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Calibrating a molecular clock from phylogeographic data: moments and likelihood estimators.

We present moments and likelihood methods that estimate a DNA substitution rate from a group of closely related sister species pairs separated at an assumed time, and we test these methods with simulations. The methods also estimate ancestral population size and can test whether there is a significant difference among the ancestral population sizes of the sister species pairs. Estimates presented in the literature often ignore the ancestral coalescent prior to speciation and therefore should be biased upward. The simulations show that both methods yield accurate estimates given sample sizes of five or more species pairs and that better likelihood estimates are obtained if there is no significant difference among ancestral population sizes. The model presented here indicates that the larger than expected variation found in multitaxa datasets can be explained by variation in the ancestral coalescence and the Poisson mutation process. In this context, observed variation can often be accounted for by variation in ancestral population sizes rather than invoking variation in other parameters, such as divergence time or mutation rate. The methods are applied to data from two groups of species pairs (sea urchins and Alpheus snapping shrimp) that are thought to have separated by the rise of Panama three million years ago.

Animals↗

Floating patterns of metered dose inhalers.

As long as metered dose inhalers have existed, patients have sought a reliable method to determine if a given canister was still potent. Concerning beta agonists, the answer to this question may be lifesaving. Issues of compliance have made dating canisters or counting doses impractical. Likewise, previous claims of floating characteristics are unreliable. In tap water, we float-tested 13 commonly used inhalers three times each, observing variations as they were incrementally actuated, emptying their contents. One essential pattern was observed. Almost all prescription-size canisters sink when full; all float by the time one-third of their contents is gone. Orientation of prescription-size canisters changes in a distinct pattern especially near 90% depletion. Sample-size canisters showed some variance. Results suggest that the pharmaceutical industry should include individual floating characteristics as part of the package insert as they provide a reproducible means of gauging contents.

Administration, Inhalation↗

Variations in the subclavian-axillary arterial system.

OBJECTIVE: The objective of this study is to report on the subclavian axillary arterial system variations observed in the dissecting room. METHODS: The morphological study of 106 formalin fixed upper limbs of adult human cadavers of both sexes was carried out at human anatomy laboratory of College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia over a 5 year period, to observe the distribution pattern of the subclavian axillary arterial system. RESULTS: The arterial variations in the upper extremities are quite common and may occur at the level of the thoracic outlet, axilla, arm, cubital fossa and the hand. In the present study, the anomalous topographic pattern of the subclavian axillary arterial system was revealed in 7.5% of the cadavers, whereas 92.5% exhibited classical pattern of the regional arterial anatomy. The study showed: 1. An aberrant right subclavian artery arising from the arch of aorta, distal to the left subclavian artery. 2. A bilateral common subscapular-circumflex humeral trunk (3.8%) emerging from the 3rd part of the axillary artery (branching into the circumflex humeral and thoracodorsal arteries. 3. A bilateral thoracohumeral trunk arising from the 2nd part of the axillary artery (1.9%) and branching into the lateral thoracic, circumflex humeral, subscapular and thoracodorsal arteries. These anomalies were accompanied by anomalous insertion of flexor digitorum superficialis muscle, a bilateral digastric muscle formed by the abductor pollicis longus and brevis, and an anomalous formation of median nerve by 3 roots. CONCLUSION: The aberrant right subclavian artery associated with right non-recurrent laryngeal nerve and variant branching pattern of the axillary artery are of interest to anatomists, surgeons and radiologists and suggested that these anomalies must be evaluated pre-operatively.

Journal Article↗

Variations in the subclavian-axillary arterial system.

