Implications of an impact origin for the martian hemispheric dichotomy.

The observation that one hemisphere of Mars is lower and has a thinner crust than the other (the 'martian hemispheric dichotomy') has been a puzzle for 30 years. The dichotomy may have arisen as a result of internal mechanisms such as convection. Alternatively, it may have been caused by one or several giant impacts, but quantitative tests of the impact hypothesis have not been published. Here we use a high-resolution, two-dimensional, axially symmetric hydrocode to model vertical impacts over a range of parameters appropriate to early Mars. We propose that the impact model, in addition to excavating a crustal cavity of the correct size, explains two other observations. First, crustal disruption at the impact antipode is probably responsible for the observed antipodal decline in magnetic field strength. Second, the impact-generated melt forming the northern lowlands crust is predicted to derive from a deep, depleted mantle source. This prediction is consistent with characteristics of martian shergottite meteorites and suggests a dichotomy formation time approximately 100 Myr after martian accretion, comparable to that of the Moon-forming impact on Earth.

Towards multimaterial multifunctional fibres that see, hear, sense and communicate.

Virtually all electronic and optoelectronic devices necessitate a challenging assembly of conducting, semiconducting and insulating materials into specific geometries with low-scattering interfaces and microscopic feature dimensions. A variety of wafer-based processing approaches have been developed to address these requirements, which although successful are at the same time inherently restricted by the wafer size, its planar geometry and the complexity associated with sequential high-precision processing steps. In contrast, optical-fibre drawing from a macroscopic preformed rod is simpler and yields extended lengths of uniform fibres. Recently, a new family of fibres composed of conductors, semiconductors and insulators has emerged. These fibres share the basic device attributes of their traditional electronic and optoelectronic counterparts, yet are fabricated using conventional preform-based fibre-processing methods, yielding kilometres of functional fibre devices. Two complementary approaches towards realizing sophisticated functions are explored: on the single-fibre level, the integration of a multiplicity of functional components into one fibre, and on the multiple-fibre level, the assembly of large-scale two- and three-dimensional geometric constructs made of many fibres. When applied together these two approaches pave the way to multifunctional fabric systems.

The prevalence, and predictive value, of abnormal anal cytology to diagnose anal dysplasia in a population of HIV-positive men who have sex with men.

Due to the increasing incidence of anal cancer in HIV-positive men who have sex with men, and the potential to detect and treat high-grade anal dysplasia--the putative anal cancer precursor--we have introduced an anal cytology screening service. Patients with abnormal anal cytology have follow-up high-resolution anoscopy (HRA) with biopsy of lesions clinically suspicious for high-grade dysplasia. In total, 244 men were screened and 235 (96%) of the samples were adequate for cytological interpretation using the Bethesda 2001 system. One hundred and sixty-four (67%) men had abnormal anal cytology, and 93 of them had follow-up HRA and anal biopsy. The positive predictive value for any anal cytological abnormality to predict any degree of anal dysplasia was 95.7+/-2.1%, and for any anal cytological abnormality to predict high-grade anal dysplasia was 55.9+/-5.1%. Abnormal anal cytology was highly predicative of anal dysplasia on biopsy.

Use of the Personality Assessment Inventory to assess psychopathy in offender populations.

The authors investigated the validity of the Antisocial Features (ANT) scale of the Personality Assessment Inventory (PAI; L. C. Morey, 1991) with respect to assessments of psychopathy in 2 offender samples. Study 1 included 46 forensic psychiatric inpatients who were administered the Screening Version of the Hare Psychopathy Checklist (PCL:SV; S. D. Hart, D. N. Cox, & R. D. Hare, 1995). In Study 2, 55 sex offenders were administered the Hare Psychopathy Checklist--Revised (PCL-R; R. D. Hare, 1991). ANT scores correlated highly with the PCL:SV total score (r = .54) and moderately with the PCL-R total score (r = .40). ANT tapped primarily behavioral symptoms of psychopathy rather than interpersonal and affective symptoms. Also, ANT had low to moderate diagnostic efficiency regarding diagnoses of psychopathy, suggesting that it may be better used as a dimensional rather than categorical measure of this construct.

