Attention deficit/hyperactivity disorder children with a 7-repeat allele of the dopamine receptor D4 gene have extreme behavior but normal performance on critical neuropsychological tests of attention

An association of the dopamine receptor D4 (DRD4) gene located on chromosome 11p15.5 and attention deficit/hyperactivity disorder (ADHD) has been demonstrated and replicated by multiple investigators. A specific allele [the 7-repeat of a 48-bp variable number of tandem repeats (VNTR) in exon 3] has been proposed as an etiological factor in attentional deficits manifested in some children diagnosed with this disorder. In the current study, we evaluated ADHD subgroups defined by the presence or absence of the 7-repeat allele of the DRD4 gene, using neuropsychological tests with reaction time measures designed to probe attentional networks with neuroanatomical foci in D4-rich brain regions. Despite the same severity of symptoms on parent and teacher ratings for the ADHD subgroups, the average reaction times of the 7-present subgroup showed normal speed and variability of response whereas the average reaction times of the 7-absent subgroup showed the expected abnormalities (slow and variable responses). This was opposite the primary prediction of the study. The 7-present subgroup seemed to be free of some of the neuropsychological abnormalities thought to characterize ADHD.

Polymorphic microsatellites in largemouth bronze gudgeon (Coreius guichenoti) developed from repeat-enriched libraries and cross-species amplifications

Largemouth bronze gudgeon (Coreius guichenoti) is a medium-sized fish endemic from the upper Yangtze River of China and its survival is threatened by the construction of the Three Gorges Dam. This study reports 20 new polymorphic microsatellites from a repeat-enriched genomic library with a mean number allele of 5.2, and observed and expected heterozygosities ranging from 0.035 to 1, and from 0.13 to 0.917, respectively. In a cross-species amplification test, nine of the 37 tested loci were found to be also polymorphic in a congeneric species, brass gudgeon (C. heterodon). In addition, other four loci from common carp (Cyprinus carpio) were also polymorphic in C. guichenoti. Out of these 24 polymorphic microsatellites, only three loci significantly deviated from Hardy-Weinberg equilibrium in the sampled population (P < 0.0025), and all pairwise tests for linkage disequilibrium among loci were nonsignificant after applying sequential Bonferroni correction (P > 0.0026). These novel microsatellites provide sufficient levels of polymorphism for studies on population genetics and conservation in C. guichenoti and its related species.

Characterization of two genes encoding leucine-rich repeat-containing proteins in grass carp Ctenopharyngodon idellus

The cDNAs and genes of two different types of leucine- rich repeat-containing proteins from grass carp ( Ctenopharyngodon idellus) were cloned. Homology search revealed that the two genes, designated as GC-GARP and GC-LRG, have 37% and 32% deduced aminoacid sequence similarities with human glycoprotein A repetitions predominant precursor ( GARP) and leucine-rich alpha2-glycoprotein (LRG), respectively. The cDNAs of GC-GARP and GC-LRG encoded 664 and 339 amino acid residues, respectively. GC-GARP and GC-LRG contain many distinct structural and/or functional motifs of the leucine- rich repeat (LRR) subfamily, such as multiple conserved 11-residue segments with the consensus sequence LxxLxLxxN/CxL ( x can be any amino acid). The genes GC-GARP and GC-LRG consist of two exons, with 4,782 bp and 2,119 bp in total length, respectively. The first exon of each gene contains a small 5'-untranslated region and partial open reading frame. The putative promoter region of GC-GARP was found to contain transcription factor binding sites for GATA-1, IRF4, Oct-1, IRF-7, IRF-1, AP1, GATA-box and NFAT, and the promoter region of GC-LRG for MYC-MAX, MEIS1, ISRE, IK3, HOXA9 and C/EBP alpha. Phylogenetic analysis showed that GC-GARP and mammalian GARPs were clustered into one branch, while GC-LRG and mammalian LRGs were in another branch. The GC-GARP gene was only detected in head kidney, and GC-LRG in the liver, spleen and heart in the copepod ( Sinergasilus major)- infected grass carp, indicating the induction of gene expression by the parasite infection. The results obtained in the present study provide insight into the structure of fish LRR genes, and further study should be carried out to understand the importance of LRR proteins in host - pathogen interactions.