OBJECTIVE: The objective of this study is to report on the subclavian axillary arterial system variations observed in the dissecting room. METHODS: The morphological study of 106 formalin fixed upper limbs of adult human cadavers of both sexes was carried out at human anatomy laboratory of College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia over a 5 year period, to observe the distribution pattern of the subclavian axillary arterial system. RESULTS: The arterial variations in the upper extremities are quite common and may occur at the level of the thoracic outlet, axilla, arm, cubital fossa and the hand. In the present study, the anomalous topographic pattern of the subclavian axillary arterial system was revealed in 7.5% of the cadavers, whereas 92.5% exhibited classical pattern of the regional arterial anatomy. The study showed: 1. An aberrant right subclavian artery arising from the arch of aorta, distal to the left subclavian artery. 2. A bilateral common subscapular-circumflex humeral trunk (3.8%) emerging from the 3rd part of the axillary artery (branching into the circumflex humeral and thoracodorsal arteries. 3. A bilateral thoracohumeral trunk arising from the 2nd part of the axillary artery (1.9%) and branching into the lateral thoracic, circumflex humeral, subscapular and thoracodorsal arteries. These anomalies were accompanied by anomalous insertion of flexor digitorum superficialis muscle, a bilateral digastric muscle formed by the abductor pollicis longus and brevis, and an anomalous formation of median nerve by 3 roots. CONCLUSION: The aberrant right subclavian artery associated with right non-recurrent laryngeal nerve and variant branching pattern of the axillary artery are of interest to anatomists, surgeons and radiologists and suggested that these anomalies must be evaluated pre-operatively.

Adult↗

[Seasonal cycles of adipocyte lipogenesis and blood insulin in the young rabbit].

The young domestic rabbit (2.5 months old) shows seasonal variation in metabolism similar to wild mammal. During the annual seasonal cycle we observed variations in the intensity of lipogenesis in isolated perirenal adipocytes; fatty acid synthesis, which uses acetate as a precursor rather than glucose, reaches a maximum in winter and a minimum in spring. The magnitude of the glucose induced pancreatic insulin response varies during the annual seasonal cycle and it follows the variations in the lipogenesis cycle; thus, the plasma IRI increase is highest in winter when maximum lipogenesis occurs.

Acetates↗

Comparative study of erythrocyte glycolytic enzymes in man and in two species of Lagomorphae. (Ochotona rufescens rufescens and Oryctolagus cuniculus).

The authors made a comparative study of red cell enzyme glycolysis in man and in two species of Lagomorphae, the pika and the rabbit. The activities of the 12 enzymes of Embden-Meyerhoff pathway and of the two dehydrogenases of pentose shunt (glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase) were determined. Phosphoglycerate kinase and pyruvate kinase showed quite similar activities in pika erythrocytes and in erythrocytes from human umbilical cord. The levels of these enzymes differed significantly in the pika and in the rabbit. No differences were noted between pyruvate kinases from the rabbit and the neonatal man. The other activities gave values either identical to those found in the adult man or intermediate between the adult and the neonatal man. In the rabbit the levels of glycolitic enzymes were generally lower than in the pika except for lactate dehydrogenase and glycose-6-phosphate dehydrogenase. Some characteristics of erythrocyte metabolism specific to the pika may account for the differences observed in this species. The influence of red cell age cannot explain the variations observed for no significant reticulocytosis was observed in the circulating blood. The percentages found in the pika and the rabbit were essentially identical at determination.

Adult↗

[Autogeny in populations of blood-sucking mosquitoes (Culicidae) on the southern Yamal].

After three-year studies a degree of autogeny in populations of Aedes communis. A. pullatus and A. hexodontus was defined. In various seasons a share of autogenous females in A. communis was stable enough amounting to 30-37%. At the same time considerable variations in the degree of autogeny in some micropopulations of this species were observed. Variations in the ratio between autogenous and non-autogenous individuals reflect a dissimilar effect of varied combinations of ecological factors upon larvae of mosquitoes.

Animals↗

Short term variation of human immunoglobulin levels with an estimation of the day to day physiological variability.

In this work serum Ig levels were determined daily for 14 days in 12 subjects, every two days for 14 days in 19 subjects, every week for 1 month in 11 subjects and fortnightly in 11 subjects for 6 months. The serum IgG, IgM and IgA levels were quantitated by the linear plate method. The day-to-day reproducibility of the technique was checked for a period of one months on seven different samples. The mean coefficient of variation in the reproducibility experiments was found to be 4.8% for IgG, 8.2% for IgM and 5.2% for IgA. Since the observed variation in all groups of subjects was found to be higher than the methodological variation, it appears that physiological variability occurs in the serum Ig levels of an individual. No difference was found between the physiological variances of IgG, IgM and IgA observed in the group with daily analysis and those with determinations every two days. The physiological variations increase when longer periods are considered between consecutive determinations, but the variability of IgG and IgA in the group with fortnightly determinations is less important than that observed in the group with weekly analyses. Some evidence is presented indicating a periodic fluctuation of serum IgG and IgA levels with an amplitude of nearly 20% and with a recurrence rate of two weeks.

