The role of legal coercion in the treatment of offenders with alcohol and heroin problems

This article discusses the ethical justification for and reviews the American evidence on the effectiveness of; treatment for alcohol and heroin dependence that is provided under legal coercion to offenders whose alcohol and drug dependence has contributed to the commission of the offence with which they have been charged or convicted. The article focuses on legally coerced treatment for drink-driving offenders and heroin-dependent property offenders. it outlines the various arguments that have been made for providing such treatment under legal coercion, namely. the over-representation of alcohol and drug dependent persons in prison populations; the contributory causal role of alcohol and other drug problems in the offences that lead to their imprisonment; the high rates of relapse to drug use and criminal involvement after incarceration; the desirability of keeping injecting heroin users out of prisons as a way of reducing the transmission of infectious diseases such as HIV and hepatitis; and the putatively greater cost-effectiveness of treatment compared with incarceration. The ethical objections to legally coerced drug treatment are briefly discussed before the evidence on the effectiveness of legally coerced treatment for alcohol and other drug dependence is reviewed. The evidence, which is primarily from the USA, gives qualified support for some forms of legally coerced drug treatment provided that these programs are well resourced, carefully implemented, and their performance is monitored to ensure that they provide a humane and effective alternative to imprisonment. Expectations about what these programs can achieve also need to be realistic.

Increased number and function of natural killer cells in human immunodeficiency virus 1-positive subjects co-infected with herpes simplex virus 2

P>Natural killer (NK) cells bridge the interface between innate and adaptive immunity and are implicated in the control of herpes simplex virus 2 (HSV-2) infection. In subjects infected with human immunodeficiency virus 1 (HIV-1), the critical impact of the innate immune response on disease progression has recently come into focus. Higher numbers of NK cells are associated with lower HIV-1 plasma viraemia. Individuals with the compound genotype of killer cell immunoglobulin-like receptor (KIR) 3DS1 and human leucocyte antigen (HLA)-Bw4-80I, or who have alleles of KIR3DL1 that encode proteins highly expressed on the NK cell surface, have a significant delay in disease progression. We studied the effect of HSV-2 co-infection in HIV-1-infected subjects, and show that HSV-2 co-infection results in a pan-lymphocytosis, with elevated absolute numbers of CD4+ and CD8+ T cells, and NK cells. The NK cells in HSV-2 co-infected subjects functioned more efficiently, with an increase in degranulation after in vitro stimulation. The number of NK cells expressing the activating receptors NKp30 and NKp46, and expressing KIR3DL1 or KIR3DS1, was inversely correlated with HIV-1 plasma viral load in subjects mono-infected with HIV-1, but not in subjects co-infected with HSV-2. This suggests that HSV-2 infection mediates changes within the NK cell population that may affect immunity in HIV-1 infection.

Lack of effects of clomipramine on Fos and NADPH-diaphorase double-staining in the periaqueductal gray after exposure to an innate fear stimulus

Lack of effects of clomipramine on Fos and NADPH-diaphorase double-staining in the periaqueductal gray after exposure to an innate fear stimulus - nitric oxide (NO) acts as a neurotransmitter in the rat dorsolateral periaqueductal gray (dIPAG), a midbrain structure that modulates fear and defensive behavior. Since defensive reactions can be alleviated by anxiolytic/anti-panic drugs, the present study tested the effect of clomipramine, a serotonin re-uptake inhibitor, on the activation of NO-producing neurons in the dlPAG of rats exposed to a live predator. Double staining was performed using Fos immunohistochemistry and NADPH-diaphorase as techniques to mark neural activation and to detect NO-producing neurons, respectively. Male Wistar rats received acute or chronic (21 days) injections of saline or clomipramine (10 or 20 mg/kg/day) and were exposed to a live cat. The animals exhibited a robust defensive reaction accompanied by an increase in the number of Fos- and doublestained neurons in the dlPAG, suggesting that cat exposure activates NO-producing neurons. Such effects were not significantly attenuated by clomipramine treatments. The intensity of fear reaction correlated with the intensity of neural staining in the dlPAG, regardless the drug treatment. Thus, the present results reinforce the hypothesis that NO may coordinate defensive responses in the dIPAG and indicate that this mechanism may not be modulated by a serotonin re-uptake inhibitor. (C) 2008 Elsevier Inc. All rights reserved.

