Genetics and Crime: Integrating New Genomic Discoveries Into Psychological Research About Antisocial Behavior.

Drawing on psychological and sociological theories of crime causation, we tested the hypothesis that genetic risk for low educational attainment (assessed via a genome-wide polygenic score) is associated with criminal offending. We further tested hypotheses of how polygenic risk relates to the development of antisocial behavior from childhood through adulthood. Across the Dunedin and Environmental Risk (E-Risk) birth cohorts of individuals growing up 20 years and 20,000 kilometers apart, education polygenic scores predicted risk of a criminal record with modest effects. Polygenic risk manifested during primary schooling in lower cognitive abilities, lower self-control, academic difficulties, and truancy, and it was associated with a life-course-persistent pattern of antisocial behavior that onsets in childhood and persists into adulthood. Crime is central in the nature-nurture debate, and findings reported here demonstrate how molecular-genetic discoveries can be incorporated into established theories of antisocial behavior. They also suggest that improving school experiences might prevent genetic influences on crime from unfolding.

Antimicrobial activity of extracts from macroalgae Ulva lactuca against clinically important Staphylococci is impacted by lunar phase of macroalgae harvest.

UNLABELLED: Staphylococcus aureus is a common human bacterial pathogen that causes skin and soft tissue infections. Methicillin-resistant Staph. aureus (MRSA) are increasingly drug-resistant, and thus there is great need for new therapeutics to treat Staph. aureus infections. Attention has focused on potential utility of natural products, such as extracts of marine macroalgae, as a source of novel antimicrobial compounds. The green macroalgae Ulva lactuca produces compounds inhibitory to human pathogens, although the effectiveness of U. lactuca extracts against clinically relevant strains of Staph. aureus is poorly understood. In addition, macroalgae produce secondary metabolites that may be influenced by exogenous factors including lunar phase, but whether lunar phase affects U. lactuca antimicrobial capacity is unknown. We sought to evaluate the antibacterial properties of U. lactuca extracts against medically important Staphylococci, and to determine the effect of lunar phase on antimicrobial activity. We report that U. lactuca methanolic extracts inhibit a range of Staphylococci, and that lunar phase of macrolagae harvest significantly impacts antimicrobial activity, suggesting that antimicrobial properties can be maximized by manipulating time of algal harvest. These findings provide useful parameters for future studies aimed at isolating and characterizing U. lactuca anti-Staphylococcal agents. SIGNIFICANCE AND IMPACT OF THE STUDY: The growing prevalence of antibiotic-resistant human pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) has intensified efforts towards discovery and development of novel therapeutics. Marine macroalgae like Ulva lactuca are increasingly recognized as potential sources of antimicrobials, but the efficacy of U. lactuca extracts against common, virulent strains of Staph. aureus is poorly understood. We demonstrate that U. lactuca methanolic extracts inhibit a variety of clinically relevant Staphylococcus strains, and that the antimicrobial activity can be maximized by optimizing time of algal harvest. These findings provide potentially useful parameters for future work of isolating and identifying novel antimicrobial agents from macroalgae.

Phase locking of a 2.7 THz quantum cascade laser to a microwave reference.

We demonstrate the phase locking of a 2.7 THz metal-metal waveguide quantum cascade laser (QCL) to an external microwave signal. The reference is the 15th harmonic, generated by a semiconductor superlattice nonlinear device, of a signal at 182 GHz, which itself is generated by a multiplier chain (x12) from a microwave synthesizer at approximately 15 GHz. Both laser and reference radiations are coupled into a bolometer mixer, resulting in a beat signal, which is fed into a phase-lock loop. The spectral analysis of the beat signal confirms that the QCL is phase locked. This result opens the possibility to extend heterodyne interferometers into the far-infrared range.

Prostate cancer abdominal metastases detected with indium-111 capromab pendetide.