Adolescent↗

Review the role of dopamine D4 receptors in schizophrenia and antipsychotic action.

For the past 20 years the most enduring explanation for schizophrenia has been the dopamine hypothesis, which proposes that the dopaminergic system is overactive in this widespread disease. Classically, the D2 receptor formed the core of the dopamine hypothesis since there was considerable evidence for elevations of D2 receptor levels in the brains of schizophrenic patients, and because these receptors served as the primary target in mediating antipsychotic effects of most neuroleptics. However, the dopamine D4 receptor has recently received particular attention in this context. This is because the atypical antipsychotic, clozapine, which is effective in treating refractory schizophrenics without the side-effect profile of typical neuroleptics, displays a 10-fold higher affinity for D4 compared to D2 or D3 receptors. Furthermore, the concentration in plasma water of clinical doses ofclozapine correlates well with its in vitro binding affinity for D4, but not D2 or D3 receptors, suggesting that D4 is a potential target in mediating clozapine's antipsychotic effects. As well, marked elevations in the level of a D4-like site (not identical to the D4 receptor) has been seen in the striatum of postmortem schizophrenic brains, but not in control brains. Finally, the most interesting feature of the D4 receptor is perhaps the array of polymorphisms associated with it, creating structural diversity in this receptor that supercedes all other known catecholamine receptors. The existence of these D4 polymorphisms raises the possibility that structural variations of this receptor may be associated with an increased susceptibility to schizophrenia, or observed variations in individual response to clozapine treatment. However, several studies aimed at investigating these hypotheses could not establish a direct role of D4 in schizophrenia. Furthermore, no association was evident between the polymorphic forms of D4 and susceptibility to schizophrenia, or variable clozapine response. Nevertheless, investigations surrounding this receptor has been far from futile. The observations which support the idea that D4 might serve as a target for clozapine have significantly modified and extended our understanding of mechanisms underlying atypical antipsychotic treatment of schizophrenia, as well as the dopamine hypothesis for schizophrenia. Further characterization of this receptor may prove to be crucial in designing highly effective antipsychotic drugs with minimal contraindications.

Antipsychotic Agents↗

Observations on structure and function of the equine mitral valve.

The anatomy of the equine mitral valve and certain variations observed in 60 adult horses are described. The functional role of this valve, sited between the left atrium and the high pressure-generating left ventricle, is discussed in relation to its anatomical structure. A method of examining the left side of the heart post mortem is described.

Animals↗

Factors contributing to process variance in annual survival of female greater sage-grouse in Montana.

Populations of Greater Sage-Grouse (Centrocercus urophasianus) have declined by 69-99% from historic levels, and information on population dynamics of these birds at a landscape scale is essential to informed management. We examined the relationships between hen survival and a suite of landscape-scale habitat and environmental conditions. We radio-marked 237 female Sage-Grouse and measured 426 vegetation plots during 2001-2004 at four sites in a 3200-km2 landscape in north-central Montana, USA. We used program MARK to model monthly survival rates for 11 seasonal intervals. There was strong support for the best-approximating model (AICc weight = 0.810), which indicated that (1) hen survival varied by season within years and by year within seasons, (2) nesting hens had higher nesting-season survival than non-nesting hens, and (3) individuals at one site had lower hunting-season survival than at other sites. We observed considerable variation in hen survival. Process variation was 0.255, with an expected range of annual survival of 0.12 to 1.0. The ratio of process to total variation was 0.999, indicating that observed variation was real and not attributable to sampling variation. We observed a nearly fourfold difference in maximum and minimum annual survival, ranging from 0.962 +/- 0.024 (mean +/- SE) for nesting hens in 2001-2002 to 0.247 +/- 0.050) for non-nesters in 2003-2004. Low annual survival in 2003 resulted from the compounded effects of a West Nile virus outbreak in August and a severe winter in 2003-2004. Increased hen mortality associated with severe winter weather contrasts with prior beliefs that Sage-Grouse populations are typically unaffected by winter weather conditions and underscores the importance of protecting winter sagebrush (Artemisia spp.) habitats.

Animals↗

Analysis of variations in contrast-detail experiments.

