Loss to programme between HIV diagnosis and initiation of antiretroviral therapy in sub-Saharan Africa: systematic review and meta-analysis

Objectives  To assess the proportion of patients lost to programme (died, lost to follow-up, transferred out) between HIV diagnosis and start of antiretroviral therapy (ART) in sub-Saharan Africa, and determine factors associated with loss to programme. Methods  Systematic review and meta-analysis. We searched PubMed and EMBASE databases for studies in adults. Outcomes were the percentage of patients dying before starting ART, the percentage lost to follow-up, the percentage with a CD4 cell count, the distribution of first CD4 counts and the percentage of eligible patients starting ART. Data were combined using random-effects meta-analysis. Results  Twenty-nine studies from sub-Saharan Africa including 148 912 patients were analysed. Six studies covered the whole period from HIV diagnosis to ART start. Meta-analysis of these studies showed that of the 100 patients with a positive HIV test, 72 (95% CI 60-84) had a CD4 cell count measured, 40 (95% CI 26-55) were eligible for ART and 25 (95% CI 13-37) started ART. There was substantial heterogeneity between studies (P < 0.0001). Median CD4 cell count at presentation ranged from 154 to 274 cells/μl. Patients eligible for ART were less likely to become lost to programme (25%vs. 54%, P < 0.0001), but eligible patients were more likely to die (11%vs. 5%, P < 0.0001) than ineligible patients. Loss to programme was higher in men, in patients with low CD4 cell counts and low socio-economic status and in recent time periods. Conclusions  Monitoring and care in the pre-ART time period need improvement, with greater emphasis on patients not yet eligible for ART.

Development of a morphometric magnetic resonance image parameter suitable for distinguishing between normal dogs and dogs with cerebellar atrophy

Neurodegenerative diseases affect the cerebellum of numerous dog breeds. Although subjective, magnetic resonance (MR) imaging has been used to detect cerebellar atrophy in these diseases, but there are few data available on the normal size range of the cerebellum relative to other brain regions. The purpose of this study was to determine whether the size of the cerebellum maintains a consistent ratio with other brain regions in different ages and breeds of normal dogs and to define a measurement that can be used to identify cerebellar atrophy on MR images. Images from 52 normal and 13 dogs with cerebellar degenerative diseases were obtained. Volume and mid-sagittal cross-sectional area of the forebrain, brainstem, and cerebellum were calculated for each normal dog and compared between different breeds and ages as absolute and relative values. The ratio of the cerebellum to total brain and of the brainstem to cerebellum mid-sagittal cross-sectional area was compared between normal and affected dogs and the sensitivity and specificity of these ratios at distinguishing normal from affected dogs was calculated. The percentage of the brain occupied by the cerebellum in diverse dog breeds between 1 and 5 years of age was not significantly different, and cerebellar size did not change with increasing age. Using a cut off of 89%, the ratio between the brainstem and cerebellum mid-sagittal cross-sectional area could be used successfully to differentiate affected from unaffected dogs with a sensitivity and specificity of 100%, making this ratio an effective tool for identifying cerebellar atrophy on MR images.

Differences in neointimal thickness between the adluminal and the abluminal sides of malapposed and side-branch struts in a polylactide bioresorbable scaffold: evidence in vivo about the abluminal healing process

The goal of this study was to describe the neointimal healing on the abluminal side (ABL) of malapposed (ISA) struts and nonapposed side-branch (NASB) struts in terms of coverage by optical coherence tomography (OCT) and in comparison with the adluminal side (ADL).

Species-Specific Relationships between Water Transparency and Male Coloration within and between Two Closely Related Lake Victoria Cichlid Species

Environmental variation in signalling conditions affects animal communication traits, with possible consequences for sexual selection and reproductive isolation. Using spectrophotometry, we studied how male coloration within and between populations of two closely related Lake Victoria cichlid species (Pundamilia pundamilia and P. nyererei) covaries with water transparency. Focusing on coloration patches implicated in sexual selection, we predicted that in clear waters, with broad-spectrum light, (1) colours should become more saturated and (2) shift in hue away from the dominant ambient wavelengths, compared to more turbid waters. We found support for these predictions for the red and yellow coloration of P. nyererei but not the blue coloration of P. pundamilia. This may be explained by the species difference in depth distribution, which generates a steeper gradient in visual conditions for P. nyererei compared to P. pundamilia. Alternatively, the importance of male coloration in intraspecific sexual selection may differ between the species. We also found that anal fin spots, that is, the orange spots on male haplochromine anal fins that presumably mimic eggs, covaried with water transparency in a similar way for both species. This is in contrast to the other body regions studied and suggests that, while indeed functioning as signals, these spots may not play a role in species differentiation.

