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Morphological allometry is striking due to its evolutionary conservatism, making it an example of a certain sort of evolutionary stasis. Organisms that vary in size, whether for developmental, environmental, or evolutionary reasons, adopt shapes that are predictable from that size alone. There are two major hypotheses to explain this. It may be that natural selection strongly favors each allometric pattern, or that organisms lack the development and genetic capacity to produce variant shapes for selection to act on. Using a high-throughput system for measuring the size and shape of Drosophila wings, we documented an allometric pattern that has been virtually unchanged for 40 million years. We performed an artificial selection experiment on the static allometric slope within one species. In just 26 generations, we were able to increase the slope from 1.1 to 1.4, and decrease it to 0.8. Once artificial selection was suspended, the slope rapidly evolved back to a value near the initial static slope. This result decisively rules out the hypothesis that allometry is preserved due to a lack of genetic variation, and provides evidence that natural selection acts to maintain allometric relationships. On the other hand, it seems implausible that selection on allometry in the wing alone could be sufficiently strong to maintain static allometries over millions of years. This suggests that a potential explanation for stasis is selection on a potentially large number of pleiotropic effects. This seems likely in the case of allometry, as the sizes of all parts of the body may be altered when the allometric slope of one body part is changed. Unfortunately, hypotheses about pleiotropy have been very difficult to test. We lay out an approach to begin the systematic study of pleiotropic effects using genetic manipulations and high-throughput phenotyping., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.)

Nearly every component of hemostasis is altered in sickle cell disease (SCD), yet little evidence exists to guide utilization of venous thromboembolism prophylaxis (VTEP) in this population. This retrospective cohort study included 135 adult patients admitted with a diagnosis of SCD vaso-occlusive crisis to the general medicine service at a tertiary care academic medical center from August 1, 2011 to August 1, 2013. If VTEP was discontinued, the medical record was reviewed for suspicion of VTE, hemorrhage, heparin-induced thrombocytopenia (HIT), or other adverse events. The primary objective was to characterize the safety and effectiveness of VTEP in SCD. The secondary objective was to assess the correlation of VTE with risk factors documented in the general medical population. Most patients (116/135, 85.9%) were prescribed VTEP upon admission, with early discontinuation in 23 patients (19.8%). Reasons for discontinuation included suspicion of VTE (10/116, 8.6%), hemorrhage (5/116, 4.3%), and/or HIT (4/116, 3.4%). Since patients with SCD receiving standard VTEP regimens appear to have similar outcomes compared to medically ill patients in prospective studies, using these regimens appears to be safe when indicated in the opinion of the provider. Once daily injections may be preferred in order to optimize adherence.

Purpose: To determine the cost-effectiveness of fulvestrant 250 mg compared to 500 mg in postmenopausal women with estrogen receptor-positive metastatic breast cancer and disease progression after antiestrogen therapy., Methods: A Markov model was constructed to find the incremental cost-effectiveness of fulvestrant 250 mg monthly when compared with the 500 mg monthly in patients with progression after antiestrogen therapy. The model duration was 24 months. Clinical efficacy data inputs were derived from a phase III clinical trial demonstrating a statistically significant increase in progression-free survival in patients receiving 500 mg versus 250 mg. Cost data utilized were all relevant Ambulatory Payment Classification payment rates from the 2011 Medicare Outpatient Prospective Payment System. A Monte Carlo simulation was performed to test the model at various willingness to pay thresholds., Results: The incremental cost-effectiveness ratio as determined by the Markov model was US$10,972 per month of progression-free survival for the 500 mg dose compared with the 250 mg dose. Using a Monte Carlo simulation, it was found that 500 mg monthly was cost-effective at and above the willingness to pay threshold of US$15,000 per month. A series of one-way sensitivity analyses showed this result is robust to geographical practice variations in costs of drug administration and physician examination., Conclusion: From a third party payer perspective, the value of fulvestrant 500 mg monthly is dependent on the willingness to pay threshold. Despite a labeling change for fulvestrant in September 2010, fulvestrant 250 mg monthly appears to be a viable option in the target population.