Three sources of variability in a contrast-detail (CD) experiment have been quantitated: within-observer variance, between-observer variance, and sample variance. It is concluded that (1) it is more efficient to increase the numbers of replicated images and observers than to increase the number of readings; (2) sampling and between-observer variations are approximately equal; (3) one can expect approximately 10% standard errors in the measured value of threshold detail or threshold contrast in a CD experiment which employs four observers, four replicate image samples, and one reading per observer.

Models, Structural↗

Heritable variation in the sex pheromone of the almond moth, Cadra cautella.

The sex pheromone of the female almond moth, Cadra cautella, constitutes a highly variable signal. Age and period of the L/D cycle had significant effects on the variation in titers of (Z,E)-9,12-tetradecadienyl acetate (Z9,E12-14:Ac) and (Z)-9-tetradecenyl acetate (Z9-14:Ac) and the ratio of Z9,E12-14:Ac to Z9-14:Ac. Across age classes, minimum and maximum mean titers (ng +/- SE) of Z9,E12-14:Ac and Z9-14:Ac ranged from 8.7 +/- 0.46 to 21 +/- 1.0 and from 2.0 +/- 0.14 to 2.9 +/- 0.15, respectively; the mean ratio of Z9,E12-14:Ac to Z9-14:Ac ranged from 5.2 +/- 0.21 to 11 +/- 0.40. The titers of Z9,E12-14:Ac and Z9-14:Ac and the ratio of Z9,E12-14:Ac to Z9-14:Ac were highest at the onset of the scotophase and lowest at the onset of the photophase. Similarly, the titer of Z9,E12-14:Ac and the ratio of Z9,E12-14:Ac to Z9-14:Ac were highest in females sampled 1 d postemergence and declined over all age classes. The titer of Z9-14:Ac increased from day 1 to day 2, and then declined to levels equivalent to day 1. Analysis of pupal and adult mass demonstrated a positive correlation (r = 0.874, P < 0.001); however, the titer of neither Z9,E12-14:Ac or Z9-14:Ac nor the ratio of Z9,E12-14:Ac to Z9-14:Ac were significantly correlated with pupal mass. Age-related variations in pheromone titer and ratios were heritable. The narrow-sense heritability of the observed variation in 1-d-old females, 1 hr into the scotophase is 1.2 +/- 0.32, 0.75 +/- 0.24, and 0.46 +/- 0.17 for the titer of Z9,E12-14:Ac and Z9-14:Ac and the ratio of Z9,E12-14:Ac to Z9-14:Ac, respectively. A significant additive genetic correlation was observed between that of Z9,E12-14:Ac and Z9-14:Ac, but not between that of either Z9,E12-14:Ac or Z9-14:Ac and the ratio of Z9,E12-14:Ac to Z9-14:Ac. The results of the genetic analyses suggest that the traits of titer of Z9,E12-14:Ac and Z9-14:Ac have a greater potential to respond to selection than the trait of ratio of Z9,E12-14:Ac to Z9-14:Ac.

Aging↗

Variation in physicians' decision-making thresholds in management of a sexually transmitted disease.

OBJECTIVE: To gain insight into the variation in physicians' clinical decisions and further understand the factors that influence physicians' thresholds for testing and treating. DESIGN: Written clinical scenarios were mailed to two groups of physicians who were asked to provide probability estimates of syphilis, how these estimates might change with new information, and when a diagnostic test would be ordered or treatment begun. A model was then used to calculate the probabilities at which physicians ordered tests or initiated treatment. PARTICIPANTS: Group 1 comprised 126 board-certified internists from metropolitan Philadelphia responding from a sample of 360 such physicians randomly selected from a directory. Group 2 consisted of 31 experts in sexually transmitted disease responding from a sample of 50 experts selected by the authors. MEASUREMENTS AND MAIN RESULTS: Experts were willing to obtain a serologic screening test at a lower likelihood of syphilis (0.013%) than were internists (0.034%), and they were willing to obtain a lumbar puncture at a lower likelihood of neurosyphilis (0.165%) than were internists (0.393%). The difference in the groups' thresholds to begin neurosyphilis treatment was not significant. A multivariate model showed that group differences were created by individual characteristics (years in practice, subspecialty board certification, and full-time nonacademic practice) that were associated with higher thresholds for serologic screening. CONCLUSIONS: There are differences in the diagnostic testing practices for syphilis between national experts and internists. Although status in one of these groups alone did not predict the threshold for obtaining syphilis tests, certain individual characteristics were predictive. Examination of physician characteristics helps to explain the variation observed in their practice patterns, and determination of physicians' thresholds aids in analyzing these variations.

