Chronic HIV-2 infection protects against total CD4+ cell depletion and rapid disease progression induced by SHIV89.6p challenge

OBJECTIVE: To better understand HIV-1 sexual transmission risk, we have studied the susceptibility of HIV-2-exposed, uninfected (EU) female pig-tailed macaques to intravaginal (IVAG) re-challenge with the homologous HIV-2 strain, followed by heterologous SHIV89.6p. METHODS: Nine female macaques, previously protected by a post-exposure prophylaxis (PEP) regimen, along with one mock-treated EU animal, were re-exposed to HIV-2 by the IVAG route approximately 1.5 years later. A single follow-up challenge was performed approximately 1 year later with SHIV89.6p to assess susceptibility of chronic HIV-2-infected animals to further re-infection and pathogenic effects with a heterologous virus, somewhat mimicking HIV-1. RESULTS: Eight of ten macaques (80%) became infected systemically with HIV-2, and plasma or cervicovaginal vRNA levels did not appreciably differ from prior historic non-PEP control macaques. Interestingly, all eight HIV-2-infected females were susceptible to SHIV89.6p infection by either intravenous (n = 4) or IVAG exposure (n = 4) after one inoculation. Plasma vRNA levels in these groups were controlled by week 8 and there were no decrease in CD4+ T cells > 50%. The remaining two HIV-2 EU macaques, inoculated intrarectally with SHIV89.6p, were unable to control virus replication and succumbed to disease by week 25 or week 61. CONCLUSIONS: Our findings demonstrate that successful PEP regimens to prevent an initial infection do not have any lasting protective effects. The observed lack of cross-protection against SHIV89.6p transmission among chronic HIV-2-infected macaques provides modeling support for limited epidemiologic data indicating that human HIV-2 infection does not protect against HIV-1 infection, but may serve to alter overt clinical outcome.     

Clinical, angiographic, and intravascular ultrasound characteristics of early saphenous vein graft failure

OBJECTIVES: We sought to examine saphenous vein graft (SVG) lesions that fail within the first year after operation. BACKGROUND: Saphenous vein grafts remain patent for approximately 10 years; however, up to 15% to 20% of SVGs become occluded within the first year. METHODS: We studied 100 patients who underwent percutaneous coronary intervention (PCI) for early (<1 year post-implantation) SVG failure lesions and compared them with a diabetes- and hypercholesterolemia-matched cohort of late SVG failures (>1 year). Coronary angiography and intravascular ultrasound images were analyzed. RESULTS: The majority of patients in both groups were males who presented with unstable angina; 36% were diabetic. Graft ages were 6.0 +/- 2.9 months and 105.4 +/- 50.8 months, respectively. The early SVG failure lesion location was more often ostial or proximal (62% vs. 42%, respectively). Early SVG failures were angiographically smaller than late failures (reference: 2.47 +/- 0.86 mm vs. 3.26 +/- 0.83 mm, p < 0.001) but had similar lesion lengths. Intravascular ultrasound showed that early failure lesions had smaller proximal and distal reference lumen areas (7.3 +/- 6.8 mm2 vs. 10.6 +/- 3.8 mm2, p = 0.026) and greater reference plaque burden than late failures (52.3% vs. 36.1%, p < 0.001). After PCI, 20.6% of early and 30.6% of late failure lesions had creatine kinase-myocardial band (CK-MB) greater than twice normal. CONCLUSIONS: Early SVG failure is mostly proximal or ostial, lesions appear focal, and early SVGs appear smaller than late SVGs. Intravascular ultrasound shows significant reference segment plaque burden, suggesting more severe, diffuse SVG disease.     

A comparison of biventricular and conventional transvenous defibrillation: a computational study using patient derived models

Conventional transvenous defibrillation is performed with an ICD using a dual current pathway. The defibrillation energy is delivered from the RV electrode to the superior vena cava (SVC) electrode and the metallic case (CAN) of the ICD. Biventricular defibrillation uses an additional electrode placed in the LV free wall with sequential shocks to create an additional current vector. Clinical studies of biventricular defibrillation have reported a 45% reduction in mean defibrillation threshold (DFT) energy. The aim of the study was to use computational methods to examine the biventricular defibrillation fields together with their corresponding DFTs in a variety of patient derived models and to compare them to simulations of conventional defibrillation. A library of thoracic models derived from nine patients was used to solve for electric field distributions. The defibrillation waveform consisted of a LV --> SVC + CAN monophasic shock followed by a biphasic shock delivered via the RV --> SVC + CAN electrodes. When the initial voltage of the two shocks is the same, the simulations show that the biventricular configuration reduces the mean DFT by 46% (3.5 +/- 1.3 vs 5.5 +/- 2.7 J, P = 0.005). When the leading edge of the biphasic shock is equal to the trailing edge of the monophasic shock, there is no statistically significant difference in the mean DFT (4.9 +/- 1.9 vs 5.5 +/- 2.7 J, P > 0.05) with the DFT decreasing in some patients and increasing in others. These results suggest that patient-specific computational models may be able to identify those patients who would most benefit from a biventricular configuration.     