The Spousal Assault Risk Assessment (SARA) Guide: reliability and validity in adult male offenders.

We evaluated the reliability and validity of judgments concerning risk for violence made using the Spousal Assault Risk Assessment Guide (SARA; Kropp, Hart, Webster, & Eaves, 1994, 1995, 1998). We analyzed SARA ratings in six samples of adult male offenders (total N = 2681). The distribution of ratings indicated that offenders were quite heterogeneous with respect to the presence of individual risk factors and to overall perceived risk. Structural analyses of the risk factors indicated moderate levels of internal consistency and item homogeneity. Interrater reliability was high for judgments concerning the presence of individual risk factors and for overall perceived risk. SARA ratings significantly discriminated between offenders with and without a history of spousal violence in one sample, and between recidivistic and nonrecidivistic spousal assaulters in another. Finally, SARA ratings showed good convergent and discriminant validity with respect to other measures related to risk for general and violent criminality.

The impact of Canadian Criminal Code changes on remands and assessments of fitness to stand trial and criminal responsibility in British Columbia.

OBJECTIVE: To evaluate the impact in British Columbia of the 1992 Criminal Code of Canada amendments dealing with remands for fitness to stand trial and not criminally responsible on account of mental disorder (NCRMD) assessments. METHOD: Information on 620 remands for evaluation of fitness to stand trial and/or NCRMD were collected from a sample obtained in British Columbia from 1992 to 1994. The data collected included length of remand order, length of evaluation, criminal charges, psychiatric diagnoses, and the decisions about fitness or NCRMD. RESULTS: Remands increased by about 20% in a 1993-1994 fiscal year compared with the previous year. The majority of evaluations continue to be conducted in an inpatient facility. The goal of a 5-day evaluation period is rarely met: only 12.5% of inpatients were released within 5 days of admission, and the average length of evaluation was about 3 weeks. The use and success of the NCRMD defence appears to be on the rise. In addition, there were some striking differences in remands from metropolitan and nonmetropolitan areas in terms of rates of referral and recommendations of unfitness or NCRMD. CONCLUSION: Results indicated that Bill C-30 has not yet had the anticipated impact on remands as inpatient evaluations continue to be the norm and evaluations typically take several weeks. Suggestions for policy reform and future research are presented.

Client personality disorders affecting wife assault post-treatment recidivism.

Previous evaluations of wife assault treatment outcome have focused generically on whether groups "succeed" or not without a clear criterion of what constituted success. The present study examines the question for whom groups generate the greatest reduction in post-treatment abuse and for whom they work least well. It was found that certain types of personality disordered men had the worst post-treatment prognosis. Specifically, men with high scores on borderline personality, antisocial personality, and avoidant personality fared least well after treatment. However, taken as a generic group, men in treatment had significantly reduced post-treatment abusiveness whether reported by themselves or their wives.

An examination of the relationship of homelessness to mental disorder, criminal behaviour, and health care in a pretrial jail population.

OBJECTIVE: To examine the prevalence of homelessness and its relationship to mental disorder, criminal behaviour, and health care. METHOD: Interview and file data were collected for 790 male admissions to a large, pretrial jail facility over a 12-month period. RESULTS: A significant relationship was found between homelessness and severe mental disorder as well as between homelessness and prior psychiatric history. There were no significant differences found between the homeless and the nonhomeless on the types of crimes for which they were incarcerated or on contact with health care services within the past year. CONCLUSION: The findings indicate the need for a link between the jail and community services for homeless individuals.

Effects of nifedipine on phasic and tonic vasoconstrictor responses to Sgd 101/75 in the isolated perfused rabbit ear artery.