Clinical Laboratory Techniques↗

The role of pre-operative templating in primary total knee replacement.

Templating of preoperative X-rays is routinely performed before a total knee replacement. We performed this retrospective study on preoperative templating in primary total knee replacement to assess its accuracy and reproducibility. Preoperative radiographs of 47 patients were templated twice by two observers separately after a gap of 3 months. The size of actual implant used was compared to the size predicted by templating. Data were analysed to assess inter and intra-observer variation. Templating was accurate for both tibial and femoral components in only 53.2% of observations. This study also revealed that templating is a highly-subjective and observer-dependent technique. Inter-observer and intra-observer mismatch was present in 46.8% and 43.6% of readings respectively. We conclude from this study that preoperative templating is neither accurate nor reproducible.

Arthroplasty, Replacement, Knee↗

Characterization of ultra-high molecular weight polyethylene.

The density, ash content and hardness were determined for ultra high molecular weight polyethylene from a single block of medical grade RCH 1000. The effect on these parameters of position within the block and of 2.5 Mrad irradiation was determined. The density was 942 +/- 1 kgm-3. It varied slightly with position and increased slightly after irradiation. The ash content was less than 200 ppm, and varied slightly with position. The ash contained Ca, Al and Si. The hardness (DIN 53456) was 36 MNm-2 and no variation due to position or irradiation could be detected. It was concluded that the observed variations would be unlikely to have a significant effect on the wear behaviour.

Hardness↗

Dental metric comparisons of Morotopithecus and Afropithecus: implications for the validity of the genus Morotopithecus.

Morotopithecus bishopi and Afropithecus turkanensis are two large-bodied hominoid primates from early Miocene deposits of eastern Africa. Researchers have used both cranial and postcranial characters to distinguish these two species. Unfortunately, of the fossil material attributed to each, only the face, palate, and upper dentition are preserved well enough in both species for direct comparisons. There are currently no known directly comparable postcranial elements. In this study, we reevaluated dental characters argued to distinguish the type specimens of Morotopithecus from Afropithecus: relative size of the upper premolars and M3. Exact randomization methods were used to address two questions. First, is it possible to find the degree of dental-size difference observed between Morotopithecus (UMP 62-11) and Afropithecus (KNM-WK 16999) within extant African hominoids? Second, what is the probability of observing the levels of difference found between the fossils among pairs of extant individuals? Metric differences in relative premolar and M3 size were calculated between all possible pairs within the extant sample and the observed difference of the fossil pair was then compared to the resulting distribution of extant pairs. The observed size differences for all comparisons in the fossil teeth were well within the variation observed in the extant African hominoid samples (p>0.05). In light of these results and other currently available cranial evidence, we suggest that the type specimens of Morotopithecus and Afropithecus are not different enough to support taxonomic distinction.

Africa, Eastern↗

Development of the coronary arteries in a murine model of transposition of great arteries.

Transposition of great arteries in humans is associated with a wide spectrum of coronary artery patterns. However, no information is available about how this pattern diversity develops. We have studied the development of the coronary arteries in mouse embryos with a targeted mutation of perlecan, a mutation that leads to ventriculo-arterial discordance and complete transposition in about 70% of the embryos. The perlecan-deficient embryos bearing complete transposition showed a coronary artery pattern consisting of right and left coronary arteries arising from the morphologically dorsal and ventral sinuses of Valsalva, respectively. The left coronary artery gives rise to a large septal artery and runs along the ventral margin of the pulmonary root. In the earliest embryos where transposition could be confirmed (12.5 d post coitum), a dense subepicardial vascular plexus is located in this ventral margin. In wild-type mice, however, capillaries are very scarce on the ventral surface of the pulmonary root and the left coronary artery runs dorsally to this root. We suggest that the establishment of the diverse coronary artery patterns is determined by the anatomical arrangement and the capillary density of the peritruncal vascular plexus, a plexus that spreads from the atrio-ventricular groove and grows around the aortic or pulmonary roots depending on the degree of the short-axis aortopulmonary rotation. This simple model, based on very few assumptions, might explain all the observed variation of the coronary artery patterns in humans with transposition, as well as our observations on the perlecan-deficient and the normal mice.

Animals↗