Recombinant protein of heptad-repeat HR212, a stable fusion inhibitor with potent anti-HIV action in vitro

HR212, a recombinant protein expressed in Escherichia coli, has been previously reported to inhibit HIV-1 membrane fusion at low nanomolar level. Here we report that HR212 is effective in blocking laboratory strain HIV-1IIIB entry and replication with EC50 values of 3.92±0.62 and 6.59±1.74 nM, respectively, and inhibiting infection by clinic isolate HIV-1KM018 with EC50 values of 44.44±10.20 nM, as well as suppressing HIV-1- induced cytopathic effect with an EC50 value of 3.04±1.20 nM. It also inhibited HIV-2ROD and HIV-2CBL-20 entry and replication in the μM range. Notably, HR212 was highly effective against T20-resistant strains with EC50 values ranging from 5.09 to 7.75 nM. Unlike T20, HR212 showed stability sufficient to inhibit syncytia formation in a time-of-addition assay, and was insensitive to proteinase K digestion. These results suggest that HR212 has great potential to be further developed as novel HIV-1 fusion inhibitor for treatment of HIV/ AIDS patients, particularly for those infected by T20-resistant variants.

Assessment of genetic diversities of selected Laminaria (Laminariales, Phaeophyta) gametophytes by inter-simple sequence repeat analysis

Inter-simple sequence repeat (ISSR) analysis was used to assess genetic diversity among 10 pairs of male and female Laminaria gametophytes. A total of 58 amplification loci was obtained from 10 selected ISSR primers, of which 34 revealed polymorphism among the gametophytes. Genetic distances were calculated with the Dice coefficient ranging from 0.006 to 0.223. A dendrogram based on the unweighted pair-group method arithmetic (UPGMA) average showed that most male and female gametophytes of the same species were clustered together and that 10 pairs of gametophytes were divided into four groups. This was generally consistent with the taxonomic categories. The main group consisted of six pairs of gametophytes, which were selected from Laminaria japonica Aresch. by intensive inbreeding through artificial hybridization. One specific marker was cloned, but was not converted successfully into a sequence characterized amplified region (SCAR) marker. Our results demonstrate the feasibility of applying ISSR markers to evaluate Laminaria germplasm diversities.

Inter-simple sequence repeat (ISSR) analysis of genetic variation of Chondrus crispus populations from North Atlantic

ISSR analysis was used to investigate genetic variations of 184 haploid and diploid samples from nine North Atlantic Chondrus crispus Stackhouse populations and one outgroup Yellow Sea Chondrus ocellatus Holmes population. Twenty-two of 50 primers were selected and 163 loci were scored for genetic diversity analysis. Genetic diversity varied among populations, percentage of polymorphic bands (PPB) ranged from 27.0 to 55.8%, H(Nei's genetic diversity) ranged from 0.11 to 0.20 and I(Shannon's information index) ranged from 0.16 to 0.30. Estimators PPB, H and I had similar values in intra-population genetic diversity, regardless of calculation methods. Analysis of molecular variance (AMOVA) apportioned inter-population and intra-population variations for C crispus, showing more genetic variance (56.5%) occurred in intra-population, and 43.5% variation among nine populations. The Mantel test suggested that genetic differentiation between nine C. crispus populations was closely related with geographic distances (R = 0.78, P = 0.002). Results suggest that, on larger distance scale (ca. > 1000 km), ISSR analysis is useful for determining genetic differentiations of C crispus populations including morphologically inseparable haploid and diploid individuals. (c) 2007 Elsevier B.V. All rights reserved.

Paediatric malaria case-management with artemether-lumefantrine in Zambia: a repeat cross-sectional study

BACKGROUND:Zambia was the first African country to change national antimalarial treatment policy to artemisinin-based combination therapy - artemether-lumefantrine. An evaluation during the early implementation phase revealed low readiness of health facilities and health workers to deliver artemether-lumefantrine, and worryingly suboptimal treatment practices. Improvements in the case-management of uncomplicated malaria two years after the initial evaluation and three years after the change of policy in Zambia are reported.METHODS:Data collected during the health facility surveys undertaken in 2004 and 2006 at all outpatient departments of government and mission facilities in four Zambian districts were analysed. The surveys were cross-sectional, using a range of quality of care assessment methods. The main outcome measures were changes in health facility and health worker readiness to deliver artemether-lumefantrine, and changes in case-management practices for children below five years of age presenting with uncomplicated malaria as defined by national guidelines.RESULTS:In 2004, 94 health facilities, 103 health workers and 944 consultations for children with uncomplicated malaria were evaluated. In 2006, 104 facilities, 135 health workers and 1125 consultations were evaluated using the same criteria of selection. Health facility and health worker readiness improved from 2004 to 2006: availability of artemether-lumefantrine from 51% (48/94) to 60% (62/104), presence of artemether-lumefantrine dosage wall charts from 20% (19/94) to 75% (78/104), possession of guidelines from 58% (60/103) to 92% (124/135), and provision of in-service training from 25% (26/103) to 41% (55/135). The proportions of children with uncomplicated malaria treated with artemether-lumefantrine also increased from 2004 to 2006: from 1% (6/527) to 27% (149/552) in children weighing 5 to 9 kg, and from 11% (42/394) to 42% (231/547) in children weighing 10 kg or more. In both weight groups and both years, 22% (441/2020) of children with uncomplicated malaria were not prescribed any antimalarial drug.CONCLUSION:Although significant improvements in malaria case-management have occurred over two years in Zambia, the quality of treatment provided at the point of care is not yet optimal. Strengthening weak health systems and improving the delivery of effective interventions should remain high priority in all countries implementing new treatment policies for malaria.