Role of homocysteic acid in the guinea pig (Cavia porcellus) anterior cingulate cortex in tonic immobility and the influence of NMDA receptors on the dorsal PAG

Tonic immobility (TI) is an innate defensive behaviour elicited by physical restriction and Postural inversion, and is characterised by a profound and temporary state of akinesis. Our previous studies demonstrated that glutamatergic stimulation of the dorsomedial/dorsolateral Portion of periaqueductal gray matter (dPAG) decreases the duration of TI in guinea pigs (Cavia porcellus). Furthermore, evidence suggests that the anterior cingulate cortex (ACC) constitutes an important Source of glutamate for the dPAG. Hence, in the current study, we investigated the effects of microinjection of the excitatory amino acid (EAA) agonist DL-homocysteic acid (DLH) and the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 into the ACC on the duration of TI in guinea pigs. We also assessed the effect of the NMDA receptor antagonist (MK-801) into the dorsal periaqueductal gray matter (dPAG) prior to DLH microinjection into the ACC on the TI duration in the guinea pig. Our results demonstrated that DLH microinjections into the ACC decreased the duration of TI. This effect was blocked by previous MK-801 microinjections into the ACC or into the dPAG. The MK-801 microinjections alone did not influence TI duration. These results provide the new insight that EAAs in the ACC can decrease the duration of TI. The mechanism seems to be dependent on the NMDA receptors present in the ACC and in the dPAG. (C) 2009 Elsevier B.V. All rights reserved.

The presence of CD56/CD16 in T-cell acute lymphoblastic leukaemia correlates with the expression of cytotoxic molecules and is associated with worse response to treatment

Some cases of T-cell acute lymphoblastic leukaemia (ALL) express markers found in natural-killer (NK) cells, such as CD56 and CD16. Out of 84 T-cell ALL cases diagnosed at our Institution, CD56 and/or CD16 was detected in 24 (28.5%), which we designated T/NK-ALL group. Clinical features, laboratory characteristics, survival and expression of cytotoxic molecules were compared in T/NK-ALL and T-ALL patients. Significant differences were observed regarding age (24.9 vs. 16.4 years in T/NK-ALL and T-ALL, respectively, P = 0.006) and platelet counts (177 x 10(9)/l vs. 75 x 10(9)/l in T/NK-ALL and T-ALL, respectively, P = 0.03). Immunophenotypic analysis demonstrated that CD34, CD45RA and CD33 were more expressed in T/NK-ALL patients, whereas CD8 and terminal deoxynucleotidyl transferase were more expressed in T-ALL patients (P < 0.05). The mean overall survival (863 vs. 1869 d, P = 0.02) and disease-free survival (855 vs. 2095 d, P = 0.002) were shorter in patients expressing CD56/CD16. However, multivariate analysis identified CD56/CD16 as an independent prognostic factor only for DFS. Cytotoxic molecules were highly expressed in T/NK-ALL compared to T-ALL. Perforin, granzyme B and TIA-1 were detected in 12/17, 4/17 and 7/24 T/NK-ALL patients and in 1/20, 0/20 and 1/20 T-ALL respectively (P < 0.001, P = 0.036 and P = 0.054). Therefore, the presence of CD56/CD16 was associated with distinct clinical features and expression of cytotoxic molecules in the blasts.

Clinical study of cryosurgery efficacy in the treatment of skin and subcutaneous tumors in dogs and cats

Objective-To evaluate the efficacy of cryosurgery for treatment of skin and subcutaneous tumors in dogs and cats. Study Design-Prospective study. Animals-Dogs (n = 20), cats (10). Methods-Cutaneous or subcutaneous tumors were treated by liquid nitrogen cryosurgical spray (1 cm from target tissue at 90 degrees until a 5-mm halo of frozen tissue was achieved) for 15-60 seconds. Malignant lesions had 3 freeze-thaw cycles benign tumors, 2 cycles. The second or third freeze cycle was performed after complete thaw of the preceding freeze. Wounds healed by second intention. Follow-up was weekly for 1 month and then twice monthly until wounds healed, and final outcome was determined by telephone interview of owners. Results-Tumor size ranged from 0.3 to 11 cm, diameter with 28 (60%) being 0.3-1 cm; 8 (17%) 1.1-3cm, and 11 (23%) >3.4cm. Complications included edema, erythema and for extremity lesions, pain and lameness. Treated lesions (n = 47) had an overall remission of 98% (mean follow-up.. 345 +/- 172.02 days [range, 150-750 days]). One malignant peripheral nerve sheath tumor recurred 7 months after cryosurgical treatment. Conclusion-Cryo surgery is an efficient method for treatment of skin and subcutaneous tumors in dogs and cats. Clinical Relevance-Cryosurgical ablation is an effective means of treating small cutaneous or subcutaneous tumors in dogs and cats, especially in older animals where wound closure or cosmetic outcome might limit surgical excision alone. (C) Copyright 2008 by The American College of Veterinary Surgeons.

