The Association between Quality of HIV Care, Loss to Follow-Up and Mortality in Pediatric and Adolescent Patients Receiving Antiretroviral Therapy in Nigeria

Access to pediatric HIV treatment in resource-limited settings has risen significantly. However, little is known about the quality of care that pediatric or adolescent patients receive. The objective of this study is to explore quality of HIV care and treatment in Nigeria and to determine the association between quality of care, loss-to-follow-up and mortality. A retrospective cohort study was conducted including patients ≤18 years of age who initiated ART between November 2002 and December 2011 at 23 sites across 10 states. 1,516 patients were included. A quality score comprised of 6 process indicators was calculated for each patient. More than half of patients (55.5%) were found to have a high quality score, using the median score as the cut-off. Most patients were screened for tuberculosis at entry into care (81.3%), had adherence measurement and counseling at their last visit (88.7% and 89.7% respectively), and were prescribed co-trimoxazole at some point during enrollment in care (98.8%). Thirty-seven percent received a CD4 count in the six months prior to chart review. Mortality within 90 days of ART initiation was 1.9%. A total of 4.2% of patients died during the period of follow-up (mean: 27 months) with 19.0% lost to follow-up. In multivariate regression analyses, weight for age z-score (Adjusted Hazard Ratio (AHR): 0.90; 95% CI: 0.85, 0.95) and high quality indicator score (compared a low score, AHR: 0.43; 95% CI: 0.26, 0.73) had a protective effect on mortality. Patients with a high quality score were less likely to be lost to follow-up (Adjusted Odds Ratio (AOR): 0.42; 95% CI: 0.32, 0.56), compared to those with low score. These findings indicate that providing high quality care to children and adolescents living with HIV is important to improve outcomes, including lowering loss to follow-up and decreasing mortality in this age group

Spectrum of Mutations in the RPGR Gene That Are Identified in 20% of Families with X-Linked Retinitis Pigmentosa

SummaryThe RPGR (retinitis pigmentosa GTPase regulator) gene for RP3, the most frequent genetic subtype of X-linked retinitis pigmentosa (XLRP), has been shown to be mutated in 10%–15% of European XLRP patients. We have examined the RPGR gene for mutations in a cohort of 80 affected males from apparently unrelated XLRP families, by direct sequencing of the PCR-amplified products from the genomic DNA. Fifteen different putative disease-causing mutations were identified in 17 of the 80 families; these include four nonsense mutations, one missense mutation, six microdeletions, and four intronic-sequence substitutions resulting in splice defects. Most of the mutations were detected in the conserved N-terminal region of the RPGR protein, containing tandem repeats homologous to those present in the RCC-1 protein (a guanine nucleotide-exchange factor for Ran-GTPase). Our results indicate that mutations either in as yet uncharacterized sequences of the RPGR gene or in another gene located in its vicinity may be a more frequent cause of XLRP. The reported studies will be beneficial in establishing genotype-phenotype correlations and should lead to further investigations seeking to understand the mechanism of disease pathogenesis

Spectrum of Mutations in the RPGR Gene That Are Identified in 20% of Families with X-Linked Retinitis Pigmentosa

SummaryThe RPGR (retinitis pigmentosa GTPase regulator) gene for RP3, the most frequent genetic subtype of X-linked retinitis pigmentosa (XLRP), has been shown to be mutated in 10%–15% of European XLRP patients. We have examined the RPGR gene for mutations in a cohort of 80 affected males from apparently unrelated XLRP families, by direct sequencing of the PCR-amplified products from the genomic DNA. Fifteen different putative disease-causing mutations were identified in 17 of the 80 families; these include four nonsense mutations, one missense mutation, six microdeletions, and four intronic-sequence substitutions resulting in splice defects. Most of the mutations were detected in the conserved N-terminal region of the RPGR protein, containing tandem repeats homologous to those present in the RCC-1 protein (a guanine nucleotide-exchange factor for Ran-GTPase). Our results indicate that mutations either in as yet uncharacterized sequences of the RPGR gene or in another gene located in its vicinity may be a more frequent cause of XLRP. The reported studies will be beneficial in establishing genotype-phenotype correlations and should lead to further investigations seeking to understand the mechanism of disease pathogenesis

Neonatal outcomes of extremely preterm infants from the NICHD Neonatal Research Network.