Bone healing and graft resorption of autograft, anorganic bovine bone and beta-tricalcium phosphate. A histologic and histomorphometric study in the mandibles of minipigs

OBJECTIVE: The purpose was to qualitatively and quantitatively compare the bone formation and graft resorption of two different bone substitutes used in both orthopedic and oral surgery, with autogenous bone as a positive control. MATERIALS AND METHODS: Three standardized bone defects were prepared in both mandibular angles of 12 adult minipigs. The defects were grafted with either autograft, anorganic bovine bone (ABB), or synthetic beta-tricalcium phosphate (beta-TCP). Sacrifice was performed after 1, 2, 4, and 8 weeks for histologic and histomorphometric analysis. RESULTS: At 2 weeks, more new bone formation was seen in defects filled with autograft than with ABB (P approximately 0.0005) and beta-TCP (P approximately 0.002). After 4 weeks, there was no significant difference between beta-TCP and the two other materials. Defects grafted with ABB still exhibited less bone formation as compared with autograft (P approximately 0.004). At 8 weeks, more bone formation was observed in defects grafted with autograft (P approximately 0.003) and beta-TCP (P approximately 0.00004) than with ABB. No difference could be demonstrated between beta-TCP and autograft. beta-TCP resorbed almost completely over 8 weeks, whereas ABB remained stable. CONCLUSION: Both bone substitutes seemed to decelerate bone regeneration in the early healing phase as compared with autograft. All defects ultimately regenerated with newly formed bone and a developing bone marrow. The grafting materials showed complete osseous integration. Both bone substitutes may have a place in reconstructive surgery where different clinical indications require differences in biodegradability.

Correlation between the area of increased autofluorescence surrounding geographic atrophy and disease progression in patients with AMD

PURPOSE: To test the hypothesis that the extension of areas with increased fundus autofluorescence (FAF) outside atrophic patches correlates with the rate of spread of geographic atrophy (GA) over time in eyes with age-related macular degeneration (AMD). METHODS: The database of the multicenter longitudinal natural history Fundus Autofluorescence in AMD (FAM) Study was reviewed for patients with GA recruited through the end of August 2003, with follow-up examinations within at least 1 year. Only eyes with sufficient image quality and with diffuse patterns of increased FAF surrounding atrophy were chosen. In standardized digital FAF images (excitation, 488 nm; emission, >500 nm), total size and spread of GA was measured. The convex hull (CH) of increased FAF as the minimum polygon encompassing the entire area of increased FAF surrounding the central atrophic patches was quantified at baseline. Statistical analysis was performed with the Spearman's rank correlation coefficient (rho). RESULTS: Thirty-nine eyes of 32 patients were included (median age, 75.0 years; interquartile range [IQR], 67.8-78.9); median follow-up, 1.87 years; IQR, 1.43-3.37). At baseline, the median total size of atrophy was 7.04 mm2 (IQR, 4.20-9.88). The median size of the CH was 21.47 mm2 (IQR, 15.19-28.26). The median rate of GA progression was 1.72 mm2 per year (IQR, 1.10-2.83). The area of increased FAF around the atrophy (difference between the CH and the total GA size at baseline) showed a positive correlation with GA enlargement over time (rho=0.60; P=0.0002). CONCLUSIONS: FAF characteristics that are not identified by fundus photography or fluorescein angiography may serve as a prognostic determinant in advanced atrophic AMD. As the FAF signal originates from lipofuscin (LF) in postmitotic RPE cells and since increased FAF indicates excessive LF accumulation, these findings would underscore the pathophysiological role of RPE-LF in AMD pathogenesis.