A series of meso-substituted metal-free porphyrins has been developed which show high sensitivity to NO2 gas in the sub-5 ppm concentration range. By selecting different substituents, it has been possible to improve in a systematic manner the response time and sensitivity of the porphyrin LB film to NO2. Initially, a sulphonamino substituent yielded a fairly long response time of around 450 s but this was shortened considerably when this substituent was changed for a stearamido group. Further modifications resulted in achieving a porphyrin LB film which exhibited a t50 response time of only 11 s. By using an optically inert calixarene host material in which the porphyrin guest was incorporated, it was possible to obtain t50 values as low as 5 s.

When women smokers become pregnant, they are asked to control weight gain and at the same time to relinquish an addictive drug with weight suppressing effects. For women with serious body image concerns or a history of unhealthful eating patterns, smoking cessation may be particularly problematic. To investigate the relationship of weight concerns with smoking and weight gain during pregnancy and postpartum weight loss strategies, we conducted a retrospective study of women who had given birth to their first child within the past 10 years and were smokers when they became pregnant. We observed that women smokers with high weight and body image concerns (HC) gained significantly more weight during pregnancy-in amounts that far exceeded maximum recommended weight gain-than did women with low concerns (LC). HC were more likely to adopt smoking as a weight-control strategy and to be receptive to multiple weight-control strategies. Although they lost significantly more weight in the first month postpartum than did LC, they had also gained significantly more during pregnancy; the net result was that weight loss as a percentage of weight gained did not differ significantly between groups. HC were significantly less likely to experience food cravings in the first trimester and marginally less likely to vomit than LC. We conclude that early identification of high-risk women, coordination of prenatal care with smoking cessation counseling, and development of effective relapse prevention strategies that specifically address weight issues both during and after pregnancy will be needed if efforts to reduce smoking during pregnancy and postpartum are to be optimized.

Objective: The purpose of this study was to determine the prevalence of interstitial lung disease and the severity of disease in children with systemic sclerosis using high-resolution CT (HRCT)., Subjects and Methods: Eleven children (mean age, 11 years) with scleroderma underwent HRCT, chest radiography, and pulmonary function testing. Eight of these 11 patients also underwent follow-up HRCT. HRCT studies were assessed by two observers for ground-glass attenuation, honeycombing, and other abnormalities. Profusion scores for ground-glass attenuation and honeycombing were determined by multiplying severity of disease by the percentage of lung involvement., Results: Chest radiographs predicted interstitial lung disease in only two patients, whereas HRCT showed interstitial lung disease in eight patients (p = .05). On HRCT, ground-glass attenuation was found in eight patients (73%), honeycombing in five patients (45%), linear opacities in six patients (55%), and subpleural micronodules in seven patients (64%). By the end of the study, 10 patients (91%) had evidence of interstitial lung disease on HRCT. Overall, profusion scores for these 10 patients showed four patients with mild, one with moderate, and five with severe disease. Also, HRCT revealed worsening disease in three of eight patients. We found no correlation between duration of scleroderma and severity of interstitial lung disease (p > .02). Seven patients with evidence of lung disease on HRCT had abnormal results on pulmonary function tests; patients with the highest scores for ground-glass attenuation had the most abnormal results on pulmonary function tests (p < .01)., Conclusion: HRCT shows significant pulmonary disease in children with systemic sclerosis, revealing abnormalities in 91% of our patients. Pulmonary disease should be suspected in children with scleroderma, even if the chest radiograph has normal findings.

Alloantibodies to high-frequency red cell antigens, defined as inherited traits occurring in 92% to 99% or more of the general population, are recognized as a cause of hemolytic transfusion reactions in humans. Here we describe a dog (dog erythrocyte antigen [DEA] 1.2- and DEA 4-positive) sensitized by prior blood transfusion, for which a compatible blood donor could not be found; transfusion of DEA 1.1-negative blood resulted in hemolytic transfusion reactions. Patient serum from days 1 (before first transfusion) and 16 was available for further testing; using 4 dogs with different blood types as potential donors, the major crossmatches were compatible using serum from day 1. However the crossmatches were all incompatible with serum from day 16, indicating that the patient was sensitized to an antigen after the first transfusion. The presence of an alloantibody against DEA 1.1 was not ruled out in this patient, but the incompatibility reactions of patient serum with red cells from donors negative for DEA 1.1 indicated that an alloantibody against a red cell antigen other than DEA 1.1 or any other known DEA for which typing reagents were available (DEA 3, 5, and 7) was present. Subsequently, red cells from 1 of the patient's siblings (DEA 1.2-, 4-, and 7-positive) were found not to agglutinate when incubated with patient's serum from day 16, ruling out the presence of an anti-DEA 7 antibody, and suggesting that an alloantibody against a common red cell antigen missing in the patient and sibling was responsible for the blood incompatibility reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

