Towards a table-top microscope for nanoscale magnetic imaging using picosecond thermal gradients.

Research advancement in magnetoelectronics is challenged by the lack of a table-top magnetic measurement technique with the simultaneous temporal and spatial resolution necessary for characterizing magnetization dynamics in devices of interest, such as magnetic memory and spin torque oscillators. Although magneto-optical microscopy provides superb temporal resolution, its spatial resolution is fundamentally limited by optical diffraction. To address this challenge, we study heat rather than light as a vehicle to stroboscopically transduce a local magnetic moment into an electrical signal while retaining picosecond temporal resolution. Using this concept, we demonstrate spatiotemporal magnetic microscopy using the time-resolved anomalous Nernst effect (TRANE). Experimentally and with supporting numerical calculations, we find that TRANE microscopy has temporal resolution below 30 ps and spatial resolution determined by the area of thermal excitation. Based on these findings, we suggest a route to exceed the limits imposed by far-field optical diffraction.

Low-velocity granular drag in reduced gravity.

We probe the dependence of the low-velocity drag force in granular materials on the effective gravitational acceleration (g(eff)) through studies of spherical granular materials saturated within fluids of varying density. We vary g(eff) by a factor of 20, and we find that the granular drag is proportional to g(eff), i.e. that the granular drag, F(probe), on a vertical cylinder follows the expected relation F(probe)=ηρ(grain)g(eff)d(probe)h(probe)(2) where the drag is related to the probe's depth of insertion, h(probe); the probe's diameter, d(probe); the grain material's density, ρ(grain); and a dimensionless constant, η. The dimensionless constant shows no systematic variation over four orders of magnitude in effective grain weight, demonstrating that the relation holds over that entire range to within the precision of our data.

Overprescribing of lipid lowering agents.

BACKGROUND: Undertreatment of hyperlipidemia has received considerable attention. However, little is known about trends in overprescribing of lipid lowering agents. We examined these trends and their associations with physician, practice, and organisational factors. METHODS: 2034 physicians were surveyed twice: baseline (1996-7) and follow up (1998-9). On each occasion they were asked: "For what percentage of 50 year old men without other cardiac risk factors would you recommend an oral agent for total cholesterol of 240, LDL 150, and HDL 50 after 6 months on a low cholesterol diet?" During the survey period the National Cholesterol Education Program guidelines did not recommend prescribing for these patients. Binomial and multinomial logistic regressions assessed baseline overprescribing and longitudinal changes in overprescribing, accounting for complex sampling. RESULTS: 39% of physicians recommended prescribing at baseline (round 1), increasing at follow up (round 2) to 51% (p < 0.001). Physicians who were more likely to overprescribe at baseline were less likely to be board certified (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.38 to 0.63; p < 0.001), were in solo or two-physician practices (OR 1.88, 95% CI 1.46 to 2.41; p < 0.001), had more revenue from Medicare (OR 1.10, 95% CI 1.03 to 1.17; p = 0.004) or Medicaid (OR 1.09, 95% CI 1.01 to 1.18; p = 0.03), or were family physicians (OR 1.87, 95% CI 1.35 to 2.58; p < 0.001). Physicians with large increases in overprescibing were more likely than those with small increases in overprescribing to be international medical graduates (OR 2.09, 95% CI 1.20 to 3.64; p = 0.011) and to spend more hours in patient care (OR 1.14, 95% CI 1.03 to 1.26; p = 0.016). CONCLUSIONS: Overprescribing of lipid lowering agents is commonplace and increased. At baseline and longitudinally, overprescribing was primarily associated with physician and practice characteristics and not with organisational factors.

Granulomatous skin lesions in moray eels caused by a novel Mycobacterium species related to Mycobacterium triplex.

An outbreak of granulomatous dermatitis was investigated in a captive population of moray eels. The affected eels had florid skin nodules concentrated around the head and trunk. Histopathological examination revealed extensive granulomatous inflammation within the dermis and subcutaneous fascial plane between the fat and axial musculature. Acid-fast rods were detected within the smallest lesions, which were presumably the ones that had developed earliest. Eventually, after several months of incubation at room temperature, a very slowly growing acid-fast organism was isolated. Sequencing of the 16S rRNA gene identified it as a Mycobacterium species closely related (0.59% divergence) to M. triplex, an SAV mycobacterium. Intradermal inoculation of healthy green moray eels with this organism reliably reproduced the lesion. Experimentally induced granulomatous dermatitis appeared within 2 weeks of inoculation and slowly but progressively expanded during the 2 months of the experiment. Live organisms were recovered from these lesions at all time points, fulfilling Koch's postulates for this bacterium. In a retrospective study of tissues collected between 1993 and 1999 from five spontaneous disease cases, acid-fast rods were consistently found within lesions, and a nested PCR for the rRNA gene also demonstrated the presence of mycobacteria within affected tissues.

16S ribosomal DNA sequence analysis distinguishes biotypes of Streptococcus bovis: Streptococcus bovis Biotype II/2 is a separate genospecies and the predominant clinical isolate in adult males.

