Origin of Perpendicular Magnetic Anisotropy and Large Orbital Moment in Fe Atoms on MgO.

We report on the magnetic properties of individual Fe atoms deposited on MgO(100) thin films probed by x-ray magnetic circular dichroism and scanning tunneling spectroscopy. We show that the Fe atoms have strong perpendicular magnetic anisotropy with a zero-field splitting of 14.0±0.3 meV/atom. This is a factor of 10 larger than the interface anisotropy of epitaxial Fe layers on MgO and the largest value reported for Fe atoms adsorbed on surfaces. The interplay between the ligand field at the O adsorption sites and spin-orbit coupling is analyzed by density functional theory and multiplet calculations, providing a comprehensive model of the magnetic properties of Fe atoms in a low-symmetry bonding environment.

Rapid isolation of leukocyte subsets from fresh and cryopreserved peripheral blood mononuclear cells in clinical research.

Isolation and processing blood into leukocyte subsets are important processes in research. Although methods have been developed to fractionate small volumes of blood, optimizing the methods and balancing the underlying costs are often necessary. The need for such optimization is particularly critical when processing larger volumes of blood. We describe a simple and reproducible method for processing larger volumes of fresh blood rapidly and consistently, which yields peripheral blood mononuclear cells (PBMCs) and leukocyte subsets with high purity (81-96%; n=13) and higher yields relative to stored blood. RNA isolated from these cells was found to be suitable for downstream applications. Blood stored for 24 hours (n=4) before processing resulted in significantly lower yields of PBMCs (58 percent lower), T cells (52 percent lower), B cells (21 percent lower) and monocytes (25 percent lower) compared to fresh blood. However, the purity of the fractionated cells was comparable to that obtained with fresh blood. Furthermore, we report that the yield and purity of the leukocyte subsets isolated from cryopreserved PBMCs (n=4) were not compromised.

Integration of participatory approaches into surveillance systems.

Animal health surveillance is essential for protecting public health, enhancing access to international markets for animals and their products, and improving animal health, production and welfare. It is of vital importance for protecting and improving the livelihoods of diverse groups of livestock keepers and stakeholders in livestock value chains. Surveillance systems consist of sets of complementary components which generate information to inform risk assessment, decision-making and policy formulation for both national programmes and international trade. Participatory approaches have the potential to add value to surveillance systems by enhancing their performance, especially their sensitivity and timeliness, and encouraging the inclusion of marginalised groups. This paper summarises key considerations in the assessment and design of animal health surveillance and discusses how participatory approaches can be integrated into comprehensive surveillance systems, leading to a more effective overall outcome for both domestic and international purposes.

Dealing with double trouble: Combination deworming against double-drug resistant cyathostomins.

An alternative control regimen for drug-resistant parasites is combination deworming, where two drugs with different modes of action are administered simultaneously to target the same parasite. Few studies have investigated this in equine cyathostomins. We previously reported that an oxibendazole (OBZ) and pyrantel pamoate (PYR) combination was not sustainable against a cyathostomin population with high levels of OBZ and PYR resistance. This study consisted of a field study and two computer simulations to evaluate the efficacy of a moxidectin-oxibendazole (MOX-OBZ) combination against the same cyathostomin population. In the field study, anthelmintic treatments occurred when ten horses exceeded 100 eggs per gram. Fecal egg counts and efficacy evaluations were performed every two weeks. The two simulations utilized weather data as well as equine and parasite population parameters from the field study. The first simulation repeated the treatment schedule used in the field study over a 40 year period. The second evaluated efficacies of combination treatments using selective therapy over 40 years. In the field study, efficacies of MOX and both combination treatments were 100%. The egg reappearance period for MOX was 16 weeks, and the two combination treatments were 12 and 18 weeks. The first (46.7%) and last (40.1%) OBZ efficacies were not significantly different from each other. In the simulation study, the combination treatment delayed MOX resistance development compared to when MOX was used as a single active. This occurred despite the low efficacy of OBZ. The second set of simulations identified combination treatments used with selective therapy to be the most effective at delaying MOX resistance. Overall, this study supports the use of combination treatment against drug-resistant cyathostomins, when one of the actives exhibits high efficacy, and demonstrates benefits of this approach despite substantially lowered efficacy of the other active ingredient.

Planar spin-transfer device with a dynamic polarizer.