Assessing the impulse control of violent offenders using computer-based cognitive performance tasks

The topic of this thesis is impulsivity. The meaning and measurement of impulse control is explored, with a particular focus on forensic settings. Impulsivity is central to many areas of psychology; it is one of the most common diagnostic criteria of mental disorders and is fundamental to the understanding of forensic personalities. Despite this widespread importance there is little agreement as to the definition or structure of impulsivity, and its measurement is fraught with difficulty owing to a reliance on self-report methods. This research aims to address this problem by investigating the viability of using simple computerised cognitive performance tasks as complementary components of a multi-method assessment strategy for impulse control. Ultimately, the usefulness of this measurement strategy for a forensic sample is assessed. Impulsivity is found to be a multifaceted construct comprised of a constellation of distinct sub-dimensions. Computerised cognitive performance tasks are valid and reliable measures that can assess impulsivity at a neuronal level. Self-report and performance task methods assess distinct components of impulse control and, for the optimal assessment of impulse control, a multi-method battery of self-report and performance task measures is advocated. Such a battery is shown to have demonstrated utility in a forensic sample, and recommendations for forensic assessment in the Irish context are discussed.

At what price? A cost-effectiveness analysis comparing trial of labour after previous caesarean versus elective repeat caesarean delivery

Background: Elective repeat caesarean delivery (ERCD) rates have been increasing worldwide, thus prompting obstetric discourse on the risks and benefits for the mother and infant. Yet, these increasing rates also have major economic implications for the health care system. Given the dearth of information on the cost-effectiveness related to mode of delivery, the aim of this paper was to perform an economic evaluation on the costs and short-term maternal health consequences associated with a trial of labour after one previous caesarean delivery compared with ERCD for low risk women in Ireland.Methods: Using a decision analytic model, a cost-effectiveness analysis (CEA) was performed where the measure of health gain was quality-adjusted life years (QALYs) over a six-week time horizon. A review of international literature was conducted to derive representative estimates of adverse maternal health outcomes following a trial of labour after caesarean (TOLAC) and ERCD. Delivery/procedure costs derived from primary data collection and combined both "bottom-up" and "top-down" costing estimations.Results: Maternal morbidities emerged in twice as many cases in the TOLAC group than the ERCD group. However, a TOLAC was found to be the most-effective method of delivery because it was substantially less expensive than ERCD ((sic)1,835.06 versus (sic)4,039.87 per women, respectively), and QALYs were modestly higher (0.84 versus 0.70). Our findings were supported by probabilistic sensitivity analysis.Conclusions: Clinicians need to be well informed of the benefits and risks of TOLAC among low risk women. Ideally, clinician-patient discourse would address differences in length of hospital stay and postpartum recovery time. While it is premature advocate a policy of TOLAC across maternity units, the results of the study prompt further analysis and repeat iterations, encouraging future studies to synthesis previous research and new and relevant evidence under a single comprehensive decision model.

The Use of 'Shame' with Sexual Offenders

This article explores the use of shaming mechanisms with sexual offenders, particularly those who offend against children. Shaming, a central concept in the broader theory of restorative justice, may be of two varieties. The first, ‘disintegrative shaming’, characterises the traditional retributive framework of justice and is evident in recent state led and popular responses to the risk posed by released sexual offenders. Far from ensuring offender integration, the net result is often labelling, stigmatisation, ostracism and a return to offending behaviour. The second, ‘reintegrative shaming’, affirms the offender’s membership within law abiding society. This has been used in several jurisdictions as the basis of restorative support and treatment networks for sexual offenders where the community works in partnership with state and voluntary agencies. Contrary to arguments put forward by critics of restorative justice, this article argues that such cases may be particularly suitable for a restorative approach.