has identified several likely sources of imprecision and is now working to revise the standard to improve its reproducibility.

Disposable bedpads for incontinence: predicting their clinical leakage properties using laboratory tests.

A multi-centre project has been run to identify laboratory tests capable of predicting the leakage performance of disposable incontinence bedpads. Each of 95 subjects tested each of six products for a week in turn and reported whether or not they and/or their carers found the leakage performance of each product acceptable. In addition, carers noted the severity with which individual used bedpads had leaked so that, when they had been weighed, their leakage performance could be determined as a function of urine weight. These clinical data were compared with results from the 16 different laboratory tests used routinely for bedpad evaluation in three hospital laboratories. Each test was evaluated by seeing how well the data it yielded correlated with the clinical test data. No individual test was very successful at predicting the performance of bedpads when used as sole protection but a combination of an absorption capacity test and an absorption time test predicted the percentage of users/carers finding leakage performance acceptable, accurate to within +/- eight percentage points for all six test products. A different absorption capacity test proved most successful for bedpads used as back-up to body-worn products. It predicted the percentage of users/carers finding leakage performance acceptable, accurate to +/- five percentage points for all six products.

Pathogenesis of infection with Sarcocystis rauschorum (Apicomplexa) in experimentally infected varying lemmings (Dicrostonyx richardsoni).

This study describes the sequential formation of lesions associated with the endogenous development of Sarcocystis rauschorum (Apicomplexa: Sarcocystidae) in varying lemmings, Dicrostonyx richardsoni. Lethal doses of sporocysts (greater than 500) were orally administered to lemmings examined 1-6 days postinoculation (DPI) whereas sublethal doses were administered to lemmings examined subsequently. Transient necrosis and purulent inflammation, in association with precystic merogony, occurred in the liver by 4.5 DPI, peaked at 6 DPI and subsided beginning at 11 DPI with the liver returning to normal by 15 DPI. Cyst formation in skeletal and cardiac muscle was associated with purulent inflammation and sarcolemmal proliferation beginning at 9 DPI. These lesions persisted to 42 DPI. In addition, multifocal nonsuppurative meningoencephalitis was present in six of 11 infected lemmings examined between 11 and 15 DPI.

Neurobehavioral and psychosocial functioning of women exposed to high altitude in mountaineering.

The effects of chronic hypoxemia upon cognition and behavior were studied in women exposed to high altitude in mountaineering. Neuropsychological tests and psychosocial and physiological questionnaires were given to eight women before, during, and immediately after a Himalayan climb to 20,500 feet. Cognitive functioning remained relatively intact with only two significant decrements, complex abstract reasoning and word-finding ability. Significant changes were found on all psychosocial and physiological questionnaires. Feelings of acceptance of others and anxiety declined significantly. Physical symptoms were greatest during the first five days of ascent. Subjects' self-ratings of mental functioning were significantly better after the expedition than either before or during the climb. Self-assessments were correlated with emotions and physical symptoms, not with actual performances on the test battery. It is suggested that complex cognitive tasks and psychosocial functioning be studied in more detail as these were more influenced by exposure to high altitude in mountaineering.

Factors affecting incidence of infanticide and discrimination of related and unrelated neonates in male Mus musculus.

Infanticide by males was examined in two strains (C57B1 and DBA) of the house mouse (Mus musculus). Males that had contact with a female within the previous 2-3 weeks rarely committed infanticide when introduced to the home cage of a female and her 1-day-old neonates, even when the female and neonates were of a different strain and from a different colony. In contrast, 90% of C57B1 males that had no contact with a female for more than 7 weeks killed pups when placed in the female's home cage, and 60% killed when a 1-day-old pup was introduced to the male's home cage. No difference in levels of infanticide occurred when grouped males were compared to isolated males. These results indicate that infanticide is not dependent upon recognition of the pups or the female, but depends on the male's previous exposure to females. Infanticidal behavior is not directly determined by genetic relationship, but the factors that inhibit this behavior reduce the probability that a male will kill his own offspring.

Modelling sub-binomial variation in the frequency of sex combinations in litters of pigs.

In some samples of pig litters, the number of males per litter exhibits significant sub-binomial dispersion: there are fewer unisexual and more "sex-balanced" litters than expected under a binomial model. It is argued here that the explanation is that the sex of zygotes may be subject to hormonal control with the consequence that, within a litter, the zygotes do not all have the same probability of being male. This variation in probability is approximated by a quadratic function of the time during oestrus that a zygote is formed so as to parallel the variation in maternal hormone levels. Other explanations are examined briefly, but each seems to have serious weaknesses.

Contaminant residues in snapping turtle (Chelydra s. serpentina) eggs from the Great Lakes-St. Lawrence River basin (1999 to 2000).

To determine temporal and geographic variations of environmentally persistent pollutants, the concentrations of several contaminants were measured in snapping turtle eggs in 1999 and 2000. Contaminants included polychlorinated biphenyls (PCBs), non- ortho PCBs, polychlorinated dibenzodioxins and furans, organochlorine pesticides, and total mercury. Egg collection sites within the St. Lawrence Area of Concern (AOC) and the Territory of Akwesasne included Turtle Creek, Snye Marsh, and Raquette River. Additional contaminated sites were Gray's Creek (within the St. Lawrence AOC boundary), Coote's Paradise (Hamilton Harbour AOC), and the Territory of Walpole Island (St. Clair AOC). Reference sites were Lake Sasajewun, Algonquin Provincial Park in central Ontario, and in close proximity to the St. Lawrence Area AOC, Hoasic Creek and Cooper Marsh. Eggs from clutches collected from Akwesasne contained the highest concentrations of contaminants. Mean total PCB concentrations for Akwesasne clutches ranged from 1,900 to 61,000 ng/g wet weight (w.w.), which was 360 to 3,100 times higher than the mean concentrations at the reference sites. The high levels of contaminants in eggs, from sites within Akwesasne, were consistent with trends reported in the past and reflect the influence of the proximity of heavy industry. Current contaminant concentrations in clutches from Coote's Paradise are comparable with those recorded in 1989 and 1990 but are 200 to 800 times lower than concentrations reported in 1984 and 1988. Eggs from Lake Sasajewun contained relatively low contaminant levels, which is consistent with atmospheric deposition. Our results support that snapping turtles are good indicators of temporal and geographic contaminant trends.