In planar nano-magnetic devices magnetization direction is kept close to a given plane by the large easy-plane magnetic anisotropy, for example by the shape anisotropy in a thin film. In this case magnetization shows effectively in-plane dynamics with only one angle required for its description. Moreover, the motion can become overdamped even for small values of Gilbert damping. We derive the equations of effective in-plane dynamics in the presence of spin-transfer torques. The simplifications achieved in the overdamped regime allow to study systems with several dynamic magnetic pieces ("free layers"). A transition from a spin-transfer device with a static polarizer to a device with two equivalent magnets is observed. When the size difference between the magnets is less than critical, the device does not exhibit switching, but goes directly into the "windmill" precession state.

Isolation and characterization of cDNAs encoding PDE5A, a human cGMP-binding, cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase.

Human cGMP-binding, cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase (PDE5A) cDNAs were isolated. A 3.1-kb composite DNA sequence assembled from overlapping cDNAs encodes an 875-amino-acid protein with a predicted molecular mass of 100012 Da (PDE5A1). Extracts prepared from yeast expressing human PDE5A1 hydrolyzed cGMP. This activity was inhibited by the selective PDE5 inhibitors zaprinast and DMPPO. PDE5A mRNA is expressed in aortic smooth muscle cells, heart, placenta, skeletal muscle and pancreas and, to a much lesser extent, in brain, liver and lung. A 5'-splice variant, PDE5A2, encodes an 833-amino-acid protein with eight unique amino acids at the amino terminus. PDE5A maps to chromosome 4q 25-27.

Time trend of female breast carcinoma in situ by race and histology in Connecticut, USA.

A rapid increase of female breast cancer has been reported in many areas of the world and the reasons are not fully understood. While some have attributed the increase to the increasing detection of early stage breast cancer through mammography screening, few studies have directly examined the time trend of in situ breast cancer specifically. This study included all incident cases of female breast carcinoma in situ reported to the Connecticut Tumor Registry between 1973 and 1992. The age-adjusted incidence rates and age-specific incidence rates were calculated by histology and by race. The age-adjusted incidence rates were standardised to the 1970 United States standard million population. The study found that the overall age-adjusted incidence rate of in situ breast cancer has increased dramatically, from 3.53/100000 in 1973-1975 to 17.51/100000 in 1991-1992. The increase was not uniform during the past two decades of cancer registration. In fact, most of the observed rise has occurred since the early 1980s. This increase was found in both Caucasians and Blacks. The results by histology indicate that the dramatic increase in carcinoma in situ is mostly attributable to an increase in ductal carcinoma in situ. The increase was also observed in all age groups 40 years and over. These results are consistent with the use pattern and the reported effect of mammography screening. Therefore, these results are qualitatively consistent with the idea that mammography screening is largely responsible for the recent upsurge in female breast cancer incidence in this population. The study also found that the age group 40-49 years in whites experienced a rapid increase in incidence that began in the same time period as the older age groups, but it has since levelled off. The potential impact of the highly publicized debate regarding the efficacy of mammography in this age group in recent years is discussed.

Distribution of androgen receptor immunoreactivity in the brainstem of male rats.

Gonadal steroids such as testosterone and estrogen are necessary for the normal activation of male rat sexual behavior. The medial preoptic area (MPOA), an important neural substrate regulating mating, accumulates steroids and also expresses functional androgen receptors (AR). The MPOA is intimately connected with other regions implicated in copulation, such as the bed nucleus of the stria terminalis and medial amygdala. Inputs to the MPOA arise from several areas within the brainstem, synapsing preferentially onto steroid sensitive MPOA cells which are activated during sexual activity. Given that little is known about the distribution of AR protein in the brainstem of male rats, we mapped the distribution of AR expressing cells in the pons and medulla using immunocytochemistry. In agreement with previous reports, AR immunoreactivity (AR-ir) was detected in ventral spinal motoneurons and interneurons. In addition, AR-ir was detected in areas corresponding to the solitary tract, lateral paragigantocellular and alpha and ventral divisions of the gigantocellular reticular nuclei, area postrema, raphe pallidus, ambiguus nucleus, and intermediate reticular nucleus. Several regions within the pons contained AR-ir, such as the tegmental and central gray, parabrachial nucleus, locus coeruleus, Barrington's nucleus, periaqueductal gray, and dorsal raphe. In contrast with in situ hybridization studies, auditory and somatosensory areas were AR-ir negative, and, except for very light staining in the prepositus nucleus, areas carrying vestibular information did not display AR-ir. Additionally, cranial nerve motoneurons of the hypoglossal, facial, dorsal vagus, and spinal trigeminal did not display AR-ir in contrast to previous reports. The data presented here indicate that androgens may influence numerous cell groups within the brainstem. Some of these probably constitute a steroid sensitive circuit linking the MPOA to motoneurons in the spinal cord via androgen responsive cells in the caudal ventral medulla.