We characterized 22 human clinical strains of Streptococcus bovis by genotypic (16S rRNA gene sequence analysis [MicroSeq]; Applied Biosystems, Foster City, Calif.) and phenotypic (API 20 Strep and Rapid ID32 Strep systems (bioMerieux Vitek, Hazelton, Mo.) methods. The strains, isolated from blood, cerebrospinal fluid (CSF), and urine, formed two distinct 16S ribosomal DNA sequence clusters. Three strains which were associated with endocarditis urinary tract infection (UTI), and sepsis clustered with the S. bovis type strain ATCC 33317 (cluster 1); other closely related type strains were S. equinus and S. infantarius. Nineteen strains clustered at a distance of about 2.5% dissimilarity to the S. bovis type strain (cluster 2) and were associated with central nervous system (CNS) disease in addition to endocarditis, UTI, and sepsis. All strains were distinct from S. gallolyticus. Within cluster 2, a single strain grouped with ATCC strain 43143 (cluster 2a) and may be phenotypically distinct. All the other strains formed a second subgroup (cluster 2b) that was biochemically similar to S. bovis biotype II/2 (mannitol negative and beta galactosidase, alpha galactosidase, beta glucuronidase, and trehalose positive). The API 20 Strep system identified isolates of cluster 2b as S. bovis biotype II/2, those of cluster 1 as S. bovis biotype II/1, and that of cluster 2a as S. bovis biotype I. There was an excellent correlation of biotype and genotype: S. bovis biotype II/2 isolates form a separate genospecies distinct from the S. bovis, S. gallolyticus, and S. infantarius type strains and are the most common isolates in adult males.

Elimination of male germ cells in transgenic mice by the diphtheria toxin A chain gene directed by the histone H1t promoter.

Expression of the diphtheria toxin A-chain gene was directed to the male germ line by fusion to 1 kilobase of the 5'-flanking DNA of the rat histone H1t gene. Two independent lines of mice were established that expressed the toxic transgene. Female carriers were fertile; males were sterile although otherwise apparently normal. Adult transgenic males had very small testes that were virtually devoid of germ cells. A developmental study showed that germ cells survived until late fetal life but that testes of 3-day-old transgenic mice were severely depleted of prospermatogonia. During postnatal development of transgenic animals, remaining germ cells progressed to the pachytene stage of meiosis in 10% to 30% of tubular cross sections but degenerated before the completion of meiosis. By 3 mo of age the residual germ cells had almost completely disappeared. These transgenic lines demonstrate the complete tissue specificity of the H1t promoter and reveal a period of its activity just prior to formation of the definitive adult spermatogonial stem cell population. Whereas full expression of H1t occurs only in mid to late pachytene spermatocytes, one or more of the factors that impart tissue specificity to its expression must be transiently activated in the neonatal germ line. This report discusses the possibility that this genetic technique for eliminating germ cells may have practical application in making recipients for spermatogonial stem cell transplantation.

Expression of the rat testis-specific histone H1t gene in transgenic mice. One kilobase of 5'-flanking sequence mediates correct expression of a lacZ fusion gene.

H1t is synthesized in mid to late pachytene spermatocytes of the male germ line and is the only tissue-specific member of the mammalian H1 histone family. As a step toward identifying DNA sequences that confer its tissue-specific expression, we have produced transgenic mice containing the intact rat H1t gene as well as a H1t-lacZ fusion gene. Transgenic mice carrying a 6.8-kilobase fragment of rat genomic DNA encompassing the H1t gene expressed rat H1t at high levels in the testis and in no other organ examined. H1t fragments truncated to within 141 base pairs (bp) of the gene in the 5' direction or within 837 bp in the 3' direction retained testis specificity. Expression of rat H1t protein was also evident in the testes of the transgenic mice, and in some lines the level of rat H1t exceeded that of the mouse protein. The stage of spermatogenesis of transgene expression was assessed by following appearance of transgenic mRNA in developing mice and by immunohistochemistry using an antiserum to rat H1t. In lines from three different constructs, expression was restricted to germinal cells, although in two strongly expressing lines the transgenes were expressed somewhat prematurely in preleptotene spermatocytes. An H1t(-948/+71)-lacZ fusion was also expressed specifically in the spermatocytes and round spermatids of a transgenic line, confirming that sequences sufficient for correct tissue and developmental expression lie within this 1,019-bp segment of the gene.

Violence and schizophrenia: clozapine as a specific antiaggressive agent.

Pharmacological management of persistent aggression in patients with schizophrenia is a difficult clinical dilemma. Clozapine has been shown to be an effective agent in this regard. This study sought to compare the symptomatic response on the Brief Psychiatric Rating Scale (BPRS) between hostile schizophrenic patients and patients without aggression. While dramatic improvements were evident in aggression, both groups were indistinguishable with respect to BPRS response. These results suggest that clozapine may have a selective antiaggressive effect.