OBJECTIVE: This report presents data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network on care of and morbidity and mortality rates for very low birth weight infants, according to gestational age (GA). METHODS: Perinatal/neonatal data were collected for 9575 infants of extremely low GA (22-28 weeks) and very low birth weight (401-1500 g) who were born at network centers between January 1, 2003, and December 31, 2007. RESULTS: Rates of survival to discharge increased with increasing GA (6% at 22 weeks and 92% at 28 weeks); 1060 infants died at CONCLUSION: Although the majority of infants with GAs of \u3eor=24 weeks survive, high rates of morbidity among survivors continue to be observed

Rental Housing Assistance for the 21st Century

Current rental housing assistance programs are not designed to provide a safety net for people whose lives are volatile, or to encourage poor people to live in good locations. These failings can be corrected. HUD should establish a program of rental insurance-like mortgage insurance, but for renters. Low income housing assistance formulas should be revised to reward good neighborhood features, and punish bad

Recursive Cluster Elimination Based Support Vector Machine for Disease State Prediction Using Resting State Functional and Effective Brain Connectivity

Brain state classification has been accomplished using features such as voxel intensities, derived from functional magnetic resonance imaging (fMRI) data, as inputs to efficient classifiers such as support vector machines (SVM) and is based on the spatial localization model of brain function. With the advent of the connectionist model of brain function, features from brain networks may provide increased discriminatory power for brain state classification.In this study, we introduce a novel framework where in both functional connectivity (FC) based on instantaneous temporal correlation and effective connectivity (EC) based on causal influence in brain networks are used as features in an SVM classifier. In order to derive those features, we adopt a novel approach recently introduced by us called correlation-purged Granger causality (CPGC) in order to obtain both FC and EC from fMRI data simultaneously without the instantaneous correlation contaminating Granger causality. In addition, statistical learning is accelerated and performance accuracy is enhanced by combining recursive cluster elimination (RCE) algorithm with the SVM classifier. We demonstrate the efficacy of the CPGC-based RCE-SVM approach using a specific instance of brain state classification exemplified by disease state prediction. Accordingly, we show that this approach is capable of predicting with 90.3% accuracy whether any given human subject was prenatally exposed to cocaine or not, even when no significant behavioral differences were found between exposed and healthy subjects.The framework adopted in this work is quite general in nature with prenatal cocaine exposure being only an illustrative example of the power of this approach. In any brain state classification approach using neuroimaging data, including the directional connectivity information may prove to be a performance enhancer. When brain state classification is used for disease state prediction, our approach may aid the clinicians in performing more accurate diagnosis of diseases in situations where in non-neuroimaging biomarkers may be unable to perform differential diagnosis with certainty

Streptococcus iniae M-Like Protein Contributes to Virulence in Fish and Is a Target for Live Attenuated Vaccine Development

Streptococcus iniae is a significant pathogen in finfish aquaculture, though knowledge of virulence determinants is lacking. Through pyrosequencing of the S. iniae genome we have identified two gene homologues to classical surface-anchored streptococcal virulence factors: M-like protein (simA) and C5a peptidase (scpI).S. iniae possesses a Mga-like locus containing simA and a divergently transcribed putative mga-like regulatory gene, mgx. In contrast to the Mga locus of group A Streptococcus (GAS, S. pyogenes), scpI is located distally in the chromosome. Comparative sequence analysis of the Mgx locus revealed only one significant variant, a strain with an insertion frameshift mutation in simA and a deletion mutation in a region downstream of mgx, generating an ORF which may encode a second putative mga-like gene, mgx2. Allelic exchange mutagenesis of simA and scpI was employed to investigate the potential role of these genes in S. iniae virulence. Our hybrid striped bass (HSB) and zebrafish models of infection revealed that M-like protein contributes significantly to S. iniae pathogenesis whereas C5a peptidase-like protein does not. Further, in vitro cell-based analyses indicate that SiMA, like other M family proteins, contributes to cellular adherence and invasion and provides resistance to phagocytic killing. Attenuation in our virulence models was also observed in the S. iniae isolate possessing a natural simA mutation. Vaccination of HSB with the Delta simA mutant provided 100% protection against subsequent challenge with a lethal dose of wild-type (WT) S. iniae after 1,400 degree days, and shows promise as a target for live attenuated vaccine development.Analysis of M-like protein and C5a peptidase through allelic replacement revealed that M-like protein plays a significant role in S. iniae virulence, and the Mga-like locus, which may regulate expression of this gene, has an unusual arrangement. The M-like protein mutant created in this research holds promise as live-attenuated vaccine

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead