Linkage to HIV care before and after the introduction of provider-initiated testing and counselling in six Rwandan health facilities

HIV testing and counselling forms the gateway to the HIV care and treatment continuum. Therefore, the World Health Organization recommends provider-initiated testing and counselling (PITC) in countries with a generalized HIV epidemic. Few studies have investigated linkage-to-HIV-care among out-patients after PITC. Our objective was to study timely linkage-to-HIV-care in six Rwandan health facilities (HFs) before and after the introduction of PITC in the out-patient departments (OPDs). Information from patients diagnosed with HIV was abstracted from voluntary counselling and testing, OPD and laboratory registers of six Rwandan HFs during three-month periods before (March–May 2009) and after (December 2009–February 2010) the introduction of PITC in the OPDs of these facilities. Information on patients’ subsequent linkage-to-pre-antiretroviral therapy (ART) care and ART was abstracted from ART clinic registers of each HF. To triangulate the findings from HF routine, a survey was held among patients to assess reasons for non-enrolment. Of 635 patients with an HIV diagnosis, 232 (36.5%) enrolled at the ART clinic within 90 days of diagnosis. Enrolment among out-patients decreased after the introduction of PITC (adjusted odds ratio, 2.0; 95% confidence interval, 1.0–4.2; p?=?.051). Survey findings showed that retesting for HIV among patients already diagnosed and enrolled into care was not uncommon. Patients reported non-acceptance of disease status, stigma and problems with healthcare services as main barriers for enrolment. Timely linkage-to-HIV-care was suboptimal in this Rwandan study before and after the introduction of PITC; the introduction of PITC in the OPD may have had a negative impact on linkage-to-HIV-care. Healthier patients tested through PITC might be less ready to engage in HIV care. Fear of HIV stigma and mistrust of test results appear to be at the root of these problems.     

Are executive function and impulsivity antipodes? A conceptual reconstruction with special reference to addiction

Rationale

Although there is considerable interest in how either executive function (EF) or impulsivity relate to addiction, there is little apparent overlap between these research areas.

Objectives

The present paper aims to determine if components of these two constructs are conceptual antipodes??widely separated on a shared continuum.

Methods

EFs and impulsivities were compared and contrasted. Specifically, the definitions of the components of EF and impulsivity, the methods used to measure the various components, the populations of drug users that show deficits in these components, and the neural substrates of these components were compared and contrasted.

Results

Each component of impulsivity had an antipode in EF. EF, however, covered a wider range of phenomena, including compulsivity.

Conclusions

Impulsivity functions as an antipode of certain components of EF. Recognition of the relationship between EF and impulsivity may inform the scientific inquiry of behavioral problems such as addiction. Other theoretical implications are discussed.     

Stem cell policy in the Obama age: UK and US perspectives

In this article, we compare two different approaches to establishing stem cell policy: a defined policy (the UK) and a changing policy (the US). The UK has a clear and precise policy, agreed upon and supported by lawmakers, scientists and the public. By contrast, US federal policy is continuously being updated based on balancing political ideologies and advances in science, and it only regulates federal funding. By investigating these contrasting policy approaches, we hope to demonstrate the impact of policy on stem cell research and public opinion.     

Deletion of human GP1BB and SEPT5 is associated with Bernard-Soulier syndrome, platelet secretion defect, polymicrogyria, and developmental delay

The bleeding disorder Bernard-Soulier syndrome (BSS) is caused by mutations in the genes coding for the platelet glycoprotein GPIb/IX receptor. The septin SEPT5 is important for active membrane movement such as vesicle trafficking and exocytosis in non-dividing cells (i.e. platelets, neurons). We report on a four-year-old boy with a homozygous deletion comprising not only glycoprotein Ibβ (GP1BB) but also the SEPT5 gene, located 5' to GP1BB. He presented with BSS, cortical dysplasia (polymicrogyria), developmental delay, and platelet secretion defect. The homozygous deletion of GP1BB and SEPT5, which had been identified by PCR analyses, was confirmed by Southern analyses and denaturing HPLC (DHPLC). The parents were heterozygous for this deletion. Absence of GPIbβ and SEPT5 proteins in the patient's platelets was illustrated using transmission electron microscopy. Besides decreased GPIb/IX expression, flow cytometry analyses revealed impaired platelet granule secretion. Because the bleeding disorder was extremely severe, the boy received bone marrow transplantation (BMT) from a HLA-identical unrelated donor. After successful engraftment of BMT, he had no more bleeding episodes. Interestingly, also his mental development improved strikingly after BMT. This report describes for the first time a patient with SEPT5 deficiency presenting with cortical dysplasia (polymicrogyria), developmental delay, and platelet secretion defect.     

Sex bias and dosage compensation in the zebra finch versus chicken genomes: General and specialized patterns among birds