Hepatobiliary malignancy.

Chronic cholestatic liver disease may be complicated by hepatobiliary malignancy. The early detection of hepatocellular carcinoma and cholangiocarcinoma is of paramount importance in the evaluation of candidates for liver transplantation, which remains the only effective treatment modality for advanced primary biliary cirrhosis and primary sclerosing cholangitis. This article reviews the identification of patients at high risk, current techniques for diagnosis, and makes recommendations for screening high-risk patients. This article also reviews preliminary data from the Mayo Clinic regarding liver transplantation for cholangiocarcinoma following radiation therapy.

Eprosartan, an angiotensin II receptor antagonist, does not affect the pharmacodynamics of glyburide in patients with type II diabetes mellitus.

The potential for eprosartan, a nonbiphenyl tetrazole angiotensin II receptor antagonist, to affect the 24-hour plasma glucose profiles in type II diabetic patients treated with glyburide was investigated in this randomized, placebo-controlled, double-blind (eprosartan-placebo phase only), two-period, period-balanced, crossover study. All patients received a stable oral dose (3.75-10 mg/day) of glyburide for at least 30 days before the first dose of double-blind study medication was administered. Patients were randomized to receive either 200-mg oral doses of eprosartan twice daily or matching oral placebo doses concomitantly with glyburide for 7 days during each treatment period. After a minimum washout period of 14 days, patients were crossed over to the alternate treatment. Serial samples to measure glucose concentrations in plasma were collected over a 24-hour period on the day before administration of eprosartan or placebo and again on day 7. Mean glucose concentrations were comparable between treatment groups before administration of eprosartan or placebo. The point estimate (90% confidence interval) for the ratio of the average mean 24-hour plasma glucose concentrations of eprosartan + glyburide to placebo + glyburide after 7 days of administration was 0.96 (0.90, 1.01). Eprosartan did not significantly alter the 24-hour plasma glucose profile in patients with type II diabetes mellitus who were previously stabilized on glyburide.

Timeliness of automated routine laboratory tests: a College of American Pathologists Q-Probes study of 653 institutions.

Benchmarks for timeliness of early morning routine clinical laboratory tests were developed from over 17,000 urea nitrogen and 16,000 white blood cell count measurements made for inpatients in 653 institutions participating in the College of American Pathologists Q-Probes program. Urea nitrogen and white blood cell counts were considered surrogates for routine chemistry and hematology tests. Laboratories at the 50th percentile reported median urea nitrogen and white blood cell counts by 09.04 and 08.51 h, respectively, whereas those at the 10th percentile reported these median measurements by 11.30 and 11.18 h, respectively. Results were available sooner in non-teaching than teaching institutions, and in smaller rather than larger institutions, with the degree of computerization affecting test availability. Timeliness also was affected by instrument type and mode of operation, but was unaffected by the percentage of stat testing. Based on modeling by regression analysis, there was little evidence that longer routine test turnaround times affect patient length of stay.

Periampullary tumors: which ones should be resected?

Resection was carried out in 118 patients for periampullary lesions. Ninety-eight of these were adenocarcinomas and were treated by the Whipple operation, total pancreatectomy, or local resection (87 patients, 7 patients, and 4 patients, respectively). Diagnosis of pancreatic head carcinoma before resection was falsely positive in 27 percent of the patients. Mortality for radical resection was 4 percent. Five year survival for ampullary carcinoma was 32 percent, and for pancreatic head carcinoma it was 7 percent. Resection of all periampullary tumors is recommended, with the Whipple operation being the standard in most cases.

Testing at the patient's bedside.

Performing laboratory tests at the patient's bedside has become a popular component of care, primarily because of the immediate availability of test results. Bedside glucose monitoring programs have been the prototype for bedside testing and have provided the most experience in this area. Studies of bedside glucose testing have shown that in order to obtain reliably accurate results, there must be a well-designed and well-implemented quality assurance program, which should involve laboratory professionals. However, medical necessity, cost, and alternatives should be thoroughly considered before beginning a bedside testing program, as well as the commitment to a strong quality assurance program.

Unreported dog bites in children.

In 1981, more than 3,200 Pennsylvania children, ages 4 to 18 years, were surveyed about their dog bite histories and attitudes toward animals. Dog bites were much more common than previously reported: 45 percent of children had been bitten during their lifetimes, and 15.5 percent had been bitten in 1980, more than 36 times the rate reported to health authorities. In 1980, the highest bite rate occurred among children 7-12 years old (20 percent). Children were bitten more frequently by the dogs owned by their neighbors, followed by their own dogs, than by strays or by dogs whose owners were not known. Boys were bitten twice as frequently as girls by neighbors' dogs and strays; the bite rates from family dogs were identical in boys and girls. Despite the high bite rates, being bitten was not significantly associated, in most groups of children studied, with a dislike of dogs. These positive attitudes toward dogs may lead to inadequate precautions against bites and to biases in the reporting of bites to health authorities.

Bromine levels in tissue lipids of rats fed brominated fatty acids.

Rats have been fed diets containing either 0.8% brominated corn oil or 0.5% of the ethyl ester of 9,10-dibromostearate or 9,10,12,13-tetrabromostearate. The brominated compounds were incorporated into semisynthetic diets and animals were observed after feeding periods of 5 days to 3 months. With the exception of adipose tissues, the highest concentration of lipid-bound bromine was observed after 5 days on the experimental diets. It was also observed that feeding of the dibromostearate resulted in the highest levels of lipid-bound bromine in heart, whereas the tetrabromostearate tended to result in higher levels of lipid-bound bromine in liver. Brominated corn oil produced more substantial changes than the brominated fatty acid esters, inducing fatty livers and enlarged yellow hearts. Microscopic examination indicated myocardial degeneration and occasional early necrosis.

Toxicology of brominated fatty acids: metabolite concentration and heart and liver changes.

Rats were fed for 35 days diets containing 2% of either brominated corn oil (BCO), monoglyceride of dibromostearate (DBS), monoglyceride of tetrabromostearate (TBS) or a mixture of the two monoglycerides (BMG) which provided proportions of brominated acids comparable to that of the BCO. Hearts from all animals fed BCO were yellow colored and firm in texture. Myocardial cellular degeneration, mild to moderate edema and occasional small necrotic foci were observed. Hearts from animals fed DBS showed moderate edema and some slight necrosis. All diets produced an increase in lipid content of heart. Animals fed the experimental diets developed enlarged livers and showed elevated liver lipid content. The tetrabromostearate appeared to be the more active in producing these changes, in particular a severe intracellular fatty degeneration. Shorter-chain (C-16, C-14) metabolites of di- and tetrabromostearate were identified and the concentration of brominated fatty acids in heart, liver and adipose tissue determined and found to account for 80% of the bromine detected in these tissues by neutron activation analysis. TBS accumulated in liver while the highest concentration of DBS was observed in heart lipids. Although the concentrations of brominated acids in heart and liver lipids were comparable in rats fed BCO or BMG, BCO produced the more pronounced effects. This differential could be due to additional active components in BCO or to a variation in response associated with changes in the location of the fatty acid on the glycerol molecule.

Rescreening in gynecologic cytology. Rescreening of 3762 previous cases for current high-grade squamous intraepithelial lesions and carcinoma--a College of American Pathologists Q-Probes study of 312 institutions.

OBJECTIVE: To quantitate, characterize, and analyze errors identified in the rescreening of previous gynecologic cytology specimens with original diagnoses of "within normal limits" or "benign cellular changes" for current cases diagnosed as carcinoma or high-grade squamous intraepithelial lesion. DESIGN AND SETTING: College of American Pathologists Q-Probes laboratory quality improvement study in 312 laboratories. MAIN OUTCOME MEASURE: False-negative rate in cases rescreened as a result of a current cytologic diagnosis of carcinoma or high-grade squamous intraepithelial lesion. RESULTS: During the examination and reporting of 1,741,515 current Papanicolaou smear cases, participating laboratories rescreened a total of 3762 previous cases that were originally diagnosed, during the 5 years prior to the current case, as being within normal limits or having benign cellular changes. For the rescreened cases, the overall false-negative rates were 10.1% using a narrow definition and 19.7% using a broad definition. The majority of errors for cases originally diagnosed as within normal limits were screening errors, while interpretive errors predominated in those cases originally diagnosed as having benign cellular changes. Eighty-six percent of all false negatives were identified in those previous cases that were originally diagnosed and reported in the 3 years prior to the current case. CONCLUSIONS: Rescreening of previously reported smears, in patients with current abnormal findings, as one component of a complete quality improvement program, identifies errors that may provide information that will enable a laboratory to improve future performance.

Rescreening in gynecologic cytology. Rescreening of 8096 previous cases for current low-grade and indeterminate-grade squamous intraepithelial lesion diagnoses--a College of American Pathologists Q-Probes study of 323 laboratories.

OBJECTIVE: To quantitate, characterize, and analyze errors identified in the rescreening of previous gynecologic cytology specimens with original diagnoses of within normal limits or benign cellular changes for current cases diagnosed as low-grade squamous intraepithelial lesion or squamous intraepithelial lesion of indeterminate grade. DESIGN AND SETTING: College of American Pathologists Q-Probes laboratory quality improvement study in 323 laboratories. MAIN OUTCOME MEASURE: False-negative rate in cases rescreened as a result of a current cytologic diagnosis of low-grade squamous intraepithelial lesion or squamous intraepithelial lesion of indeterminate grade. RESULTS: A total of 8096 smears performed within the 5 years preceding the current examination were rescreened. Of the rescreened cases, 284 (3.5%) were reclassified as a squamous intraepithelial lesion or carcinoma, 474 (5.9%) as atypical squamous cells of uncertain significance, 7 (0.09%) as atypical glandular cells of uncertain significance or glandular intraepithelial lesion, and 39 (0.5%) as unsatisfactory. Ninety-three percent (261/280) of all false-negative cases were identified in cases from the previous 3 years. CONCLUSION: Rescreening archival cytology cases previously diagnosed as within normal limits or benign cellular changes for current cases diagnosed as low-grade squamous intraepithelial lesion or squamous intraepithelial lesion of indeterminate grade will identify screening and diagnostic errors. This may be a useful quality improvement monitor in many laboratories.

Nongynecologic cytology turnaround time: a College of American Pathologists Q-Probes study of 180 laboratories.

OBJECTIVES: To determine the turnaround time for nongynecologic cytology and to identify laboratory and specimen characteristics associated with variations in turnaround time. DESIGN AND SETTING: Prospective evaluation of nongynecologic cytology turnaround times in 180 laboratories. MAIN OUTCOME MEASURE: Nongynecologic cytology case turnaround time. RESULTS: Participants from 180 laboratories submitted turnaround times for 16 950 nongynecologic cytology cases and submitted information describing their laboratories' practice characteristics relating to the processing of nongynecologic cytology specimens. Half of the participating laboratories had mean receipt to report turnaround times of 1.6 calendar days or less and were able to complete 90% of their cases within 3.0 calendar days. Ten percent of participants had mean turnaround times greater than 3.2 days and required 6.0 or more days to report 90% of their cases. Longer turnaround times were associated with processing fluid and fine-needle aspiration specimens, issuing atypical/suspicious for malignancy and nondiagnostic diagnoses, having cytotechnologist students screen slides, having to contact the physician offices for additional information, having to retrieve prior case material for review, and having to perform cell blocks and/or special stains. CONCLUSION: There is an opportunity for laboratories to shorten nongynecologic turnaround time by altering certain laboratory practices.

Follow-up of abnormal gynecologic cytology: a college of American pathologists Q-probes study of 16132 cases from 306 laboratories.

OBJECTIVES: To measure the percentage of women with abnormal gynecologic cytology who have follow-up within 1 year and to identify patient and laboratory characteristics associated with higher percentages of follow-up. DESIGN AND SETTING: Retrospective identification of patients with abnormal cervicovaginal cytology and identification of the initial clinical follow-up activity during the 12 months following the cytologic diagnosis. MAIN OUTCOME MEASURE: Percentage of women receiving follow-up. RESULTS: Three hundred six laboratories reported follow-up information on 16 132 patients with gynecologic cytology diagnoses of carcinoma, high-grade squamous intraepithelial lesion, low-grade squamous intraepithelial lesion, or glandular intraepithelial lesion. The following percentages of women received follow-up within 1 year: 85.6% of patients with cytologic diagnoses of carcinoma, 87.2% with diagnoses of high-grade squamous intraepithelial lesion, 82.7% with diagnoses of low-grade squamous intraepithelial lesion, and 84.9% with diagnoses of glandular intraepithelial lesion. Within 6 months, 82.2% of patients with cytologic diagnoses of carcinoma, 82.4% with diagnoses of high-grade squamous intraepithelial lesion, 71.9% with diagnoses of low-grade squamous intraepithelial lesion, and 74.7% with diagnoses of glandular intra-epithelial lesion received follow-up. Overall, 90. 8% of patients who received follow-up within the 1-year time frame of this study had their follow-up completed within 6 months. Specific follow-up activities and their frequencies are listed for each diagnostic category. Patients 30 years old or younger and pregnant patients had lower follow-up percentages. CONCLUSIONS: With less than 83% of patients with high-grade squamous intraepithelial lesion or carcinoma cytology findings having available documentation of follow-up within 6 months, and less than 88% within 1 year, there is room for improvement in this area of health care. Monitoring and critical analysis of the follow-up process is a starting point for improvement.