The relative importance of extracellular Ca2+ influx and intracellular Ca2+ release for the vasoconstrictor response to Sgd 101/75 (4(2-imidazoline-amino)-2-methyl-indazol-chlorhydrate), an alpha 1-adrenoceptor agonist, was examined in perfused rabbit ear arteries. Sdg 101/75 induced a phasic and a tonic vasoconstrictor response in a concentration-dependent manner. It is a full agonist on the tonic response but a partial agonist on the phasic response. Nifedipine preferentially inhibited the tonic but not the phasic response to Sgd 101/75. Therefore, Sgd 101/75 appears to require both the intracellular Ca2+ release and extracellular Ca2+ influx for its phasic and tonic responses in rabbit ear arteries, respectively.

The pharmacokinetics and pharmacodynamics of the angiotensin II receptor antagonist losartan potassium (DuP 753/MK 954) in the dog.

The pharmacokinetics and plasma concentration-effect relationship for the nonpeptide angiotensin II (Ang II) receptor antagonist losartan potassium (losartan) have been determined with conscious and anesthetized dogs. The p.o. bioavailability of single doses of 5 to 20 mg/kg was low, 23 to 33%, and independent of the dose. Absorption was rapid, with peak plasma levels observed within 1 hr, and the Cmax and area under the concentration vs. time curve to infinity were proportional to the dose, P < .05. The elimination half-life, 108 to 153 min, was longer than that observed after a single i.v. dose, 41 min, and may reflect both continuous absorption and enterohepatic recirculation because the major route of excretion was via the bile. Single i.v. doses were eliminated rapidly, with a systemic plasma clearance of 22.2 ml/min/kg. When corrected for the blood:plasma distribution ratio, 0.66 to 0.72, the systemic clearance approximates hepatic blood flow, suggesting that clearance is primarily via hepatic metabolism and biliary excretion. Losartan was not distributed extensively to tissues; apparent volume of distribution at steady-state of 0.30 liters/kg and was highly but not extensively bound to plasma proteins; 2.7 to 2.9% unbound (free). The plasma concentration vs. blockade of exogenous Ang II-induced vasopressor response was also determined after a single 3-mg/kg i.v. dose of losartan with a sigmoidal Emax model. Blockade of the pressor response was rapid, 89% at 5 min, and declined to 11% at 240 min postdose. The relationship between concentration and effect was highly significant (r = 0.922, P < .01), with an IC50 (total) of 96 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacology of 2-amino-1,4-dihydro-4-(2-[4-[4-(2-methoxyphenyl)-1- piperazinyl]butylsulfinyl]phenyl)-6-methyl-5-nitro-3-pyridine carboxylic acid methyl ester (XB513), a novel calcium agonist with alpha-1 adrenergic receptor antagonistic.

2-Amino-1,4-dihydro-4-(2-[-4[4-(2-methoxyphenyl)-1-piperazinyl]- butylsulfinyl]phenyl)-6-methyl-5-nitro-3-pyridine carboxylic acid methyl ester (XB513) was designed to combine the calcium agonistic and alpha-1 adrenergic receptor antagonistic properties in the same molecule. It inhibited the specific binding of [3H] nitrendipine in rat cardiac ventricular membranes with an IC50 of 1.2 microM, which is 20-fold greater than the standard calcium agonist Bay K 8644. It displaced [3H]prazosin in rat brain membranes with an IC50 of 29 nM. XB513 caused concentration-dependent positive inotropic responses in isolated electrically paced guinea pig left atria with an EC50 of 1.2 microM and was 10 times less potent than Bay K 8644. In rabbit aorta, XB513 inhibited the contractile effect of 16 nM norepinephrine with an IC50 of 89 nM. In an acute heart failure dog model produced by an overdose of propranolol, XB513 at 0.3 to 3 mg/kg i.v. dose-dependently reversed the decreased mean arterial pressure, cardiac output and dP/dt as well as the increased left ventricular end diastolic pressure induced by propranolol. In conscious instrumented dogs, XB513 at 0.1 and 0.3 mg/kg i.v. increased dP/dt and heart rate significantly, with a minor effect on mean arterial pressure. In summary, this study demonstrates that XB513 is a novel chemical entity possessing both calcium agonistic and alpha-1 adrenergic receptor blocking properties and thus may represent a new class of agents for the treatment of congestive heart failure.