We compared global patterns of gene expression between two bird species, the chicken and zebra finch, with regard to sex bias of autosomal versus Z chromosome genes, dosage compensation, and evolution of sex bias. Both species appear to lack a Z chromosome–wide mechanism of dosage compensation, because both have a similar pattern of significantly higher expression of Z genes in males relative to females. Unlike the chicken Z chromosome, which has female-specific expression of the noncoding RNA MHM (male hypermethylated) and acetylation of histone 4 lysine 16 (H4K16) near MHM, the zebra finch Z chromosome appears to lack the MHM sequence and acetylation of H4K16. The zebra finch also does not show the reduced male-to-female (M:F) ratio of gene expression near MHM similar to that found in the chicken. Although the M:F ratios of Z chromosome gene expression are similar across tissues and ages within each species, they differ between the two species. Z genes showing the greatest species difference in M:F ratio were concentrated near the MHM region of the chicken Z chromosome. This study shows that the zebra finch differs from the chicken because it lacks a specialized region of greater dosage compensation along the Z chromosome, and shows other differences in sex bias. These patterns suggest that different avian taxa may have evolved specific compensatory mechanisms.The recent sequencing of the genome of a second bird species, the zebra finch (Taeniopygia guttata) (Warren et al. 2010), now allows important comparative studies to discern patterns of genome organization that are common to birds and distinct from those of other taxa. Here we compare patterns of sex bias and sex chromosome dosage compensation in the zebra finch and chicken (Gallus gallus). The avian chromosomes generally have conserved gene content (Shetty et al. 1999; Nanda et al. 2008), and the zebra finch and chicken have similar numbers of macro- and microchromosomes (Pigozzi and Solari 1998; Itoh and Arnold 2005). The female is heterogametic (ZW) and the male is homogametic (ZZ). The zebra finch and chicken Z chromosomes have similar sets of genes, but have experienced a significant rearrangement of gene order since the two lineages split (Itoh et al. 2006; Warren et al. 2010).Sex chromosome dosage compensation involves diverse sex-specific mechanisms that adjust the expressed dose of genes encoded on heteromorphic sex chromosomes, to offset the sex difference in expression that would otherwise result from the sex difference in copy number of sex chromosome genes (Birchler et al. 2006; Chang et al. 2006; Arnold et al. 2008). Dosage compensation mechanisms operate not only to reduce sex bias in expression of sex chromosome genes, but also to reduce the disparity of expressed dose of sex chromosome and autosomal (A) genes (Nguyen and Disteche 2005). Three different X chromosome-wide mechanisms of dosage compensation are reported for Caenorhabditis elegans, Drosophila melanogaster, and mammals, but all of these mechanisms are effective in reducing the expected sexual disparity of X gene expression. Birds show no chromosome-wide dosage compensation mechanism, based on small-scale and genome-wide analyses (Baverstock et al. 1982; Kuroda et al. 2001; McQueen et al. 2001; Kuroiwa et al. 2002; Ellegren et al. 2007; Itoh et al. 2007). In chickens, expression of Z gene mRNAs are, on average, about 1.4–1.6 times higher in males than females, even before gonadal differentiation, a remarkable sex difference for an entire sex chromosome (Arnold et al. 2008; Zhang et al. 2010). The lack of effective dosage compensation is reported also for the silkworm moth, another ZW system (Zha et al. 2009), suggesting an unexpected difference in selection pressures on XX/XY versus ZZ/ZW systems (Mank 2009).Although most chicken Z genes are expressed at higher levels in males than females, some genes show no sex bias, indicating that some mechanism compensates for the sexual disparity in gene copy number. Some compensated genes are concentrated in a region of the short arm of the chicken Z chromosome, near the MHM (male hypermethylated) locus (Melamed and Arnold 2007; Arnold et al. 2008; Mank and Ellegren 2009a,b; Melamed et al. 2009). The MHM locus encodes a non-coding RNA MHM that is expressed only in females, possibly because of the greater methylation of DNA near MHM in males (Teranishi et al. 2001). Moreover, the chromatin near MHM shows female-specific acetylation of histone 4 at lysine 16, a modification that is predicted to increase gene expression (Bisoni et al. 2005). These findings suggest that the ncRNA MHM may participate in a local dosage-compensation mechanism that increases expression of near-MHM genes in females. Here we present evidence that the putative MHM mechanism is not common to all birds, and present other evidence that regulation of sex bias in gene expression differs in zebra finch and chicken despite their common pattern of ineffective compensation of Z chromosome gene expression.     

Comparison of the effects of genetic and environmental risk factors on in situ and invasive ductal breast cancer

Little is known about the etiology of in situ ductal breast cancer (DCIS) or what influences its possible progression to invasive ductal disease. Comparison of risk factors for DCIS and invasive ductal cancer may throw some light on these issues. We estimated relative risks for DCIS and invasive ductal breast cancer according to 12 genetic and eight environmental risk factors among 1.1 million postmenopausal women in a large prospective UK study. There was no strong evidence of a different association with DCIS versus invasive ductal cancer for any of the 12 susceptibility loci examined. We also found similar associations of age at menarche, age at first birth, parity, age at menopause, family history of breast cancer and use of hormone replacement therapy with DCIS and invasive ductal cancer. Only body mass index (BMI) showed a clear difference in association in that it was positively associated with the risk of invasive ductal cancer but not DCIS (RRs per 5 kg/m(2) = 1.20 and 1.01, respectively; p-value for heterogeneity = 0.002). The very similar risk factor profiles observed here for DCIS and invasive ductal cancer suggest that DCIS is a precursor of invasive ductal cancer and most risk factors affect the risk of invasive ductal cancer primarily through their effects on the risk of DCIS. The lack of association between BMI and DCIS suggests a greater influence of BMI on disease progression.     

Design and Cohort Characteristics of the Social Spectrum Study: A Multicenter Study of the Autism Spectrum Among Clinically Referred Children

This paper provides an overview of the design and cohort characteristics of the Social Spectrum Study: a clinical cohort study that used a two-phase sampling design to identify children at risk for ASD. After screening 1281 children aged 2.5–10 years who had been consecutively referred to one of six mental health services in the Netherlands, children who screened positive for ASD (n?=?428) and a random selection of screen negatives (n?=?240) were invited to participate in diagnostic assessments and questionnaires regarding the child, family and society. A 1-year follow-up was also conducted. Results from this study may contribute to knowledge of the identification and characterization of children with ASD, family processes, and the impact of ASD on the family and society.