Systematic review of the efficacy and safety of biological therapy for inflammatory conditions in HIV-infected individuals

Biologic therapies are injectable immunomodulatory agents directed against specific immune cell or chemical targets. They have transformed the lives of HIV-uninfected individuals with severe inflammatory conditions including psoriasis, rheumatoid arthritis, and ulcerative colitis. The perceived increased infection risk associated with these agents means that HIV-infected individuals have not been included in randomised control trials of these drugs. The literature for use of biologic therapies in HIV-infected populations is limited to case reports and case series. There are additional data on use of rituximab, a monoclonal antibody against B lymphocytes, in the setting of HIV-associated haematological malignancy. We performed a systematic review of efficacy and safety of biologic therapy for inflammatory conditions in HIV-infected individuals. Our systematic review identified 37 treatment episodes with six different biologic agents encompassing 10 different inflammatory conditions. Broadly, efficacy of the agents studied was comparable to reports from HIV-uninfected patients. Both infectious and non-infectious sequelae were also comparable with trial data from HIV-uninfected patients. HIV control, even for the minority of individuals not receiving anti-retroviral therapy (ART) at the time of biologic therapy, was not adversely affected. However, detail was limited concerning ART regimens and both immunological and virological parameters of follow-up. Overall available literature is of very low quality and likely subject to publication bias of successful cases. Firm conclusions are not possible regarding the efficacy and safety of biologic agents in HIV-infected individuals; however, there appear to be sufficient data to warrant inclusion of individuals with well-controlled HIV in future trial studies

Artificial Shelters And Survival Of Juvenile Caribbean Spiny Lobster Panulirus-Argus - Spatial, Habitat, And Lobster Size Effects

A principal mechanism underlying a production hypothesis that artifical reefs increase environmental carrying capacity and eventually the biomass of reef-associated organisms is that these structures reduce predation on reef residents. We tested this predation mechanism with a series of field experiments at two sites (inner-bay sand-seagrass flat, and outer-bay seagrass bed adjacent to coral reefs) in Bahia de la Ascension, Mexico. We examined survival of two size-classes of juvenile Caribbean spiny lobster Panulirus argus tethered in seagrass beds with and without access to artificial lobster shelters, and at different distances from the shelters. The artificial shelters were concrete structures (casitas) that simulate lobster dens. Large juvenile lobsters (56-65 mm CL) attained a relative size refuge when tethered 60 m away from casitas compared with smaller (46-55 mm CL) lobsters. Conversely, the small lobsters survived better beneath casitas than did large lobsters. Small juveniles also survived better at casitas or 30 m away from casitas than at 15 m or 70 m away. Observations indicated that the daytime predator guild, composed primarily of snappers (family Lutjanidae), seldom foraged more than 60 m from casitas and were typically within 15 m of casitas. There was also a significant positive correlation between predation-induced lobster mortality and numbers of snapper associated with casitas at the inner-bay site. Thus, tethering lobsters 70 m away from casitas appeared adequate to examine survival of lobsters in an environment uninfluenced by daytime predators aggregating to casitas. These results indicate that (1) the relative importance of a lobster-size refuge from predators varies according to shelter availability, and (2) that there is a nonlinear relationship between predation risk and distance from an artifical shelter. Our results demonstrate that casitas increase survival of small juvenile lobsters but reduce survival of larger juveniles. Small casitas scaled according to body size may enhance survival of large juvenile lobsters in nursery habitats where large conspecifics are removed from large casitas

Histological Observation of Islet Hemorrhage Induced by Diagnostic Ultrasound with Contrast Agent in Rat Pancreas