We developed a staff management system for maintaining treatment gains achieved on a specialized continence unit located in a geriatric nursing home. Geriatric assistants learned to use a prompted voiding procedure to maintain improved dryness for 4 elderly residents. The staff management system included self-monitoring and recording of prompted voiding activities and supervisory monitoring and feedback based on group performance of these activities. Results show that the system was effective in maintaining prompted voiding activities with corresponding maintenance of improved patient continence. However, a gradual decline in staff performance was noted 4 to 5 months after the initiation of the system. During a subsequent phase of the study, provision of individual feedback restored staff performance to previous levels. Results are discussed in relation to the practicality of prompted voiding interventions in nursing home environments and the applicability of staff management systems in this setting.

Indications for the procedure of aponeurotic repair are nearly all of the ptoses that have 8 mm or more of elevation from downward to upward gaze. Such cases have a levator with an adequate striated part, an inadequate superior tarsal (Müller) muscle, and an aponeurosis that has involutional changes such as a dehiscence or disinsertion. Local anesthesia is advised. The incision is made 7 mm above the lash-line, through the skin and pretarsal muscle only. Blunt dissection upward is used until the preaponeurotic fat pad is uncovered. The upper part of the aponeurosis is picked up under the fat pad and sutured to the lower part of the aponeurosis with 5-0 chromic gut. Fifty-seven eyelids in thirty-four patients have been operated on, with excellent results and minimal trauma.

Calcium ions were infused into the external jugular vein of 2 groups of rachitic chicks. One group had been injected with 5 micrograms cholecalciferol (vitamin D3), while the other group remained vitamin D-deficient. After approximately 72 h the chickens were killed and intestinal mucosa homogenates were prepared for the measurement of calcium-binding protein (CaBP). The results indicate that CaBP is not biosynthesised in response to raising the extracellular calcium ion concentration, and only appears if the chickens had received cholecalciferol.

Tryptic, peptic and chymotryptic peptides from the myoglobin of the Cape fox (Vulpes chama) have been aligned with the sequence of the myoglobin of the domestic dog. No amino acid difference was found. Seven carnivore myoglobins now known are compared amongst themselves and it is noted that though the differences between them are found in many different parts of the myoglobin molecule, there seems to be a higher incidence along the loop formed by helix G, the interhelical region GH and the helix H.

Rachitic chicks were injected with different dose-levels of cholecalciferol and several cholecalciferol-related substances, i.e., dihydrotachysterol 3, ergocalciferol, 5,6-transcholecalciferol and 25-hydroxycholecalciferol. The response to treatment was assayed by the amount of cholecalciferol-dependent calcium-binding protein produced in the mucosa of the small intestine. The biological activity of these substances in the healing of rickets in the rat was also estimated except for ergocalciferol. The relative potencies in stimulating calcium-binding protein production were: 25-hydroxycholecalciferol > cholecalciferol > 5,6-trans-cholecalciferol > ergocalciferol > dihydrotachysterol 3.

The level of gluten antibodies has been determined in plasma samples from 36 patients with MS using a haemagglutination technique. Only one of the 36 patients studied showed any evidence of gluten antibodies and the level of antibodies in this patient did not justify putting the patient on a gluten-free diet. This study has provided no evidence to support the use of a gluten-free diet as part of the management of MS.

Whereas the myoglobin of the dolphin surprisingly resembles that of the sperm whale more than that of the porpoise, the myoglobin of a killer whale does not show this feature. It differs from the myoglobins of the dolphin in 6, of the porpoise in 8, and of the sperm whale in 14 positions. The residues in which the cetaceans differ are localised in one particular area of the molecule.

The skeletal myoglobin of the echidna was composed of 153 residues. Its primary amino acid sequence has been determined and compared with that of platypus. Nine differences were found. The number of differences from known marsupial and eutherian myoglobin is about twice as much.