Attachment style and coping resources as predictors of coping strategies in the transition to parenthood

The relations among adult attachment style, coping resources, appraised strain, and coping strategies were examined in a prospective study of married couples having their first child (N = 92). Attachment and coping resources were measured during the second trimester of pregnancy, and parenting strain and coping strategies were assessed when the babies were about 6 weeks old. Results supported a theoretical model proposing that attachment is predictive of coping resources and appraised strain, and that attachment, resources, and strain are predictive of coping strategies. Results also highlighted the complexity of associations among attachment, stress, and coping: Gender differences in mean scores and predictive associations were obtained, and some interactions were found between resources and strain in predicting coping strategies. The findings support the utility of integrating theories of attachment and coping in explaining couples' adjustment to important developmental transitions.

Comparative analysis of genetic diversity in the mangrove species Avicennia marina (Forsk.) Vierh. (Avicenniaceae) detected by AFLPs and SSRs

Avicennia marina is an important mangrove species with a wide geographical and climatic distribution which suggests that large amounts of genetic diversity are available for conservation and breeding programs. In this study we compare the informativeness of AFLPs and SSRs for assessing genetic diversity within and among individuals, populations and subspecies of A. marina in Australia. Our comparison utilized three SSR loci and three AFLP primer sets that were known to be polymorphic, and could be run in a single analysis on a capillary electrophoresis system, using different-colored fluorescent dyes. A total of 120 individuals representing six populations and three subspecies were samplcd. At the locus level, SSRs were considerably more variable than AFLPs, with a total of 52 alleles and an average heterozygosity of 0.78. Average heterozygosity for AFLPs was 0.193, but all of the 918 bands scored were polymorphic. Thus, AFLPs were considerably more efficient at revealing polymorphic loci than SSRs despite lower average heterozygosities. SSRs detected more genetic differentiation between populations (19 vs 9%) and subspecies (35 vs 11%) than AFLPs. Principal co-ordinate analysis revealed congruent patterns of genetic relationships at the individual, population and subspecific levels for both data sets. Mantel testing confirmed congruence between AFLP and SSR genetic distances among, but not within, population comparisons, indicating that the markers were segregating inde- pendently but that evolutionary groups (populations and subspecies) were similar. Three genetic criteria of importance for defining priorities for ex situ collections or in situ conservation programs (number of alleles, number of locally common alleles and number of private alleles) were correlated between the AFLP and SSR data sets. The congruence between AFLP and SSR data sets suggest that either method, or a combination, is applicable to expanded genetic studies of mangroves. The codominant nature of SSRs makes them ideal for further population-based investigations, such as mating-system analyses, for which the dominant AFLP markers are less well suited. AFLPs may be particularly useful for monitoring propagation programs and identifying duplicates within collections, since a single PCR assay can reveal many loci at once.

Combining the analyses of introgressive hybridisation and linkage mapping to investigate the genetic architecture of population divergence in the lake whitefish (Coregonus clupeaformis, Mitchill)

Adaptation and reproductive isolation, the engines of biological diversity, are still elusive when discussing the genetic bases of speciation. Namely, the number of genes and magnitude of selection acting positively or negatively on genomic traits implicated in speciation is contentious. Here, we describe the first steps of an ongoing research program aimed at understanding the genetic bases of population divergence and reproductive isolation in the lake whitefish (Coregonus clupeaformis). A preliminary linkage map originating from a hybrid cross between dwarf and normal ecotypes is presented, whereby some of the segregating AFLP markers were found to be conserved among natural populations. Maximum-likelihood was used to estimate hybrid indices from non-diagnostic markers at 998 AFLP loci. This allowed identification of the most likely candidate loci that have been under the influence of selection during the natural hybridisation of whitefish originating from different glacial races. As some of these loci could be identified on the linkage map, the possibility that selection of traits in natural populations may eventually be correlated to specific chromosomal regions was demonstrated. The future prospects and potential of these approaches to elucidate the genetic bases of adaptation and reproductive isolation among sympatric ecotypes of lake whitefish is discussed.

A comparison of peak power in the shoulder press and shoulder throw

The ability to generate peak power is central for performance in many sports. Currently two distinct resistance training methods are used to develop peak power, the heavy weight/slow velocity and light weight/fast velocity regimes. When using the light weight/fast velocity power training method it was proposed that peak power would be greater in a shoulder throw exercise compared with a normal shoulder press. Nine males performed three lifts in the shoulder press and shoulder throw at 30% and 40% of their one repetition maximum (1RM). These lifts were performed identically, except for the release of the bar in the throw condition. A potentiometer attached to the bar measured displacement and duration of the lifts. The time of bar release in the shoulder throw was determined with a pressure switch. ANOVA was used to examine statistically significant differences where the level of acceptance was set at p

Orthographic/phonological facilitation of naming responses in the picture-word task: An event-related fMRI study using overt vocal responding