Contrast enhanced diagnostic ultrasound CEDUS has been shown to induce capillary hemorrhage in heart and kidney. This study characterized the capillary hemorrhage induced in rat pancreas. The pancreata of anesthetized hairless rats were accessed by laparotomy. A 1.5 MHz diagnostic ultrasound probe with 2.3 MPa peak rarefactional pressure amplitude and 1 s intermittent trigger was used to scan the pancreas, located at the focus (3.8 cm), through saline coupling. The probe was swept to expose the entire organ in 5 min during infusion of Definity® contrast agent at 10 µL/kg/min, and this was repeated in a reverse sweep. The entire pancreas was removed, spread flat for fixation and histological slides were prepared from the mid-plane. Slides were scored blind for islet hemorrhage over the entire area of the organ. Intra-islet microlesions were evident and hemorrhage surrounded many islets. The hemorrhage often impacted nearby acini, and expanded into inter-lobular septa. In CEDUS pancreata removed soon after scanning, 76.2±11.8% (n = 6) of islets had evidence of hemorrhage and/or islet microlesions compared to 1.1±2.5% (n = 5) for sham CEDUS (P<0.001). In pancreata removed after 4 hr, fibrin formation was detected by immunohistology in the hemorrhage and intra-islet microlesions. Diagnostic ultrasound with contrast agent induced substantial capillary hemorrhage in rat pancreas, concentrated particularly in the islets

Methods for measuring fluoroscopic skin dose

This paper briefly reviews available technologies for measuring or estimating patient skin dose in the interventional fluoroscopic environment

Acceptance Criteria for Critical Software Based on Testability Estimates and Test Results

Testability is defined as the probability that a program will fail a test, conditional on the program containing some fault. In this paper, we show that statements about the testability of a program can be more simply described in terms of assumptions on the probability distribution of the failure intensity of the program. We can thus state general acceptance conditions in clear mathematical terms using Bayesian inference. We develop two scenarios, one for software for which the reliability requirements are that the software must be completely fault-free, and another for requirements stated as an upper bound on the acceptable failure probability

Reliable microsatellite genotyping of the Eurasian badger (Meles meles) using faecal DNA

The potential link between badgers and bovine tuberculosis has made it vital to develop accurate techniques to census badgers. Here we investigate the potential of using genetic profiles obtained from faecal DNA as a basis for population size estimation. After trialling several methods we obtained a high amplification success rate (89%) by storing faeces in 70% ethanol and using the guanidine thiocyanate/silica method for extraction. Using 70% ethanol as a storage agent had the advantage of it being an antiseptic. In order to obtain reliable genotypes with fewer amplification reactions than the standard multiple-tubes approach, we devised a comparative approach in which genetic profiles were compared and replication directed at similar, but not identical, genotypes. This modified method achieved a reduction in polymerase chain reactions comparable with the maximumlikelihood model when just using reliability criteria, and was slightly better when using reliability criteria with the additional proviso that alleles must be observed twice to be considered reliable. Our comparative approach would be best suited for studies that include multiple faeces from each individual. We utilized our approach in a well-studied population of badgers from which individuals had been sampled and reliable genotypes obtained. In a study of 53 faeces sampled from three social groups over 10 days, we found that direct enumeration could not be used to estimate population size, but that the application of mark–recapture models has the potential to provide more accurate results

Mixture models for distance sampling detection functions

Funding: EPSRC DTGWe present a new class of models for the detection function in distance sampling surveys of wildlife populations, based on finite mixtures of simple parametric key functions such as the half-normal. The models share many of the features of the widely-used “key function plus series adjustment” (K+A) formulation: they are flexible, produce plausible shapes with a small number of parameters, allow incorporation of covariates in addition to distance and can be fitted using maximum likelihood. One important advantage over the K+A approach is that the mixtures are automatically monotonic non-increasing and non-negative, so constrained optimization is not required to ensure distance sampling assumptions are honoured. We compare the mixture formulation to the K+A approach using simulations to evaluate its applicability in a wide set of challenging situations. We also re-analyze four previously problematic real-world case studies. We find mixtures outperform K+A methods in many cases, particularly spiked line transect data (i.e., where detectability drops rapidly at small distances) and larger sample sizes. We recommend that current standard model selection methods for distance sampling detection functions are extended to include mixture models in the candidate set.Publisher PDFPeer reviewe