To provide appropriate therapy for prostate cancer, accurate staging of the patient's disease is essential. Determination of tumor size, location, periprostatic extension and metastatic disease in the skeleton and soft tissue are needed to stage properly. Current diagnostic modalities may lead to understaging in 40%-70% of prostate cancer. Detection of metastatic disease, both at the time of initial diagnosis and in patients with suspected local recurrence, can significantly alter the type of therapy given. Clinical studies using the (111)In radiolabeled immunoconjugate, MAb 7E11-C5.3-GYK-DTPA (capromab pendetide), have shown the superiority of radioimmunoscintigraphy over other diagnostic modalities in the detection of both primary and metastatic prostate cancer. Radioimmunoscintigraphy with capromab pendetide depends on expression of tumor-associated antigen rather than lesion size. Earlier detection of extraprostatic invasion and metastases by means of radioimmunoscintigraphy provides valuable information for treatment decisions. A case of metastatic prostate cancer in the abdomen of a patient without local disease, in which the extent of disease was confirmed at autopsy after sudden cardiac arrest, is presented.

Responses of intraocular pressure and the pupil of feline eyes to prostaglandin EP1 and FP receptor agonists.

PURPOSE: Previous studies suggested that FP receptors do not mediate the relaxation of the ciliary muscle and reduction of intraocular pressure in cats by prostaglandin (PG) F2alpha. The present study was undertaken to determine whether the reduction of intraocular pressure in cats induced by PGF2alpha is mediated by FP or other prostaglandin receptors. METHODS: One eye of each cat was treated topically with prostaglandin F2alpha, fluprostenol (FP receptor agonist), or 17-phenyl trinor PGE2 (EP1 receptor agonist) in a dose range of 12.5 to 50 microg. The effects of SC19220 and SC51089 (EP1 receptor antagonists), BWA868c, and SQ29548 (DP and TP receptor antagonists, respectively) on the intraocular response to PGF2alpha were also examined. At intervals up to 6 hours after treatment, intraocular pressure was measured with a pneumotonometer, and pupil diameters were measured with a millimeter ruler. RESULTS: In the dose ranges used, PGF2alpha and 17-phenyl trinor PGE2 decreased intraocular pressure and pupil diameter. The greatest reduction of intraocular pressure by 50.0 microg PGF2alpha was 5.0+/-1.4 mm Hg, whereas that by 50 microg 17-phenyl trinor PGE2 was 6.2+/-1.5 mm Hg. The isopropyl ester of PGF 2alpha at a dose of 1.25 microg reduced intraocular pressure by 3.75+/-0.25 mm Hg at 2 hours. At doses up to 100 microg, fluprostenol did not decrease intraocular pressure but did reduce pupil diameter. SC19220, a weak but selective EP1 receptor antagonist, inhibited the intraocular pressure response to both PGF2alpha and 17-phenyl trinor PGE2. The more potent EP1 receptor antagonist SC51089 had a greater inhibitory effect than SC19220 on the intraocular pressure response to PGF2alpha. Both of these antagonists had a small but non-dose dependent and statistically insignificant effect on the pupil response to PGF2alpha. These observations suggest that in cats, intraocular pressure and pupil responses to PGF2alpha, are mediated by EP1 and FP receptors, respectively. However, SC19220 significantly and dose-dependently inhibited the pupil response to 17-phenyl trinor PGE2alpha suggesting that EP1 receptors mediate pupil response to this agonist. DP and TP receptor antagonists at doses 5- to 20-fold greater than the IC50 values had no effect on the ocular hypotensive response to PGF2alpha. The concurrent administration of 12.5 microg of each of PGF2alpha and 17-phenyl trinor PGE2 did not produce an additive effect on intraocular pressure, indicating that in cats PGF2alpha and 17-phenyl trinor PGE2 act on the same receptor type. CONCLUSIONS: These results suggest that a significant proportion of the ocular hypotensive action of PGF2alpha in cats is mediated by EP1 but not by FP receptor. Evidence was also provided to show that 17-phenyl trinor PGE2 is an ocular hypotensive agent in cats.

Bovine iris-sphincter muscle lacks FP receptor binding sites.