Acquired brain injury, visual attention, and the useful field of view test: A pilot study

OBJECTIVE: To compare the findings of the Useful Field of View (UFOV) test with those of conventional neuropsychologic tests to determine the utility of the UFOV test as a measure of attention in a population with brain injury. DESIGN: Cohort study. SETTING: Freestanding rehabilitation hospital. PARTICIPANTS: Fifteen inpatients with severe brain injury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: UFOV test, FIM\T instrument, length of stay (LOS), and standard neuropsychologic testing. RESULTS: The UFOV subtest UF2 correlated strongly with the other 2 subtests, UF1 and UF3. The UF2 subtest correlated most strongly with paper and pencil tests of visual attention. The UF2 predicted 52% of the FIM change and 60% of the LOS variance, second only to admission FIM score, which predicted 75% and 80% of FIM change and LOS variance, respectively. CONCLUSIONS: Among the patients in our study, the UFOV test can be used to determine the visual divided attention of patients with acquired brain injury. The results also showed that the UFOV test correlated with LOS and FIM change in patients with acquired brain injury recovering in a rehabilitation facility. Because the UFOV test is much more quickly administered and scored than other measures of attention and divided attention, these results suggest that the UFOV test may provide an easy means to measure a critical variable in the population with head injury.     

Immune phenomena involved in the in vivo regression of fibrosarcoma cells expressing cell-associated IL-1alpha

Constitutive expression of cell-associated, but not secreted, interleukin-1alpha (IL-1alpha) by oncogene-transformed fibrosarcoma cells induced regressing tumors in mice, a phenomenon that was abrogated by the IL-1 inhibitor, the IL-1 receptor antagonist (IL-1Ra). On the contrary, non-IL-1alpha-expressing tumor cells induce progressive tumors in mice. In vivo and ex vivo experiments have shown that regression of IL-1alpha-positive fibrosarcoma cells depends on CD8(+) T cells, which can also be activated in CD4(+) T cell-depleted mice, with some contribution of natural killer cells. In spleens of mice bearing the non-IL-1alpha-expressing fibrosarcoma cells, some early and transient manifestations of antitumor-specific immunity, such as activation of specific proliferating T cells, are evident; however, no development of cytolytic T lymphocytes or other antitumor protective cells could be detected. In spleens of mice bearing the non-IL-1alpha-expressing fibrosarcoma cells, the development of early tumor-mediated suppression was observed, and in spleens of mice injected with IL-1alpha-positive fibrosarcoma cells, protective immunity developed in parallel to tumor regression. Treatment of mice bearing violent fibrosarcoma tumors with syngeneic-inactivated, IL-1alpha-positive fibrosarcoma cells, at a critical interval after injection of the malignant cells (Days 5-12), induced tumor regression, possibly by potentiating and amplifying transient antitumor cell immune responses or by ablation of tumor-mediated suppression. Membrane-associated IL-1alpha may thus serve as an adhesion molecule, which allows efficient cell-to-cell interactions between the malignant and immune effector cells that bear IL-1Rs and function as a focused cytokine with adjuvant activities at nontoxic, low levels of expression. Our results also point to the potential of using antitumor immunotherapeutic approaches using cell-associated IL-1alpha.     

Development of an automated individual tree detection model using point cloud LiDAR data for accurate tree counts in a Pinus radiata plantation

We develop and evaluate a new individual tree detection (ITD) algorithm to automatically locate and estimate the number of individual trees within a Pinus radiata plantation from relatively sparse airborne LiDAR point cloud data. The area of interest comprised stands covering a range of age classes and stocking levels. Our approach is based on local maxima (LM) filtering that tackles the issue of selecting the optimal search radius from the LiDAR point cloud for every potential LM using metrics derived from local neighbourhood data points; thus, it adapts to the local conditions, irrespective of canopy variability. This was achieved through two steps: (i) logistic regression model development using simulated stands composed of individual trees derived from real LiDAR point cloud data and (ii) application testing of the model using real plantation LiDAR point cloud data and geolocated, tree-level reference crowns that were manually identified in the LiDAR imagery. Our ITD algorithm performed well compared with previous studies, producing RMSE of 5.7% and a bias of only ?2.4%. Finally, we suggest that the ITD algorithm can be used for accurately estimating stocking and tree mapping, which in turn could be used to derive the plot-level metrics for an area-based approach for enhancing estimates of stand-level inventory attributes based on plot imputation.     

Model‐Predicted Performance of Second‐Trimester Down Syndrome Screening With Sonographic Prenasal Thickness

Objective. The purpose of this study was to estimate the Down syndrome detection and false‐positive rates for second‐trimester sonographic prenasal thickness (PT) measurement alone and in combination with other markers. Methods. Multivariate log Gaussian modeling was performed using numerical integration. Parameters for the PT distribution, in multiples of the normal gestation‐specific median (MoM), were derived from 105 Down syndrome and 1385 unaffected pregnancies scanned at 14 to 27 weeks. The data included a new series of 25 cases and 535 controls combined with 4 previously published series. The means were estimated by the median and the SDs by the 10th to 90th range divided by 2.563. Parameters for other markers were obtained from the literature. Results. A log Gaussian model fitted the distribution of PT values well in Down syndrome and unaffected pregnancies. The distribution parameters were as follows: Down syndrome, mean, 1.334 MoM; log₁₀ SD, 0.0772; unaffected pregnancies, 0.995 and 0.0752, respectively. The model‐predicted detection rates for 1%, 3%, and 5% false‐positive rates for PT alone were 35%, 51%, and 60%, respectively. The addition of PT to a 4–serum marker protocol increased detection by 14% to 18% compared with serum alone. The simultaneous sonographic measurement of PT and nasal bone length increased detection by 19% to 26%, and with a third sonographic marker, nuchal skin fold, performance was comparable with first‐trimester protocols. Conclusions. Second‐trimester screening with sonographic PT and serum markers is predicted to have a high detection rate, and further sonographic markers could perform comparably with first‐trimester screening protocols.