In the picture-word interference task, naming responses are facilitated when a distractor word is orthographically and phonologically related to the depicted object as compared to an unrelated word. We used event-related functional magnetic resonance imaging (fMRI) to investigate the cerebral hemodynamic responses associated with this priming effect. Serial (or independent-stage) and interactive models of word production that explicitly account for picture-word interference effects assume that the locus of the effect is at the level of retrieving phonological codes, a role attributed recently to the left posterior superior temporal cortex (Wernicke's area). This assumption was tested by randomly presenting participants with trials from orthographically related and unrelated distractor conditions and acquiring image volumes coincident with the estimated peak hemodynamic response for each trial. Overt naming responses occurred in the absence of scanner noise, allowing reaction time data to be recorded. Analysis of this data confirmed the priming effect. Analysis of the fMRI data revealed blood oxygen level-dependent signal decreases in Wernicke's area and the right anterior temporal cortex, whereas signal increases were observed in the anterior cingulate, the right orbitomedial prefrontal, somatosensory, and inferior parietal cortices, and the occipital lobe. The results are interpreted as supporting the locus for the facilitation effect as assumed by both classes of theoretical model of word production. In addition, our results raise the possibilities that, counterintuitively, picture-word interference might be increased by the presentation of orthographically related distractors, due to competition introduced by activation of phonologically related word forms, and that this competition requires inhibitory processes to be resolved. The priming effect is therefore viewed as being sufficient to offset the increased interference. We conclude that information from functional imaging studies might be useful for constraining theoretical models of word production. (C) 2002 Elsevier Science (USA).

Distribution kinetics of solutes in the isolated in-situ perfused rat head using the multiple indicator dilution technique and a physiological two-barrier model

The purpose of this study was to determine the pharmacokinetics of [C-14]diclofenac, [C-14]salicylate and [H-3]clonidine using a single pass rat head perfusion preparation. The head was perfused with 3-[N-morpholino] propane-sulfonic acid-buffered Ringer's solution. Tc-99m-red blood cells and a drug were injected in a bolus into the internal carotid artery and collected from the posterior facial vein over 28 min. A two-barrier stochastic organ model was used to estimate the statistical moments of the solutes. Plasma, interstitial and cellular distribution volumes for the solutes ranged from 1.0 mL (diclofenac) to 1.6 mL (salicylate), 2.0 mL (diclofenac) to 4.2 mL (water) and 3.9 mL (salicylate) to 20.9 mL (diclofenac), respectively. A comparison of these volumes to water indicated some exclusion of the drugs from the interstitial space and salicylate from the cellular space. Permeability-surface area (PS) products calculated from plasma to interstitial fluid permeation clearances (CLPI) (range 0.02-0.40 mL s(-1)) and fractions of solute unbound in the perfusate were in the order: diclofenac>salicylate >clonidine>sucrose (from 41.8 to 0.10 mL s(-1)). The slow efflux of diclofenac, compared with clonidine and salicylate, may be related to its low average unbound fraction in the cells. This work accounts for the tail of disposition curves in describing pharmacokinetics in the head.

Multiple maps and activity-dependent representational plasticity in the anterior Wulst of the adult barn owl (Tyto alba)

In the present study we addressed the issue of somatosensory representation and plasticity in a nonmammalian species, the barn owl. Multiunit mapping techniques were used to examine the representation of the specialized receptor surface of the claw in the anterior Wulst. We found dual somatotopic mirror image representations of the skin surface of the contralateral claw. In addition, we examined both representations 2 weeks after denervation of the distal skin surface of a single digit. In both representations, the denervated digital representation became responsive to stimulation of the adjacent, mutually functional, digit. The mutability and multiple representations indicates that the Wulst provides the owl with sensory processing capabilities analogous to those in mammals.

Gene complementation of airway epithelium in the cystic fibrosis mouse is necessary and sufficient to correct the pathogen clearance and inflammatory abnormalities

Increasingly, cystic fibrosis (CF) is regarded as an inflammatory disorder where the response of the lung to Pseudomonas aeruginosa is exaggerated as a consequence of processes mediated by the product of the CF gene, CFTR. Of importance to any gene-replacement strategy for treatment of CF is the identification of the cell type(s) within the lung milieu that need to be corrected and an indication whether this is sufficient to restore a normal inflammatory response and bacterial clearance. We generated G551D CF mice transgenically expressing the human CFTR gene in two tissue compartments previously demonstrated to mediate a CFTR-dependent inflammatory response: lung epithelium and alveolar macrophages. Following chronic pulmonary infection with P. aeruginosa, CF mice with epithelial-expressed but not macrophage-specific CFTR showed an improvement in pathogen clearance and inflammatory markers compared with control CF animals. Additionally, these data indicate the general role for epithelial cell-mediated events in the response of the lung to bacterial pathogens and the importance of CFTR in mediating these processes.