Pharmacology of DuP 532, a selective and noncompetitive AT1 receptor antagonist.

DuP 532 (2-propyl-4-pentafluoroethyl-1-[(2'-(1H-tetrazol-5-yl)bip hen yl- 4-yl)methyl]imidazole-5-carboxylic acid) inhibited the specific binding of [125I]angiotensin II (AII) for the subtype receptor AT1 in rat adrenal cortical membranes with an IC50 of 3.1 X 10(-9) M, but not the [125I]AII binding for the subtype AT2 sites in rat adrenal medulla tissues. It inhibited the contractile response to AII selectively and noncompetitively in the isolated rabbit aorta with a KB value of 1.1 X 10(-10) M. The selective AII antagonism was confirmed in the guinea pig ileum and the pithed rat. In conscious rats, DuP 532 inhibited the AII-induced pressor effect, aldosterone secretion, and water drinking induced by AII. In conscious renal hypertensive rats, DuP 532 decreased blood pressure with i.v. and p.o. ED30 of 0.02 and 0.21 mg/kg, respectively. The antihypertensive effect of DuP 532 at 0.3 to 3 mg/kg p.o. lasted for at least 24 hr. In conscious spontaneously hypertensive rats, DuP 532 given i.v. or p.o. at 0.3 to 3 mg/kg reduced blood pressure dose-dependently. DuP 532, at doses up to 100 mg/kg i.v., did not cause a pressor response in conscious normotensive rats, suggesting lack of agonism. DuP 532 exerted selective AII antagonism in conscious dogs. In conscious furosemide-treated dogs, DuP 532 given either at 0.3 and 1 mg/kg i.v. or at 1 to 10 mg/kg p.o. decreased blood pressure. As the AT1 receptors are responsible for AII-induced vasoconstriction, aldosterone secretion, and water drinking, our study indicates that DuP 532 is a potent, orally active, selective, and noncompetitive AT1 receptor antagonist and antihypertensive agent.

Nonpeptide angiotensin II receptor antagonists. Studies with DuP 753 and EXP3174 in dogs.

DuP 753 (or EXP3174) and PD123177 are nonpeptide angiotensin (AII)-specific ligands, which show high affinities for two AII receptor subtypes, i.e. AT1 and AT2 sites, respectively. In furosemide-treated conscious dogs with high renin, DuP 753 and EXP3714, but not PD123177, were as effective as captopril in lowering blood pressure. Both DuP 753 and EXP3174 exhibited selective vascular antagonism of AII. In conscious dogs with normal renin, DuP 753, but not captopril or EXP3174, caused a dose-dependent but transient decrease in blood pressure. In anesthetized dogs, DuP 753 and captopril caused similar renal vasodilatation and natriuresis. The renal hemodynamic effects of DuP 753 and captopril were more pronounced in dogs with sodium depletion. These results suggest that the AT1 receptor mediates the pressor and renal effects of AII in dogs. The acute transient hypotensive effect of DuP 753 in normal-renin conscious dogs is probably unrelated to AII antagonism.

Psychopathy and the DSM-IV criteria for antisocial personality disorder.

The Axis II Work Group of the Task Force on DSM-IV has expressed concern that antisocial personality disorder (APD) criteria are too long and cumbersome and that they focus on antisocial behaviors rather than personality traits central to traditional conceptions of psychopathy and to international criteria. We describe an alternative to the approach taken in the rev. 3rd ed. of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R; American Psychiatric Association, 1987), namely, the revised Psychopathy Checklist. We also discuss the multisite APD field trials designed to evaluate and compare four criteria sets: the DSM-III-R criteria, a shortened list of these criteria, the criteria for dyssocial personality disorder from the 10th ed. of the International Classification of Diseases (World Health Organization, 1990), and a 10-item criteria set for psychopathic personality disorder derived from the revised Psychopathy Checklist.

Effect of angiotensin II antagonism on canine renal sympathetic nerve function.