Association between cannabis use and sexual risk behavior among young heterosexual adults

To study the association between cannabis use and frequent sexual risk behavior, we tested the hypothesis of a situational influence of cannabis use in sexual encounters using a combination of global association study and event-level analysis and examined possible mediator variables, including the personality trait of hedonism/risk preference, psychosocial stress, and HIV-related beliefs, using mediation models. The results of a computer-assisted telephone interview of a random sample of 2790 heterosexual men and women aged 16-24 years showed that risky sexual behavior was more frequent in cannabis-using men and women than in non-using persons. The results did not support a situational effect of cannabis intoxication on sexual risk behavior. The more frequent sexual risk behavior among cannabis users was mediated by decreased intentions to use HIV protection, by lower HIV-self-efficacy, and higher risk preference/hedonism. Only among women psychosocial stress was a partial mediator. The findings show that HIV prevention programs for cannabis-using young adults should emphasize the role of person variables instead of situation variables.

A novel quantitative method for analyzing the distributions of nanoparticles between different tissue and intracellular compartments

The penetration, translocation, and distribution of ultrafine and nanoparticles in tissues and cells are challenging issues in aerosol research. This article describes a set of novel quantitative microscopic methods for evaluating particle distributions within sectional images of tissues and cells by addressing the following questions: (1) is the observed distribution of particles between spatial compartments random? (2) Which compartments are preferentially targeted by particles? and (3) Does the observed particle distribution shift between different experimental groups? Each of these questions can be addressed by testing an appropriate null hypothesis. The methods all require observed particle distributions to be estimated by counting the number of particles associated with each defined compartment. For studying preferential labeling of compartments, the size of each of the compartments must also be estimated by counting the number of points of a randomly superimposed test grid that hit the different compartments. The latter provides information about the particle distribution that would be expected if the particles were randomly distributed, that is, the expected number of particles. From these data, we can calculate a relative deposition index (RDI) by dividing the observed number of particles by the expected number of particles. The RDI indicates whether the observed number of particles corresponds to that predicted solely by compartment size (for which RDI = 1). Within one group, the observed and expected particle distributions are compared by chi-squared analysis. The total chi-squared value indicates whether an observed distribution is random. If not, the partial chi-squared values help to identify those compartments that are preferential targets of the particles (RDI > 1). Particle distributions between different groups can be compared in a similar way by contingency table analysis. We first describe the preconditions and the way to implement these methods, then provide three worked examples, and finally discuss the advantages, pitfalls, and limitations of this method.

Resolving the tragedy of the commons: the feedback between intraspecific conflict and population density

Competition and conflict among individuals can favour exploitative strategies that undermine the common good. Theory suggests that this can lead to a tragedy of the commons and ultimately population extinction, a phenomenon known as evolutionary suicide. Here, I present a model of the evolutionary tragedy of the commons that explicitly considers the population dynamics where individuals invest in individually costly competitive traits. In the simplest form, this supports the notion that selection for high levels of conflict can cause evolutionary suicide. However, as competition comes with survival and fecundity costs, a feedback between the investment in competition and population density can act to reduce the level of conflict and prevent the population from going extinct. This suggests that the interaction between population ecology and the evolution of competition and conflict among individuals may be an important mechanism in resolving the level of competition and conflict among individuals.

Surface uplift and climate change - the geomorphic evolution of the western escarpment of the Andes of northern Chile between the Miocene and present

The Western Escarpment of the Andes at 18.30°S (Arica area, northern Chile) is a classical example for a transient state in landscape evolution. This part of the Andes is characterized by the presence of >10,000 km2 plains that formed between the Miocene and the present, and >1500 m deeply incised valleys. Although processes in these valleys scale the rates of landscape evolution, determinations of ages of incision, and more importantly, interpretations of possible controls on valley formation have been controversial. This paper uses morphometric data and observations, stratigraphic information, and estimates of sediment yields for the time interval between ca. 7.5 Ma and present to illustrate that the formation of these valleys was driven by two probably unrelated components. The first component is a phase of base-level lowering with magnitudes of∼300–500 m in the Coastal Cordillera. This period of base-level change in the Arica area, that started at ca. 7.5 Ma according to stratigraphic data, caused the trunk streams to dissect headward into the plains. The headward erosion interpretation is based on the presence of well-defined knickzones in stream profiles and the decrease in valley widths from the coast toward these knickzones. The second component is a change in paleoclimate. This interpretation is based on (1) the increase in the size of the largest alluvial boulders (from dm to m scale) with distal sources during the last 7.5 m.y., and (2) the calculated increase in minimum fluvial incision rates of ∼0.2 mm/yr between ca. 7.5 Ma and 3 Ma to ∼0.3 mm/yr subsequently. These trends suggest an increase in effective water discharge for systems sourced in the Western Cordillera (distal source). During the same time, however, valleys with headwaters in the coastal region (local source) lack any evidence of fluvial incision. This implies that the Coastal Cordillera became hyperarid sometime after 7.5 Ma. Furthermore, between 7.5 Ma and present, the sediment yields have been consistently higher in the catchments with distal sources (∼15 m/m.y.) than in the headwaters of rivers with local sources (<7 m/m.y.). The positive correlation between sediment yields and the altitude of the headwaters (distal versus local sources) seems to reflect the effect of orographic precipitation on surface erosion. It appears that base-level change in the coastal region, in combination with an increase in the orographic effect of precipitation, has controlled the topographic evolution of the northern Chilean Andes.

The 14-bp deletion polymorphism in the HLA-G gene displays significant differences between ulcerative colitis and Crohn's disease and is associated with ileocecal resection in Crohn's disease

HLA-G is a non-classical MHC class Ib molecule predominantly expressed in cytotrophoblasts and under pathological conditions also in chronically inflamed and in malignant tissues. Recently an increased expression of HLA-G was found in ulcerative colitis (UC), but not in Crohn's disease (CD). The HLA-G gene is located in IBD3, a linkage region for inflammatory bowel disease (IBD). A 14-bp deletion polymorphism (Del+/Del-) within exon 8 of the HLA-G gene might influence transcription activity and is therefore of potential functional relevance. To investigate whether the 14-bp deletion polymorphism is associated with IBD, 371 patients with CD, 257 patients with UC and 739 controls were genotyped. The heterozygous genotype (P = 0.031) and the Del+ phenotype (P = 0.038) were significantly increased, whereas the homozygous Del- phenotype (P = 0.038) was significantly decreased in UC when compared with CD. Thus, the 14-bp deletion polymorphism within the HLA-G gene displayed significant differences between UC and CD. Moreover, a significant increase of the Del+ allele (P = 0.002) and the Del+/Del+ genotype (P = 0.013) and a consecutive decrease of the Del-/- genotype (P = 0.024) were observed in those CD cases positive for ileocecal resection. Thus, a potential effect of the HLA-G gene in IBD may affect both UC and CD. Other polymorphisms linked to the 14-bp deletion polymorphism might also contribute to immunopathogenesis. As there are several partly functional polymorphisms within the promoter region potentially influencing HLA-G expression, further studies in IBD are necessary in the context of differential expression of HLA-G between UC and CD.

Stability of the hard and soft tissue profile after mandibular advancement in sagittal split osteotomies: a longitudinal and long-term follow-up study

The aim of the study was to conduct a long-term follow-up investigation of the stability of hard and soft tissues after bilateral sagittal split osteotomy (BSSO) with rigid internal (RIF) fixation to advance the mandible. Sixteen consecutive patients (12 females and 4 males, mean age 21.4 years) were available for re-examination 12.7 years (T5) after surgery. The preceding follow-ups were before (T1), and 5 days (T2), 7.3 months (T3), and 13.9 months (T4) after surgery. Lateral cephalograms were traced by hand, digitized, and evaluated with the Dentofacial Planner program. The x-axis for the system of co-ordinates ran through sella (point zero) and the line NSL -7 degrees. Thus, the program determined the x- and y-values of each variable and the usual angles and distances. Statistical analysis was carried out using Wilcoxon's matched-pair signed-ranks test with Bonferroni adjustments. The relationships between the examined variables were analysed by Spearman rank correlation coefficients. The backward relapse at point B (T5) was 2.42 mm, or 50 per cent, and at pogonion 3.21 mm, or 60 per cent of the initial advancement. The mean net effect at T5 on the labial fold (soft tissue point B) was 94 per cent of the advancement at point B. For the soft tissue chin (soft tissue pogonion), it was 119 per cent of the advancement at pogonion. The net effect on the lower lip (labrale inferior) was 55 per cent of the advancement at incision inferior. The amount of the surgical advancement of the mandible was correlated with the long-term relapse in point B. Among possible reasons for this relapse are the initial soft tissue profile, the initial growth direction, and the remodelling processes of the hard tissue.