PURPOSE: To determine the affinity, density, and specificity of the binding sites of tritium-labeled prostaglandin F2alpha in membrane preparations of bovine iris-sphincter muscle and corpus luteum. METHODS: Membrane preparations were incubated with 0.312-40.0 nM 3H-prostaglandin F2alpha in saturation experiments, or 8 nM 3H-prostaglandin F2alpha in competition studies, in the presence or absence of varying concentrations of unlabeled prostaglandin F2alpha or other prostaglandin receptor agonists. The affinity (Kd) and the density of the binding sites (Bmax) of 3H-prostaglandin F2alpha in the bovine iris-sphincter muscle were determined by Scatchard analysis. Reverse transcription polymerase chain reaction was performed with bovine iris-sphincter muscle and corpus luteum total RNA and the PCR products were hybridized with specific 32P-labeled probe for further confirmation of FP receptor expression. RESULTS: Specific binding sites of 3H-prostaglandin F2alpha in the membranes of bovine iris-sphincter muscle are saturable with an affinity of 9.5 nM and a density of 596 fmoles/mg of protein. Prostaglandin E2, 17-phenyl trinor prostaglandin E2, and GR63799 (EP, EP1, and EP3 receptor agonists, respectively) inhibited 3H-prostaglandin F2alpha binding with an IC50 of 0.0048 microM, 0.0038 microM, and 0.044 microM, respectively. Fluprostenol, a specific FP receptor agonist did not inhibit 3H-prostaglandin F2alpha binding. In contrast, prostaglandin F2alpha and fluprostenol effectively inhibited 3H-prostaglandin F2alpha binding in the bovine corpus luteum with an IC50 of 0.031 microM and 0.037 microM, respectively. CONCLUSIONS: Our results demonstrate that in the bovine iris-sphincter muscle, FP receptors are not expressed and 3H-prostaglandin F2alpha binds to EP1 and EP3 receptor sites. RT-PCR results demonstrated that FP receptor mRNA, which is present in bovine corpus luteum, is probably absent in iris-sphincter muscle.

An Internet atlas of mouse development.

A prototype two- and three-dimensional color atlas of mouse development is described. The prototype has been developed using two embryos, a 13.5 d normal mouse embryo and a PATCH mutant embryo of the same age. Serial sections of the embryos, with an external registration marker system, introduced into the paraffin embedding process, were prepared by standard histological methods. For the 2D atlas, color images were digitized from 100 consecutive sections of the normal embryo. For the 3D atlas, 300 gray scale images digitized from the mutant embryo were conformally warped and reconstructed into a 3D volume dataset. The external fiducial system facilitated the three-dimensional reconstruction by providing accurate registration of consecutive images and also allowed for precise spatial calibration and the correction for warping artifacts. The atlases, with their associated anatomical knowledge base, will be integrated into a multimedia on-line information resource via the Internet's World Wide Web (WWW) using an enhanced (patent pending, Eòlas Technologies) version of the Mosaic WWW browser program from the National Center for Supercomputer Applications. These programs will provide research biologists with a set of advanced tools to analyze normal and abnormal development.

Technical considerations for acquiring and processing indium-111 capromab pendetide images.

A diagnostic quality 111In capromab pendetide study depends on parameters such as the quality control of the camera, thorough patient preparation, adequate imaging time and accurate computer processing. Comparisons of different patient preparation methods, imaging times, and camera and processing parameters were evaluated to provide high-quality 111In capromab pendetide images and to develop acquisition and processing parameters for 111In capromab pendetide imaging. SPECT images provide the best views of metastatic pelvic nodal involvement. Volume rendered three-dimensional registration best differentiates between normal vasculature and metastatic disease. Optimal acquisition parameters for delayed imaging included 128 x 128 matrix and 65 sec/step. The LFOV dual-head SPECT camera required only one SPECT acquisition that encompassed both the pelvis and abdomen. Planar and SPECT positioning was critical in evaluating questionable lymph nodes. In processing these images, the most diagnostic results were obtained with a three-dimensional low-pass post filter. The most effective patient preparation consisted of an oral cathartic, enema and catheterization when needed.

Lymphoscintigraphy and intraoperative lymphatic mapping of sentinel lymph nodes in melanoma patients.

Identification of sentinel lymph nodes (SLNs) using lymphoscintigraphy, the blue dye technique and intraoperative lymphatic mapping with a gamma-detecting probe has become the standard of care in diagnosing and treating melanoma. Numerous clinical studies have proven the reliability of predicting the histology of remaining lymph nodes in the lymphatic basin from the histologic evaluation of the SLNs. Technical and clinical factors presented in this paper have been shown to increase the accuracy of localization of SLNs. The nuclear medicine technologist shares a vital role in the radiopharmaceutical preparation and administration for preoperative lymphoscintigraphy and intraoperative lymphatic mapping in patients with melanoma.

Antenna model for wire lasers.

An antenna model is proposed for long (L >> A) lasers with subwavelength cross sections (wire lasers). It is shown that the far-field pattern of the wire lasers is determined by the ratio of the wavelength to the length. The radiation of the wire laser is predicted to be concentrated in a narrow beam theta approximately radical(2lambda/L) for laser modes where the longitudinal phase velocity is in synchronism with the velocity of light in air. Experimental results obtained using a terahertz quantum cascade wire laser are in agreement with the model.

Frequency and phase-lock control of a 3 THz quantum cascade laser.

We have locked the frequency of a 3 THz quantum cascade laser (QCL) to that of a far-infrared gas laser with a tunable microwave offset frequency. The locked QCL line shape is essentially Gaussian, with linewidths of 65 and 141 kHz at the -3 and -10 dB levels, respectively. The lock condition can be maintained indefinitely, without requiring temperature or bias current regulation of the QCL other than that provided by the lock error signal. The result demonstrates that a terahertz QCL can be frequency controlled with 1-part-in-10(8) accuracy, which is a factor of 100 better than that needed for a local oscillator in a heterodyne receiver for atmospheric and astronomic spectroscopy.

Studies of reductive elimination reactions to form carbon-oxygen bonds from Pt(IV) complexes.

The platinum(IV) complexes fac-L(2)PtMe(3)(OR) (L(2) = bis(diphenylphosphino)ethane, o-bis(diphenylphosphino)benzene, R = carboxyl, aryl; L = PMe(3), R = aryl) undergo reductive elimination reactions to form carbon-oxygen bonds and/or carbon-carbon bonds. The carbon-oxygen reductive elimination reaction produces either methyl esters or methyl aryl ethers (anisoles) and L(2)PtMe(2), while the carbon-carbon reductive elimination reaction affords ethane and L(2)PtMe(OR). Choice of reaction conditions allows the selection of either type of coupling over the other. A detailed mechanistic study of the reductive elimination reactions supports dissociation of the OR(-) ligand as the initial step for the C-O bond formation reaction. This is followed by a nucleophilic attack of OR(-) upon a methyl group bound to the Pt(IV) cation to produce the products MeOR and L(2)PtMe(2). C-C reductive elimination proceeds from L(2)PtMe(3)(OR) by initial L (L = PMe(3)) or OR(-) (L(2) = dppe, dppbz) dissociation, followed by C-C coupling from the resulting five-coordinate intermediate. Our studies demonstrate that both C-C and C-O reductive elimination reactions from Pt(IV) are more facile in polar solvents, in the presence of Lewis acids, and for OR(-) groups that contain electron withdrawing substituents.

Polar trophoblast (Rauber's layer) of the rabbit blastocyst.

The germinal area of the rabbit blastocyst between 108 h postcoitum (pc) and 168 h pc has been examined by scanning electron and transmission electron microscopy. At 108 h and 120 h pc the polar trophoblast (Rauber's layer) is an intact epithelium overlying the epiblast of the inner cell mass. By 132 h pc the polar trophoblast cells begin to separate at multiple foci, exposing the underlying epiblast. Most of the polar trophoblast cells have become individually separated at 144 h pc. The villous, electron-dense polar trophoblast cells can be easily distinguished from the cells of the epiblast, which have smooth apical surfaces. By 162 h pc the polar trophoblast cells have disappeared from the germinal area. Before the polar trophoblast breaks up, the underlying epiblast cells are only loosely attached to one another. Concurrent with the disintegration of the trophoblast epithelium, the epiblast cells change in shape so that their lateral borders become closely apposed, and junctions develop to form a new epithelium. The epiblast becomes contiguous with the mural trophoblast, and thus the blastocyst does not lose its turgidity as the permeability seal is maintained. There are two classical theories on the fate of the polar trophoblast: the cells die, or they become incorporated into the epiblast as living cells. In newly exposed epiblast the presence of very large phagosomes, which are not found when the polar trophoblast is still intact, favors the first hypothesis and indicates that in the rabbit the epiblast is involved in the phagocytosis of the polar trophoblast.

Differential effects of amphetamine and fenfluramine on appetite for palatable food in humans.

Amphetamine (10 mg), but not fenfluramine (40 mg), suppressed appetite (ie salivation elicited by a palatable food) in ten subjects of normal weight one hour after ingestion. This result supports the hypothesis that the drugs operate through different neural mechanisms. Neither drug affected hunger and food appeal ratings.

Localized expression of the atrial natriuretic factor gene during cardiac embryogenesis.

Expression of the gene encoding atrial natriuretic factor (ANF) during mouse cardiac embryogenesis was studied using in situ hybridization to histologic sections. ANF mRNA was first detected in a subpopulation of myocardial cells at day 8 of embryogenesis. During day 9, abundant hybridization of the ANF probe to the atrium and the primitive ventricle was found. At day 14, strong labeling of cells in both atria and the trabeculated regions of the left ventricle was seen, whereas fewer cells in the right ventricle expressed the ANF gene. The developmental regulation of ANF gene expression in atrial and ventricular cells suggests an important role for this peptide hormone in the embryo. Localized expression of the ANF gene provides a marker for discerning subpopulations of cardiac cells during embryogenesis. Identification of embryonic ventricular ANF mRNA transcripts may have implications with respect to pathologic reexpression of the ANF gene in adult ventricles.

Nursing research priorities of the National Black Nurses Association.

The purpose of this article is to describe the nursing research priorities of the National Black Nurses Association (NBNA). The NBNA is a professional nursing association representing more than 150,000 black nurses throughout the United States and the Eastern Caribbean. This article describes knowledge gaps in nursing research and presents various findings from research studies aimed at defining research priorities in nursing. Recommended research priorities are discussed that are directed toward improving the health of African Americans and other vulnerable populations. The NBNA urges the National Institutes of Health to increase funding to support research initiatives with an emphasis on women's health, particularly the health of women from diverse cultures. Nursing research programs are steadily yielding results, which enable the nursing profession to meet the goal of using the programs include identification of research priorities, acknowledging the vast disparity in nursing research today.

Gentamicin pharmacokinetics in neonates with patent ductus arteriosus.

OBJECTIVES: To determine the effect of patent ductus arteriosus on the pharmacokinetics of gentamicin in neonates and to examine whether any particular pharmacokinetic parameter is of value as a marker of patent ductus arteriosus. DESIGN: Cohort study of neonates treated with gentamicin, according to a standard dosing protocol. SETTING: A 24-bed, Level III, neonatal intensive care unit. PATIENTS: Neonates treated with gentamicin at the time of admission to the neonatal intensive care unit, using a standard protocol, and who were < 36 wks of gestational age. INTERVENTIONS: All patients received a gentamicin loading dose, and had gentamicin concentrations measured at 2 and 12 hrs after this dose, in order to determine pharmacokinetic parameters and calculate the optimum maintenance dose. Those neonates subsequently diagnosed to have patent ductus arteriosus, based on clinical suspicion and echocardiographic confirmation, were compared with those neonates without clinically suspected patent ductus arteriosus. Gentamicin pharmacokinetic parameters were calculated using a one-compartment model. MEASUREMENTS AND MAIN RESULTS: A total of 322 courses of gentamicin were administered (patent ductus arteriosus, n = 106; control, n = 216). Gentamicin clearance was decreased in the patent ductus arteriosus group vs. the control group (40.02 vs. 44.73 mL/kg/hr; p < .0108). Volume of distribution was greater for patent ductus arteriosus patients (0.61 L/kg) than for controls (0.54 L/kg) (p < .0002). Also, volume of distribution was a useful marker for presence of patent ductus arteriosus, with a 92% specificity for patent ductus arteriosus. CONCLUSIONS: Gentamicin dosing should be altered in neonates with patent ductus arteriosus to reflect the impact of higher volume of distribution and lower clearance. When the gentamicin volume of distribution exceeds 0.7 L/kg, it may be of predictive value for the presence of patent ductus arteriosus.

Planning to meet the needs of the hospitalized elderly.

With the elderly population increasing, the number of elderly clients served by almost any type of health care organization will continue to increase. What kind of planning does a hospital nursing administrator need to do to assure that her or his nursing service can give better care to a larger numbers of elderly clients? What are the staffing considerations? Services and facilities considerations? Staff education needs? Budget considerations? Quality-of-care issues? This article will discuss these questions and present Eitel Hospital's comprehensive approach to meeting the needs of the hospitalized elderly.