The objective of this study was to examine effects of nonpeptide angiotensin II (Ang II) receptor antagonists on renal vasoconstrictor responses to renal nerve stimulation (RNS) and intrarenal injection of norepinephrine in pentobarbital-anesthetized dogs. The subtype 1-selective Ang II receptor antagonists, DuP 753 (2-n-butyl-4-chloro-5-(hydroxymethyl)-1-[(2'-(1H- tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole, potassium salt) and EXP3174 (2-n-butyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl) biphenyl-4-yl)methyl]imidazole-5-carboxylic acid) given intra-arterially to the kidney caused dose-dependent reductions of renal vasoconstrictor responses to RNS but not to norepinephrine. In contrast, the subtype 2-selective Ang II receptor specific ligand, PD 123177 (1-[(4-amino-3-methylphenyl)methyl]-5-(diphenylacetyl)-4,5,6,7- tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid), did not alter the renal vasoconstrictor responses to RNS, norepinephrine, and Ang II in doses of 10-100 micrograms/kg/min i.a. Captopril also reduced the renal vasoconstrictor responses to RNS but not to norepinephrine. However, saralasin did not alter the renal vasoconstrictor responses to RNS and norepinephrine, although it was as effective as DuP 753 and EXP3174 in blocking the renal vasoconstrictor response to Ang II. These results suggest that endogenous Ang II enhances renal adrenergic function at the prejunctional site in anesthetized dogs. Analogous to the Ang II receptor in vascular smooth muscle, the prejunctional Ang II receptor appears to be of subtype 1. Mechanisms accounting for the absence of the inhibition of Ang II-mediated renal adrenergic response by saralasin remain to be determined.

Functional studies of nonpeptide angiotensin II receptor subtype-specific ligands: DuP 753 (AII-1) and PD123177 (AII-2).

DuP 753 and PD123177 are two nonpeptide angiotensin II (AII)-specific ligands, which show high affinities for two respective and distinct subtypes of AII binding sites, i.e., AII-1 and AII-2 sites, respectively, in the rat adrenal gland, brain and uterus. The objective of this study is to identify the functions of these subtype binding sites in the adrenal, sympathetic ganglia, brain and vascular smooth muscle. In conscious rats, DuP 753 at 1, 3 and 10 mg/kg i.v. but not PD123177 at 30 and 100 mg/kg i.v. inhibited the AII-induced aldosterone increase. In the isolated perfused rat adrenal gland, DuP 753 at 10(-6) and 10(-4) M but not PD123177 at 10(-3) M blocked the AII-induced epinephrine secretion. In control and chemically sympathectomized pithed rats, the pressor and tachycardiac responses to AII were blocked by DuP 753 at 10 mg/kg i.v. but not by PD123177 at 100 mg/kg i.v. In conscious rats, DuP 753 at 10 mg/kg s.c. but not PD123177 at 100 mg/kg s.c. inhibited the AII-induced water drinking. In the rabbit aorta, DuP 753 at 10(-6) M but not PD123177 at 10(-4) M inhibited the contractile effect of AII. In conscious renal artery-ligated hypertensive rats, DuP 753 but not PD123177 at 0.1 to 10 mg/kg i.v. lowered blood pressure. In summary, a function of the PD123177-sensitive AII binding site (AII-2) has not yet been identified. However, the DuP 753-sensitive site (AII-1) appears to mediate the AII-induced responses such as adrenal aldosterone and catecholamine secretion, release of catecholamine from sympathetic ganglia, drinking and vasoconstriction.

Performance of criminal psychopaths on selected neuropsychological tests.

Screening batteries of standard neuropsychological tests were administered to 2 different samples (Ns = 90 and 167) of male prison inmates. Scores on the revised Psychopathy Checklist were used to divide inmates in each sample into high, moderate, and low psychopathy groups. There were no group differences in test performance in either of the samples, even when the effects of self-reported psychopathology and substance abuse were taken into account. The overall prevalence of both test-specific and global neuropsychological impairment was low and did not vary significantly across the 3 groups. The results provide no support for traditional brain-damage explanations of psychopathy.